Abstract:Suzi Jiangqitang is one of the classical formulas in the Catalogue of Ancient Classical Formulas （the second batch）—Han Medicine. The research method of philology was employed to systematically review the ancient documents and modern medical reports of Suzi Jiangqitang. The key information of this formula， including origin， composition， compatibility， original plants， processing method， dosage， preparation method， usage， and indications， was summarized to provide literature and data support for the development and clinical application of this formula. Suzi Jiangqitang is originally known as Zusuzi Tang， which is derived from Important Prescriptions Worth a Thousand Gold for Emergency. This formula is composed of Perillae Fructus， Pinelliae Rhizoma， Peucedani Radix， Magnoliae Officinalis Cortex， Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Citri Reticulatae Pericarpium， Perillae Folium， Jujubae Fructus， Zingiberis Rhizoma Recens， and Cinnamomi Cortex. The original plants of other herbal medicines except Peucedani Radix follow those in the 2020 edition of Pharmacopoeia of the People's Republic of China. Raw materials of Angelicae Sinensis Radix， Peucedani Radix， Cinnamomi Cortex， Citri Reticulatae Pericarpium， Perillae Folium， and Jujubae Fructus are used in this formula. Perillae Fructus， Pinelliae Rhizoma， Glycyrrhizae Radix et Rhizoma， and Magnoliae Officinalis Cortex in this formula are stir-fried， processed with alumen， stir-fried， and processed with ginger， respectively， and the fresh material of Zingiberis Rhizoma Recens is used in this formula. The recommended formula is composed of 15 g Perillae Fructus， 15 g Pinelliae Rhizoma， 6 g Angelicae Sinensis Radix， 6 g Glycyrrhizae Radix et Rhizoma， 6 g Peucedani Radix， 6 g Magnoliae Officinalis Cortex， 9 g Cinnamomi Cortex， and 9 g Citri Reticulatae Pericarpium. On the basis of the recommended dosage， other herbal medicines are crushed and mixed with five pieces of Perillae Folium， one jujube， and two ginger pieces. The mixture should be decocted in 450 mL water to reach a volume of 240 mL. After removal of the residue， the decoction should be taken warm with no time limitation. In ancient times， Suzi Jiangqitang was most commonly used to treat dermatophytosis， dyspnea with cough， red eyes， blood syndrome， globus hysteriocus， and headache. In modern times， it is commonly used for treating respiratory diseases， especially chronic obstructive pulmonary disease and dyspnea with cough. In addition， this formula is used to treat circulatory and digestive diseases， such as pulmonary heart disease， constipation， and vomiting. It is also used to treat globus hysteriocus and blood syndrome. Although the range of indications is wide， the diseases treated by Suzi Jiangqitang are generally caused by excess in the upper， deficiency in the lower， and failure of Qi to ascend or descend.

Abstract:Guizhi Mahuang Geban Tang derived from ZHANG Zhongjing's Treatise on Cold Damage is included in the Catalogue of Ancient Classic formulas （the second batch） issued by the National Administration of Traditional Chinese Medicine. By reviewing the ancient literature related to Guizhi Mahuang Geban Tang， this study analyzed the origin， medicinal composition， original plants and processing， dosage， decocting method， compatibility， effects， and indications of this formula. A total of 186 records of Guizhi Mahuang Geban Tang were obtained， involving 108 ancient books of traditional Chinese medicine. There are 6 synonyms of Guizhi Mahuang Geban Tang. This formula consists of Cinnamomi Ramulus， Paeoniae Radix Alba， Zingiberis Rhizoma Recens， Glycyrrhizae Radix et Rhizoma， Ephedrae Herba， Jujubae Fructus， and Armeniacae Semen Amarum， the original plants and processing of which are clear. With consideration to the dosage in modern clinical practice， it is recommended that the formula should be composed of 7.67 g Cinnamomi Ramulus， 4.60 g Paeoniae Radix Alba， 4.60 g Zingiberis Rhizoma Recens， 4.60 g Glycyrrhizae Radix et Rhizoma， 4.60 g Ephedrae Herba， 4.00 g Jujubae Fructus， and 2.60 g Armeniacae Semen Amarum. The decoction should be prepared by boiling Ephedrae Herba with 1 000 mL water for 15 min before the addition of other medicines， and the mixture was decocted to reach a volume of 360 mL， and 120 mL of the decoction should be taken warm once. Guizhi Mahuang Geban Tang is a combination of Guizhi Tang and Mahuang Tang， with the effects of dispersing wind cold and harmonizing nutrient-defense. The main diseases treated by this formula in the past dynasties have expanded compared with those in Treatise on Cold Damage. The traditional indications of this formula involve the diseases of greater Yang， reverting Yin， Yang brightness， and lesser Yin. In addition to common cold due to wind-cold， this formula can be used to treat headache， bitter mouth， dry throat， full abdomen， panting， heat invading blood chamber in women， skin itching， exanthema variolosum， syncope， and hardly perceivable pulse. In modern clinical practice， Guizhi Mahuang Geban Tang is used for treating pulmonary diseases such as upper respiratory tract infection， skin diseases （e.g.， urticaria， eczema， psoriasis， and neurodermatitis）， kidney failure， and diabetes complicated with pruritus.

Abstract:Objective To analyze the current research status of the classical formulas in China and predict the future development trends， thus providing reference and suggestions for the scientific research and clinical application of classical formulas.Method The relevant publications were retrieved from China National Knowledge Infrastructure （CNKI） with the time interval from January 1， 2008 to August 1， 2023， and the publications were counted. CiteSpace 6.1.R6 was used for visual analysis of the authors， research institutions， and keywords.Result A total of 847 valid publications were included in this study. The annual number of publications showed a rapid rise after 2018. The Chinese Journal of Experimental Traditional Medical Formulae was the main journal publishing the articles about ancient classical formulas in China. ZHAN Zhilai， BAI Jie， LU Tulin， FU Chaomei， and CHEN Renshou were active researchers in this field and had formed stable research teams. The China Academy of Chinese Medical Sciences and its affiliated institutions published the most articles and had close cooperation with other research institutions in China. The co-occurrence network and cluster map of keywords showed that textual research on materia medica， clinical application， quality standard， fingerprint， and mechanism of action were the core keywords. The top 3 bursts in this field were benchmark samples， quality evaluation， and origin.Conclusion The current research on ancient classical formulas still has shortcomings such as lack of large-scale cooperation between teams and weak transformation of research achievements. At present， the research hotspots in this field mainly include textural research on key information， quality control and fingerprinting， and clinical application. The future research in this field mainly focus on benchmark samples of classical formula preparations， quality evaluation of medicinal materials， pharmacodynamic material basis， and mechanisms of classical formulas.

