ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease.Early diagnosis is crucial for preventing disease progression and for effective treatment.Therefore,it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis. OBJECTIVE:Based on the Gene Expression Omnibus(GEO)database,to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology. METHODS:The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database.The data sets were merged using a batch effect removal method.Differential expression analysis and functional correlation analysis of genes were performed using R software.Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes,and key genes related to rheumatoid arthritis were screened.Furthermore,we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells. RESULTS AND CONCLUSION:In both rheumatoid arthritis and normal synovial tissues,we identified 179 differentially expressed genes,with 124 genes up-regulated and 55 genes down-regulated.Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response.Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis.LRRC15(area under the curve=0.964,95%confidence interval:0.924-0.992)and MICB(area under the curve=0.961,95%confidence interval:0.923-0.990)demonstrated strong diagnostic performance on the validation dataset.The infiltration of 13 types of immune cells was altered,with macrophages being the most affected.In rheumatoid arthritis,the majority of proinflammatory pathways in immune cell function were activated.Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages.To conclude,this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis,with strong diagnostic performance and significant correlation with immune cell infiltration.Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.

Staphylococcus aureus is a Gram-positive bacterium with strong pathogenicity. With the widespread use of antibiotics， its multi-drug resistance has gradually increased. Among them， methicillin-resistant S. aureus （MRSA） is one of the main pathogens of hospital and community infections. Antimicrobial peptides are short-chain peptides with good antibacterial effects and low drug resistance， which have been widely studied in recent years. This study summarizes the mechanism of action of antimicrobial peptides and related study on antimicrobial peptides against MRSA from different sources. It is found that the mechanisms of action of antimicrobial peptides include targeting bacterial cell membranes， bacterial cells， and bacterial cell walls， etc. Besides isolating antimicrobial peptides with anti-MRSA activity from animals， plants， and microorganisms， antimicrobial peptides can also be obtained through synthetic methods. Among them， GHa-derived peptides from animal sources， Ib-AMP4 from plant sources， Ph-SA from microbial sources， the synthetic peptide LLKLLLKLL-NH2， and so on， due to their effective antibacterial activity， rapid bactericidal speed， and low toxicity， are promising candidates for anti-MRSA drugs.

ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

Objective: o develop an onset risk prediction nomogram for patients with homocysteine-type (H-type) hypertension (HTH) based on pulse diagram parameters to assist early clinical prediction and diagnosis of HTH. Methods: Patients diagnosed with essential hypertension and admitted to Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai Hospital of Traditional Chinese Medicine, and Shanghai Hospital of Integrated Traditional Chinese and Western Medicine from July 6th 2020 to June 16th 2021, and from August 11th 2023 to January 22nd 2024, were enrolled in this retrospective research. The baselines and clinical biochemical indicators of patients were collected. The SMART-I TCM pulse instrument was applied to gather pulse diagram parameters. Multivariate logistic regression was adopted to analyze the risk factors for HTH. RStudio was employed to construct the nomogram model, receiver operating characteristic (ROC) curve, and calibration curve (bootstrap self-sampling 200 times), and clinical decision curve were drawn to evaluate the model’s discrimination and clinical effectiveness. Results: A total of 168 hospitalized patients with essential hypertension were selected and divided into non-HTH group (n = 29) and HTH group (n = 139). Compared with non-HTH group, HTH group had a lower body mass index (BMI), and higher proportions of male patients and drinkers (P < 0.05). The ventricular wall thickening (VWT) could not be determined. The proportions of left common carotid intima-media wall thickness (LCCIMWT) and serum creatinine (SCR) were higher in HTH group (P < 0.05). The pulse diagram parameter As was significantly higher, and H4/H1 and T1/T were lower in HTH group (P < 0.05). Gender, alcohol consumption, serum creatinine, and the pulse diagram parameter H4/H1 were identified as independent risk factors for HTH (P < 0.05). The nomogram’s area under the ROC curve (AUC) was 0.795 [95% confidence interval (CI): (0.706 6, 0.882 8)], with a specificity of 0.724 and sensitivity of 0.799. After 200 times repeated bootstrap self-samplings, the calibration curve showed that the simulated curve fits well with the actual curve (x2 = 9.5002, P = 0.301 9). The clinical decision curve indicated that the nomogram’s applicability was optimal when the threshold for predicting HTH was between 0.38 and 1.00. Conclusion The nomogram model could be valuable for predicting the onset risk of HTH and pulse diagram parameters can facilitate early screening and prevention of HTH.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.