Abstract:Objective To explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis.Method Fifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18.Result Compared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue.Conclusion Huanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

Abstract:Objective To validate the efficacy of Yunpi Huatan Tongqiao prescription （YHTP） in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea （OSA） mice.Method Forty-eight male Balb/C mice were randomly divided into a normal group， a model group， a montelukast sodium group （30 mg·kg^-1）， and low， medium， and high dose groups of YHTP （8.28， 16.56， and 33.12 g·kg^-1）， with 8 mice in each group. All groups， except the normal group， received intraperitoneal injections of lipopolysaccharide （LPS） and underwent chronic intermittent hypoxia （CIH） modeling for 4 weeks. Subsequently， the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and markers such as T lymphocyte activation antigen （CD86） and inducible nitric oxide synthase （iNOS）， as well as M2-associated inflammatory factors interleukin-10 （IL-10）， transforming growth factor-β （TGF-β）， and the marker mannose receptor （CD206） in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers （CD86， CD206） and glycolysis-related proteins glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phosphofructokinase （PFKM）， pyruvate kinase 2 （PKM2）， and monocarboxylic acid transporter 1 （MCT1）.Result Behavioral tests showed that compared to the results in the normal group， the Y-maze autonomous alternation rate was significantly reduced in the model group （P<0.01）. The latency time for the target hole in the Barnes' maze during the training period （days 2， 3， 4） and testing period （days 5， 12） was significantly increased （P<0.05， P<0.01）. M1 glial cell markers CD86 and iNOS， as well as inflammatory factors IL-1β and TNF-α mRNA， were significantly elevated （P<0.01）. In contrast， the mRNA expression of M2 glial cell markers IL-10， CD206， and TGF-β was significantly reduced （P<0.01）. The protein expression of glycolytic proteins HK2， PFKM， PKM2， MCT1， and the M1 marker CD86 was significantly increased （P<0.05， P<0.01）， while M2 marker CD206 protein expression was significantly decreased （P<0.01）. Compared to the results in the model group， the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP （P<0.05， P<0.01）. The latency time for the target hole during the training （day 4） and testing periods （days 5， 12） was significantly reduced （P<0.01）. Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low， medium， and high dose groups of YHTP （P<0.01）， while M2-related inflammatory factors' mRNA expression was significantly increased （P<0.01）. Western blot results showed that in the medium and high dose groups of YHTP， the expression of the M1 marker CD86 in the hippocampus was reduced， whereas the expression of the M2 marker CD206 was significantly increased （P<0.01）， with a significant decrease in the expression of glycolysis-related proteins （P<0.01）.Conclusion YHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia， inhibiting M1 activation， reducing pro-inflammatory factor release， and promoting M2 activation， thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.

Abstract:Objective To investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis （PMOP） by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and inhibiting excessive autophagy.Method Female SD rats were ovariectomized and randomly divided into the sham operation group （Sham）， the operation group （OVX）， the Ershiwuwei Guijiu pill （GJ） group， and the raloxifene hydrochloride （RLX） group， with 10 rats in each group. Enzyme-linked immunosorbent assay （ELISA） and colorimetric methods were used to detect the levels of estrogen， bone metabolism markers in serum， and total superoxide dismutase （T-SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in tibial tissue. Flow cytometry was used to detect reactive oxygen species （ROS） levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia， and micro-computed tomography （Micro-CT） was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of autophagy-related proteins Beclin1， microtubule-associated protein 1A/1B-light chain 3 （LC3）， autophagy-related 5 （Atg5）， as well as PI3K， Akt， and mTOR in tibial tissue.Result Compared with the Sham group， the OVX group showed a significant decrease in serum levels of estradiol （E₂） and calcium ion （Ca²⁺）， and T-SOD， GSH-Px， PI3K， Akt， and mTOR mRNA levels in bone tissue （P<0.05， P<0.01）， significantly reduced bone mineral density （BMD）， bone surface/bone volume （BS/BV）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular connectivity （Con） in the tibia （P<0.05， P<0.01）， thinner epiphyseal growth plate， and the bone marrow cavity filled with fat vacuoles. Moreover， the levels of phosphorus （P）， MDA， ROS， and mRNA and protein expression of Beclin1， LC3， and Atg5， as well as trabecular separation （Tb.Sp） were significantly elevated （P<0.05， P<0.01）. Compared with the OVX group， the GJ and RLX groups showed significant increases in serum E₂ and Ca²⁺， and bone tissue levels of SOD， GSH-Px， and the mRNA levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）， significantly increased BMD， BS/BV， Tb.Th， Tb.N， and Con in the tibia， thickened epiphyseal growth plate， and significantly reduced fat vacuoles in the bone marrow cavity （P<0.05， P<0.01）. Additionally， the levels of P， MDA， ROS， Beclin1， LC3， Atg5 mRNA and proteins， and Tb.Sp were significantly decreased （P<0.05， P<0.01）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR， which were significantly reduced in the OVX group （P<0.01）， were significantly increased in the GJ and RLX groups （P<0.01）.Conclusion The Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy， thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway， which inhibits autophagy.

Abstract:Objective To study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI.Method Seventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg^-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg^-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot.Result Compared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）.Conclusion Huangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.

Abstract:Objective To explore the mechanism of Cangxi Tongbi capsules （CXTB） in regulating the p38 mitogen-activated protein kinase （p38 MAPK）/NOD-like receptor protein 3 （NLRP3）/cysteine protease-1 （Caspase-1） signaling pathway to inhibit pyroptosis of cartilage cells in knee osteoarthritis （KOA）.Method Sixty male SD rats were randomly divided into a sham operation group， a model group， low， medium， and high dose CXTB groups， and a positive control group， with 10 rats per group. The modified Hulth method was employed to establish a rat model of KOA. According to their respective assignments， rats were administered CXTB （0.25， 0.5， 1.0 g·kg^-1） and Celecoxib （24 mg·kg^-1） by gavage. The sham operation and model groups were given an equivalent volume of physiological saline. Treatment was performed once daily for 28 days. Micro-computed tomography （Micro-CT） was used to assess bone volume/total volume （BV/TV） and trabecular separation （Tb.Sp）. Joint degeneration was evaluated through hematoxylin-eosin （HE） staining， safranin-fast green （SO） staining， and Osteoarthritis Research Society International （OARSI） scoring. Western blot analysis was conducted to measure the expression levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， NLRP3， Caspase-1， and gasdermin D （GSDMD） proteins. Real-time PCR was used to assess mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD genes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum concentrations of inflammatory cytokines including tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， and interleukin-18 （IL-18）. After knee replacement surgery， cartilage tissue was analyzed using Western blot to assess the protein expression levels of p38 MAPK， p-p38 MAPK， NLRP3， Caspase-1， and GSDMD， and Real-time PCR was used to evaluate gene expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD.Result Micro-CT analysis revealed significant narrowing of the joint space and increased bone spur formation in KOA rats compared with the sham operation group， with a decrease in BV/TV ratio and an increase in Tb.Sp value （P<0.01）. Serum levels of TNF-α， IL-1β， and IL-18 were elevated （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD in cartilage were significantly increased （P<0.01）， and the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also enhanced （P<0.01）. Significant differences in protein expression of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were observed between normal and diseased cartilage tissues after knee replacement surgery （P<0.05）， and the gene expression of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also significantly different （P<0.01）. HE and SO staining showed roughened joint surfaces， reduced cartilage thickness， and disordered cellular arrangement in KOA rats. OARSI scores were significantly higher （P<0.01）. Compared with the model group， treatment with low， medium， and high concentrations of CXTB resulted in increased BV/TV ratios and decreased Tb.Sp values in the knee joints of rats （P<0.01）. HE and SO staining indicated a trend towards smoother joint surfaces and reduced OARSI scores （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were notably decreased （P<0.05）， as were the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD （P<0.01）. Additionally， serum concentrations of TNF-α， IL-1β， and IL-18 were significantly reduced （P<0.01）.Conclusion CXTB intervention may alleviate knee joint degeneration in KOA rats and inhibit the expression of inflammatory factors and pyroptosis of cartilage cells， thereby protecting cartilage. The underlying mechanism may involve modulation of the p38 MAPK/NLRP3/Caspase-1 signaling pathway.

Abstract:Objective To systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene".Method Putative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot.Result A total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）.Conclusion HBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.

Abstract:Objective To explore the potential mechanism of Qiling prescription in intervening in chronic atrophic gastritis with gastric intestinal metaplasia （GIM）.Method The 80 SPF-grade SD rats were randomly divided into the following eight groups （10 rats per group）： blank group， blank + Qiling prescription group， model group， high-dose Qiling prescription group， medium-dose Qiling prescription group， low-dose Qiling prescription group， folic acid group， and morodan group. Except for the blank and blank + Qiling prescription groups， the other groups underwent modeling by intragastric administration of 0.02 mol·L^-1 N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） solution combined with irregular feeding. After successful modeling， the blank and model groups were given distilled water， the blank + Qiling prescription group， and high， medium， and low-dose Qiling prescription groups were given Qiling prescription water decoction at 7.60， 15.21， 7.60， 3.80 g·kg^-1， respectively， the folic acid group was given folic acid suspension at 0.002 g·kg^-1， the morodan group was given morodan suspension at 1.40 g·kg^-1 by gavage once a day for 8 weeks. The general condition and body weight of the rats were observed during the experiment. Hematoxylin-eosin （HE） staining was performed on gastric tissues. Immunohistochemistry （IHC） was used to detect the levels of mucin 2 （MUC2） and caudal-type homeobox transcription factor 2 （CDX2） in gastric tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， cysteine-aspartic protease-3 （Caspase-3）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot analysis was performed to detect the expression and phosphorylation levels of PI3K and Akt in gastric tissues.Result Animal experiments showed that compared to the blank group， the rats in the model group had a trend of weight loss starting from week 16. Compared to the model group， high and medium doses of Qiling prescription improved the mental state and body weight of the rats. Pathological results at week 24 showed successful modeling with reduced gastric mucosal glandular cells and disordered arrangement in the model group compared to the blank group. The high and medium-dose Qiling prescription groups showed significantly fewer or absent goblet cells， indicating improved gastric mucosal pathology as compared to model group. Compared to blank group， the model group showed increased levels of MUC2 and CDX2 in gastric tissues （P<0.01）. High and medium doses of Qiling prescription significantly reduced the levels of MUC2 and CDX2 in gastric tissues compared to the model group （P<0.05，P<0.01）. Compared to the blank group， the model group had increased serum levels of IL-6， IL-1β， TNF-α， Caspase-3， PI3K， and Akt （P<0.05）. Compared with the model group， high-dose Qiling prescription significantly reduced the serum levels of IL-1β， Caspase-3， PI3K， and Akt （P<0.01）， medium-dose significantly reduced the levels of IL-6， IL-1β， TNF-α， Caspase-3， PI3K， and Akt （P<0.05，P<0.01）. Compared to the blank group， the model group showed significantly increased expression of PI3K and Akt in gastric tissues. High-dose Qiling prescription significantly inhibited Akt protein expression compared to the model group （P<0.01）.Conclusion Qiling prescription may alleviate GIM and delay inflammation-cancer transformation through multi-component， multi-target， and multi-pathway mechanisms by inhibiting the PI3K/Akt pathway， reducing the release of pro-inflammatory factors， and inhibiting gastric mucosal epithelial cell apoptosis.

Abstract:The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

Abstract:As the foremost among the four examinations in traditional Chinese medicine （TCM）， inspection and related equipment research face challenges in landing and transformation due to variations in evidence quality， lack of standardization， insufficient algorithm transparency， and poor reliability and stability of decision-making. Against the backdrop of rapid development of emerging technologies such as big data， the internet of things， and artificial intelligence， coupled with macro policy support from the government， digital and intelligent generalized inspection in TCM has emerged， with the aim of utilizing digital technologies to overcome the limitations of naked-eye inspection and comprehensively perceive and analyze facial and bodily expressions. The research in this field intelligently correlates Zang-fu organ functions with health conditions and disease progression and establishes a technical system for digital and intelligent inspection， multi-dimensional and multimodal perception， fusion analysis， and decision-making. This system aims to enhance the accuracy of disease risk warning and diagnosis， bridging the gap between inspection equipment and assistance in clinical decision-making. From an evidence-based perspective， this paper systematically examines the research ideas of digital and intelligent inspection and the development of related equipment， deeply explores how to propose clinical practice-oriented key scientific issues， comprehensively acquire and co-apply multi-dimensional data， establish precise inspection models driven by digital intelligence， optimize standards to enhance equipment interoperability and reliability， construct post-effect evaluation mechanisms to promote improvement， and actively address potential risks such as the black box nature and information security in the application of intelligent technology. This paper not only demonstrates the tremendous potential of digital technologies in improving the accuracy and clinical application efficiency of inspection but also provides new perspectives and ideas for the modernization of inspection in TCM， paving the way for the application of inspection in the global medical and health field.

Abstract:The advent of digital times promotes the evolution of clinical research from traditional mode to digital mode. Digital technologies， which are introduced to clinical research of traditional Chinese medicine （TCM）， can optimize the research design， improve research quality， and save research funds and time. The digital and remote control of clinical research recruitment and screening， disease diagnosis and treatment， informed consent， indicator measurement， and other processes can be realized by computers， networks， sensors， and other technologies. Artificial intelligence （AI） algorithms， wearable monitoring devices， data management tools， blockchain， and virtual clinical trials （VCTs） are key innovation technologies and research design methods. On this basis， this study summarized relevant literature on key digital technologies and research methods such as AI algorithms， wearable monitoring devices， data management tools， blockchain， and VCT， and the following discoveries were obtained： The future development of clinical research of TCM requires to attach importance to the changes in clinical research brought by digital technologies and to promote the utilization of digital technologies in clinical research of TCM. Digital technologies realize the medical ethical ideas of ''putting people first''， promote the decentralization of clinical research， simplify the participation process of participants， reduce the time and cost of clinical research， improve the efficiency of clinical research of TCM， and enhance the objectivity， authenticity， and stability of clinical research of TCM. Deepening the application of digital technologies in clinical research and realizing the interaction and fusion of various digital technologies are inevitable trends of future development of clinical research of TCM. Under the background of digitization， the digital innovation of clinical research of TCM can accelerate the development of clinical research of TCM and promote the internationalization of TCM.

Abstract:In recent years， adaptive design has gradually emerged in clinical trials， gaining widespread application and expansion. Compared with traditional randomized controlled trials， appropriate adaptive design can save time and resources to some extent， improve the validity of the trial results and strength of the evidence， align better with ethical requirements， and facilitate subsequent drug market research. However， due to the greater flexibility of adaptive design， controlling type Ⅰ error rates and truly enhancing research efficiency are challenging aspects of its application. Therefore， the normative application and optimization of adaptive design in research deserve early focus， including adhering to good adaptive design principles， conducting rigorous pre-design planning， scientifically applying various statistical methods such as Bayesian dynamic models and simulation methods， and utilizing monitoring tools like monitoring committees to ensure the scientific integrity of the research process. Moreover， the flexibility of adaptive design aligns well with the practical realities of traditional Chinese medicine （TCM） clinical practice. The main characteristics of TCM， such as the holistic concept and treatment based on syndrome differentiation， determine that TCM provides a dynamic and personalized treatment plan. In contrast， the traditional fixed development approach of western medicine limits the application of "human experience" in TCM. To address this bottleneck in TCM research and development， the innovative use of adaptive design， a modern scientific theory and methodology with multiplicity and variability， offers a feasible new approach for TCM clinical research and the innovation of Chinese herbal medicine. By learning from successful cases such as the first Food and Drug Administration （FDA）-approved oral botanical drug， Crofelemer， researchers can explore optimal solutions for adaptive design in clinical research protocols and its role in the "three-combination" evaluation system for Chinese herbal medicines， further refine trial design， clarify key trial points， and develop innovative research and development applications that adapt to the clinical positioning of TCM and highlight the characteristics and advantages of TCM， paving the way for the clinical efficacy， pharmacological mechanism exploration， and post-market efficacy evaluation of Chinese herbal compounds.

Abstract:As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

Abstract:In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

Abstract:This study used the Appraisal of Guidelines Research & Evaluation-Health Systems （AGREE-HS） to demonstratively compare 34 global coronavirus disease-2019 （COVID-19） health systems guidance documents （HSGs） and 6 World Health Organization （WHO） standard HSGs. The comparison involved topic， participants， methods， recommendations， and implementability， with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%， with topic having the highest score， recommendations having the second highest score， and participants having the lowest score. The standard HSGs had an overall average score of 79%， with high scores in all items. The emergency HSGs had lower scores in participants， methods， recommendations， and implementability than the standard HSGs （P<0.001）， while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs （P<0.05）. Compared with those released by countries， the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores （P=0.000 2）. This indicates that emergency HSGs， represented by the COVID-19 emergency HSG， place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation， evidence support， and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics， clear purposes， orientation to demand， keeping up with the latest evidence， flexible adjustment， and timeliness， emphasizing immediate implementation effects， weakening long-term effects， and focusing on comprehensive benefits. Additionally， developers， types， and report completeness are important influencing factors.

Abstract:The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

Abstract:The formulation method of emergency health systems guidance （HSG） is crucial， directly impacting the efficiency and effectiveness of responses in emergencies. A scientifically sound， systematic， and easily executable guidance document can assist health institutions at all levels in quickly coordinating resources， standardizing emergency response processes， and safeguarding public health. This study employed the Appraisal of Guidelines for Research and Evaluation for Health Systems （AGREE-HS） to analyze the characteristics of participants in developing emergency HSGs represented by the COVID-19 emergency HSG. The results showed that in the 34 HSGs included in this study， the item participants received the lowest score. Within this item， criterion 1 （diversity of development group） scored the highest （3.13±1.55）， while criterion 5 （prevention of funding agency influence） scored the lowest （1.21±0.47）. There were differences （P<0.05） in measures taken to mitigate funding agency influence between the six standard HSGs developed by the World Health Organization （WHO） and the four emergency HSGs. Additionally， differences （P<0.05） existed in the development group members， background， conflicts of interest， and preventive measures between the six WHO standard HSGs and the 34 emergency HSGs， as well as between the HSGs developed by the WHO and those developed by countries. The participants in developing emergency HSGs were influenced by various factors， including limited time for guideline development， modes of participation， scarce evidence， and uncertainties in expected outcomes. There is a need to downplay extensive requirements concerning the composition of group members， institutional diversity， and conflicts of interest， emphasizing the roles of key participants like government officials and professionals who can provide rapid， practical guidance in emergency situations.

Abstract:Recommendations， consensus-based syntheses of the best available evidence， constitute the core content of a guideline. This paper analyzes the characteristics of emergency health systems guidance documents （HSGs）， represented by the coronavirus disease-2019 （COVID-19） emergency HSG， regarding the item "recommendations" and its eight evaluation criteria in the Appraisal of Guidelines for Research and Evaluation for Health Systems （AGREE-HS）. The World Health Organization （WHO） standard HSGs were used as reference to explore the characteristics of emergency HSGs that are different from non-emergency HSGs. The results showed that the “recommendations” scored second after “topic” among the five items. Criterion 7 relating to operability scored higher than others among the eight criteria， and criterion 3 dealing with ethical principles scored lower than other criteria. Compared with the standard HSGs， the emergency HSGs showed decreased scores （P<0.05） of the item recommendations and the criteria of this item except criterion 4 concerning equity promotion. Among the HSGs with different developers， those developed by the WHO had higher （P<0.05） scores of recommendations than nationally developed HSGs， as evidenced by criterion 4， criterion 5 involving acceptability to and alignment with sociocultural and political interests， and criterion 8 for updating plans. The HSGs regarding global or country strategy scored higher （P<0.05） on criterion 2 relating to comprehensiveness than those involving specific guidance on clinical or material issues. Overall， the emergency HSGs， represented by the COVID-19 emergency HSGs， differ from the standard HSGs in a number of ways in terms of their recommendations. Emergency HSGs have more condensed content and weaker articulation of expected outcomes. They incline to put more emphasis on updating plans， rather than comprehensiveness or integrative requirements in terms of ethics， equity， and sociocultural and political interests.

Abstract:The clear definition of the topic in emergency health systems guidance （HSG） ensures the relevance， scientific rigor， and practicality of the guidance， providing a clear direction and a framework for a rapid and effective public health response. This study used the Appraisal of Guidelines for Research & Evaluation-Health Systems （AGREE-HS） to demonstratively evaluate the global COVID-19 emergency HSGs and World Health Organization （WHO） standard HSGs， aiming to explore the characteristics of topic in emergency HSGs. The results showed that in the 34 HSGs included， the item topic received the highest score. Specifically， criterion 4 relating to relevant and applicable factors scored the highest （5.59）， while criterion 3 concerning the prioritization of health system challenges scored the lowest （2.76）. There were differences （P<0.05） in criterion 1 between standard HSGs and overall emergency HSGs， as well as between WHO and national emergency HSGs. Criterion 3 also showed differences （P<0.05） between standard HSGs and emergency HSGs， as well as between WHO and national emergency HSGs. Criterion 4 displayed differences （P<0.000 1） between WHO and national emergency HSGs. No differences were observed in intra-group or inter-group comparisons of different emergency HSG subcategories （P<0.05）. Overall， emergency HSGs represented by the COVID-19 emergency HSG focus on detailing the challenges faced by the health system， including the natures of challenges， affected populations， and other relevant and applicable factors， while aligning with stakeholder concerns. The prioritization is downplayed， with emphasis placed on rapid responses to and flexible handling of urgent issues. Influenced by factors such as the evidence base， phase timing， and effectiveness， the topic setting shows variations.

Abstract:Objective To establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine（TCM）. By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos， Houttuyniae Herba injection， Lonicerae Japonicae Flosand Buyang Huanwutang， this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship， namely half-life， statistical moment and statistics， in order to find the most suitable method for characterizing the relationship.Method Ten mice were randomly selected from 100 Kunming mice as the blank group， and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling， the mice were gavaged with aqueous extract of Lonicerae Flos（30 g?kg^-1）， and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time， the pharmacokinetic results of Houttuyniae Herba injection， Lonicerae Japonicae Flos and Buyang Huanwutang were included， and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method， statistical moment method and statistical method was compared.Result On the basis of the half-life method， the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied， with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity， the metabolic patterns among the components contained in Houttuyniae Herba injection， Lonicerae Japonicae Flos， Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method， statistical moment method and statistical method， and it was found that the difference between statistical moment method and half-life method was large， and the difference between statistical moment method and statistical method was small.Conclusion Statistical method not only reflects the characteristics of statistical moment method， characterizes the dispersion degree of each component， but also can be associated with fingerprint to form spectrokinetics， characterizing the dose-time relationship of 95% of drug components， which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

Abstract:Objective Ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS/MS） was used to investigate the metabolism and distribution of nardosinone in rats， then metabolic pathways were speculated.Method Rats were administered with 30 mg·kg^-1 of nardosinone suspension by gavage for 3 consecutive days， and plasma， urine， feces， and tissues of heart， liver， spleen， lung， kidney， brain， stomach， and intestine were collected at predetermined time points. After treatment， the samples were processed for UPLC-Q-Exactive Orbitrap MS/MS， and the MS data were analyzed using Xcalibur 2.2 software. The metabolites were searched by comparing the base peak chromatogram and extracted ion chromatogram between the treated group and blank group， and based on the relative retention time（t_R）， quasi-molecular ion peak， precise molecular mass， and fragment ions of MS/MS， the elemental composition were searched using databases such as SciFinder and PubChem， as well as referring to relevant literature， the possible metabolites were identified and the metabolic pathways were inferred.Result A total of 30 metabolites of nardosinone were identified， including 15， 19， 12， 7， 4， 11， 8， 13， 13， 8 and 12 metabolites in urine， feces， plasma， brain， heart， liver， spleen， lung， kidney， stomach and intestine， respectively. The main metabolic pathways of nardosinone in rats were hydroxylation， dehydroxylation， reduction， dehydrogenation， hydration， dehydration， carboxylation， glucuronidation， and dehydroxy-isopropyl.Conclusion Nardosinone can be metabolized by phase Ⅰ and phase Ⅱ metabolism in rats， and the metabolites are widely distributed in the major organs. The results of this study can provide a basis for further research on the pharmacodynamic material basis， pharmacological mechanism and clinical application of nardosinone.

Abstract:Objective Metabolomics was utilized to investigate the preventive effect of notoginseng total saponins（NTS） on aspirin（acetyl salicylic acid， ASA）-induced small bowel injury in rats.Method Fifty male SD rats were randomly divided into normal and model groups， NTS high-dose and low-dose groups（62.5， 31.25 mg·kg^-1）， and positive drug group（omeprazole 2.08 mg·kg^-1+rebamipide 31.25 mg·kg^-1）， with 10 rats in each group. Except for the normal group， rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg^-1 daily to establish a small intestine injury model. On this basis， each medication group was gavaged daily with the corresponding dose of drug， and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration， small intestinal tissues of each group were taken for hematoxylin-eosin（HE） staining， scanning electron microscopy to observe the damage， and the apparent damage of small intestine was scored. Serum from rats in the normal group， the model group， and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the data were processed by multivariate statistical analysis， the potential biomarkers were screened by variable importance in the projection（VIP） value≥1.0， fold change（FC）≥1.5 or ≤0.6 and t-test P<0.05， and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database（HMDB） and Kyoto Encyclopedia of Genes and Genomes（KEGG）.Result After 14 weeks of administration， the average body mass gain of the model group was lower than that of the normal group， and the NTS high-dose group was close to that of the normal group. Compared with the normal group， the fecal character score of rats in the model group was significantly increased（P<0.05）， and compared with the model group， the scores of the positive drug group and the NTS high-dose group were reduced， but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury， compared with the normal group， the small bowel injury score of the model group was significantly increased（P<0.01）， compared with the model group， the small bowel injury scores of the NTS low and high dose groups were significantly reduced（P<0.05， P<0.01）. Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group， of which 55 were up-regulated and 20 were down-regulated， 76 differential metabolites between the model group and the NTS groups， of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites（salicylic acid， 3-hydroxybenzoic acid and 4-hydroxybenzoic acid）， which were involved in 3 metabolic pathways， namely， the bile secretion， the biosynthesis of folic acid， and the biosynthesis of phenylalanine， tyrosine and tryptophan.Conclusion NTS can prevent ASA-induced small bowel injury， and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.

Abstract:Objective To explore the correlations between botanical characteristics， biological characteristics， growth environment， and medicinal properties of common pteridophyte-derived Chinese medicinal materials， thus providing evidence for the theory of quality evaluation through morphological identification and giving insights into the extensive and reasonable application of pteridophytes in traditional Chinese medicine （TCM）.Method The medicine parts， habitats， natures， tastes， and effects of the commonly used pteridophyte-derived Chinese medicinal materials were summarized. The commonly used pteridophyte-derived Chinese medicinal materials were retrieved from the Pharmacopoeia of China， Dictionary of Chinese Materia Medica， and related literature. Excel 2016， ChiPlot， Cytoscape 3.7.1， SPSS 21.0， and weiciyun software were used for statistical analysis.Result The frequency of the habitats followed the trend of streamside wetland>tree trunk and rock crevices>sunslope>water surface. The frequency of medicinal parts presented the trend of whole plant>rhizome>leaf>dried aboveground part>spore. The frequency of natures was in the order of cool>cold>plain>warm>hot， and that of tastes was in an order of bitter>pungent>sweet>bland>salty. The frequency of meridian tropism followed the trend of liver meridian>stomach meridian>lung meridian>kidney meridian>bladder meridian>heart meridian>large intestine meridian>spleen meridian>small intestine meridian. The effects of the pteridophyte-derived Chinese medicinal materials followed a frequency trend of clearing heat and detoxifying>promoting urination and relieving stranguria>cooling blood and stopping bleeding>activating blood and resolving stasis>dispelling wind and eliminating dampness.Conclusion The pteridophyte-derived Chinese medicinal materials mainly have a cool nature， a bitter taste， and tropism to the liver meridian. Whole plants and roots are mainly used for medicinal purposes， and most of these plants grow in the wetlands near rivers， under trees， and in tree trunk and rock crevices. The main effects of these medicinal materials are clearing heat and detoxifying， dispelling wind and removing dampness， cooling blood and stopping bleeding， activating blood and resolving stasis， and soothing meridians and dredging collaterals. There are certain correlations between the structures， habitats， medicinal parts， and effects of pteridophyte-derived Chinese medicinal materials， which provide reference for the development and utilization of pteridophyte-derived Chinese medicinal material resources.

Abstract:Objective To explore the correlations between the medicinal parts， habitats， tissue， components， and medicinal properties （natures， tastes， and effects） of 100 aquatic Chinese medicinal plants， thus providing evidence for the relationship between image and analogy and laying a theoretical foundation for the clinical use and development of aquatic Chinese medicinal plant resources.Method The Aquatic Plants of China， Flora of China， and related literature were searched， and a total of 100 aquatic Chinese medicinal plants included in the Chinese Pharmacopoeia （2020 edition）， Chinese Materia Medica， National Compilation of Chinese Herbal Medicines， Dictionary of Chinese Materia Medica， and local standards were screened out. The medicine-taxonomic status-life habit associations and nature-component-traditional Chinese medicine classification-pharmacological effect associations were analyzed respectively.Result The aquatic Chinese medicinal plants mostly had a cold nature， bitter， pungent， and sweet tastes， and tropism to the liver meridian. The whole plant or aerial part was mainly used for medicinal purposes， and these plants generally had well developed aerenchyma. These plants mainly contained flavonoids， alkaloids， and volatile oils and had the effects of clearing heat， detoxifying， and promoting urination.Conclusion There are correlations between the medicinal parts， habitats， tissue， components， medicinal properties， and effects of aquatic Chinese medicinal plants， which provide reference for the development and utilization of aquatic Chinese medicinal plant resources.

Abstract:Objective To make statistics on the biological characteristics， medicinal parts， chemical components， and other aspects of thorny medicinal plants and systematically analyze the correlations between their natures， tastes， and meridian tropism， so as to provide a theoretical basis for the clinical application and resource development of these plants.Method The Chinese Pharmacopoeia （2020 edition） and the processing standards of various provinces and cities and other related documents were reviewed， on the basis of which 46 species of thorny medicinal plants were selected. The natures， tastes， meridian tropism， medicinal parts， chemical components， pharmacological activities， and geographical distribution of these plants were summarized and analyzed in Excel 2013 and SPSS Statistics 26.0.Result The 46 species of thorny medicinal plants belonged to 25 families， 1 class， 1 phylum of 1 kingdom. In terms of the location of thorns， the frequency of these medicinal plants followed the trend of leaf thorns>peel thorns>branch thorns>fruit thorns. In terms of the nature， taste， and meridian tropism， the frequency of these plants was in the orders of warm>plain>cold>cool>hot， bitter>sweet>pungent>sour>salty， and liver>lung>spleen=large intestine>heart>kidney， respectively. In terms of the medicinal parts， the frequency followed the trend of roots and rhizomes>fruits>whole plants>flowers>leaves. The thorny medicinal plants were mainly distributed in north and southwest China. The thorny medicinal plants mainly contained flavonoids， alkaloids， and saponins and had the effects of clearing heat and detoxifying， resolving stasis and eliminating carbuncle， moving Qi and relieving pain， and alleviating edema and expelling pus. Moreover， 24 of them had anti-tumor activity.Conclusion Most of the thorny medicinal plants belong to Compositae， Leguminosae， and Rosaceae， have leaf thorns， a warm nature， a bitter taste， tropism to the liver meridian， and roots as the medicinal part. These plants are mainly distributed in north China， with the effects of clearing heat and detoxifying， resolving stasis and eliminating carbuncle. In summary， the thorn location， distribution， and medicinal parts of thorny medicinal plants are correlated with the natures， tastes， and meridian tropism. The findings provide clues for the development and utilization of these plants.

Abstract:Objective To compare the differences in intestinal absorption of nanophase（NP） formed by single decoction and combined decoction of Ginseng Radix et Rhizoma（GRR） and Zingiberis Rhizoma Recens（ZRR） in rats， and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR.Method Differential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR， respectively. The microstructure， particle size， Zeta potential and concentration of the NP were analyzed by transmission electron microscope， particle size analyzer and nanoparticle tracking analyzer. Based on everted gut sac model， the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）. The per unit area actual value of cumulative intestinal absorption（Q_actual）， absorption rate constant（K_a） and apparent permeability coefficient（P_app） were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum， jejunum， ileum and colon.Result Irregularly spherical NP was present in the single and combined decoctions， and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction. In these NP， ten components could be absorbed into the intestinal sac， with the main absorption site being the small intestine， and the P_app was greater than 1×10^-5 cm·min^-1. Compared with NP in the single decoction， the Q_actual and K_a of ginsenoside Rb₁， ginsenoside Rf， 4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction， while ginsenoside Re and 6-gingerol were significantly decreased（P<0.01）. Except for ginsenoside Re and ginsenoside Rd， the P_app of the remaining constituents was significantly increased in NP of the combined decoction（P<0.01）. In addition， the maximum intestinal segment site of Q_actual was shifted forward for ginsenoside Rb₁， ginsenoside Rd and ginsenoside Ro， while shifted backward for ginsenoside Rg₁， ginsenoside Re and 8-gingerol. The maximal intestinal segment sites of K_a and P_app of ginsenoside Rb₁， ginsenoside Rg₁， ginsenoside Rd and ginsenoside Ro shifted forward， while ginsenoside Re and 4-gingerol were shifted backward.Conclusion The combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two， and changes the absorption behavior of the effective components in some intestinal segments. This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.

Abstract:Objective A rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula.Method Based on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports.Result A total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively.Conclusion In this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Abstract:Glaucocalyxin A （GLA） is a natural diterpenoid extracted from Isodon amethystoides belonging to Labiatae. Modern pharmacological research has shown that GLA has anti-inflammatory， anti-tumor， anti-fibrotic， osteoporosis-ameliorating， and cardiovascular system-protecting activities and good biosafety. However， the low content in plants， poor solubility， high metabolic rate， and low bioavailability limit the application of GLA. To address these issues， researchers have studied the total synthesis， structural modification， and nanomedicine development of GLA. By reviewing the available studies about GLA in the past five years， we summarize the research progress in the total synthesis， pharmacological activities and mechanisms， and in vivo metabolic transformation， aiming to provide a theoretical basis for clarifying the specific mechanisms underlying the pharmacological activities of GLA and for further research， development， and clinical applications of GLA.

Abstract:Xihuang pills are a classic Chinese patent medicine following the theoretical principle of combining eliminating pathogen with reinforcing healthy qi in both local areas and the whole body， with the effects of clearing heat， detoxifying， alleviating edema， and dissipating mass. This medicine is traditionally used for treating carbuncle， furuncle， multiple abscess， carcinoma of breast， phlegm nodule， scrofula， lung abscess， and intestine abscess caused by fire depression， phlegm stasis， and heat toxin stagnation. It is used for treating malignant tumors， breast hyperplasia， herpes zoster， lymphadenitis， pelvic inflammatory disease， mastitis， vocal cord leukoplakia， and acne in modern medicine. Xihuang pills are now included in the 2020 edition of the Chinese Pharmacopoeia. The use of high-quality medicinal materials and modern technology enables full retaining of the active components in the medicinal materials. The chemical components in this medicine mainly include amino acids， terpenoids， fatty acids， fatty acid esters， phenols， bile acids， bile pigments， and volatile oils. Modern pharmacological studies have shown that a variety of active components such as bilirubin， bile acid， boswellic acid， and volatile oil in Xihuang pills interact with each other to exert anti-tumor， anti-breast hyperplasia， immunomodulatory， anti-inflammatory， and neuroendocrine-regulating effect. This paper reviews the research progress in the active components and pharmacological effects of Xihuang pills and predicts the quality markers （Q-markers） of this medicine according to the transmission， traceability， specificity， efficacy， measurability， and compound compatibility in the concept of Q-marker. It is suggested that bilirubin， bile acid， taurine， muskone， 11-carbonyl-β-boswellic acid， β-boswellic acid， 3-acetyl-11-keto-β-boswellic acid， octyl acetate， β-elemene， and myrrhone can be used as Q-markers of Xihuang pills， which can provide a basis for research on the material basis and the quality control of Xihuang pills.

Abstract:Amomi Fructus （AF） refers to the dried mature fruit of Amomum villosum A. villosum. var. xanthiondes， and A. longiligulare， all belonging to the Zingiberaceae family. As one of the renowned "Four Southern Medicines"， AF is also classified as an ingredient featured by "medicinal and food homology". It is mainly produced in Guangdong， Yunnan， and Hainan provinces in China. In recent years， with the in-depth implementation of the "Healthy China" strategy， AF has gained increasing popularity among the public due to its significant medicinal value. At the same time， research on its chemical composition， pharmacological effects， and identification methods has garnered widespread attention from scholars. The chemical composition of AF is highly complex. Its primary constituents include volatile components such as borneol acetate， camphor， and borneol， as well as non-volatile components such as polysaccharides， polyphenols， and mineral elements. AF possesses a wide range of pharmacological effects， including gastrointestinal protection， lipid-lowering and weight loss， glucose-lowering， uric acid-lowering， antioxidant， anti-inflammatory， antibacterial， and analgesic activities. The identification techniques for AF， including microscopic identification， molecular biological identification， and electrochemical fingerprinting， are crucial for its quality control， safety， and efficacy. However， in recent years， there have been few comprehensive summaries of research on AF， which limits further in-depth research and high-value development and utilization of AF. This article systematically reviewed the research progress on the chemical composition， pharmacological activity， and identification methods of AF， and is expected to provide prospects for future research.

Abstract:Colorectal cancer （CRC）， a most common malignant tumor of the digestive tract， is often manifested by abdominal pain， changes in stool quality， blood in the stool， and weight loss， with rising morbidity and mortality year by year. The onset and development of CRC involve a variety of mechanisms， in which tumor microenvironment （TME） and tumor-associated macrophages （TAMs） have received increasing attention. TAMs influence the tumor development via immune escape and angiogenesis promotion and are associated with the prognosis of tumors. In recent years， traditional Chinese medicine （TCM） has been widely researched and applied in the treatment of cancers. Studies have discovered that TCM mainly exerts the therapeutic effects on CRC by inhibiting the proliferation， metastasis， and angiogenesis， promoting the apoptosis， and inducing autophagy of tumor cells and boosting the immune function. TCM as an effective treatment approach can regulate TAMs to inhibit tumor growth. Moreover， the active components and targets of TCM can be taken as new research directions of immunotherapy. This review describes TAMs and their roles in CRC progression and summarizes the molecular targets and mechanisms of different active components， compound prescriptions， and novel preparations of TCM against CRC， aiming to provide a mechanism reference for the clinical treatment of CRC with TCM and give new insights into the in-depth research on the prevention and treatment of CRC-related diseases with TCM.

Abstract:Ankylosing spondylitis （AS） is an inflammatory autoimmune disease with chronic low back pain as the main clinical manifestation， which mainly affects the axial joints， peripheral joints and various organs. In severe cases， the spine is stiff or deformed， which affects the quality of life and health of patients. The pathogenic factors of AS are complex， which are related to heredity， immunity and intestinal flora. The pathogenesis of AS is not clear yet. Among them， inflammatory reaction， bone destruction and heterotopic ossification are the main pathological features of AS， which play an important role in the disease process of AS. Traditional Chinese medicine has multi-target， multi-channel and multi-component pharmacological effects， which can prevent and treat AS by anti-inflammation， inhibiting bone destruction and preventing heterotopic ossification， and the clinical effect is remarkable， but there is no relevant literature report. Therefore， this review expounds the relationship between inflammatory reaction， bone destruction and heterotopic ossification and the occurrence and development of AS， and summarizes the latest research reports of traditional Chinese medicine in treating AS from anti-inflammatory， inhibiting bone destruction and preventing heterotopic ossification， aiming at providing reference and new ideas and directions for further research on the prevention and treatment of AS by traditional Chinese medicine.