ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

Myocardial infarction （MI） refers to an acute clinical syndrome of myocardial necrosis due to persistent ischemia and hypoxia， resulting from the sharp reduction or interruption of coronary blood flow. Nuclear factor κB （NF-κB） is the key factor in inducing inflammatory response， and it is involved in the production of pro-inflammatory factors and myocardial cell apoptosis. This article systematically describes the molecular regulation mechanism of the NF-κB signaling pathway in MI， and reviews the related research on the prevention and treatment of MI through the regulation of this signaling pathway by active ingredients and compound formulas from traditional Chinese medicine （TCM）. It has been found that active ingredients from TCM， such as ginsenoside Rg3， baicalein， curcumin， tanshinone ⅡA， gambogic acid， as well as compound formulas， including Qili qiangxin capsules， Yiqi huoxue decoction， Lingbao huxin dan， Danhong injection， Baoyuan decoction combined with Taohong siwu decoction， can improve myocardial fibrosis， alleviate inflammatory responses， and inhibit cardiomyocyte apoptosis by suppressing the NF-κB signaling pathway. Thereby， they achieve the goal of preventing and treating MI.

Myocardial ischemia-reperfusion injury （MIRI） is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress， iron overload， inflammatory responses， and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions， characterized by the abnormal accumulation of reactive oxygen species （ROS）， which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 （Nrf2）， adenosine monophosphate-activated protein kinase （AMPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor kappa-B （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species （PKCβⅡ/NOX2/ROS）. This article reviews recent literature on TCM monomers， compound formulas， and their active components， which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI， discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI， and explores clinical application prospects and research challenges， aiming to provide a theoretical reference for the research and clinical management of MIRI.

Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.

Preterm birth is the most common maternal complication in twin pregnancies. In recent years, cervical cerclage has been of long-standing interest in the prevention of preterm birth in twin pregnancies. However, its clinical application in the treatment of cervical insufficiency of twin pregnancies remains a controversial subject. In addition, infection or inflammation conditions are considered to be closely related to the perinatal outcomes of twin pregnancies after cervical cerclage. This paper reviews the research progress on cervical cerclage in twin pregnancies, recommending cervical cerclage for twin pregnancies with cervical length≤15 mm or cervical dilatation, while it is not suggested for those with cervical length of 15-25 mm or history-indicated cervical cerclage. The clinical significance of preoperative evaluation of intraamniotic infection or inflammation of twin pregnancies needs to be further explored, but it is necessary to avoid the effect of antibiotic use on the evaluation of surgical effects.

Objective To explore the effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NOD-like receptor protein 3(NLRP3)inflammasome in patients with irritable bowel syndrome(IBS).Methods A total of 120 patients with IBS admitted to the hospital were prospectively enrolled as the research objects between January 1,2021 and December 31,2022,and they were randomly divided into control group(60 cases)and treatment group(60 cases).The control group was treated with compound eosinophil-Lactobacillus,while treatment group was additionally treated with simethicone.The curative effect after treatment,scores of gastrointestinal symptom rating scale(GSRS),levels of somatostatin(SS),vasoactive intestinal peptide(VIP),NLRP3 inflammasome,interleukin-8(IL-8)and interleukin-1β(IL-1β),counts of intestinal floras before and after treatment,and safety during treatment were compared between the two groups.Results After treatment,total response rate of treatment group was higher than that of control group(91.67% vs.76.67% ,P<0.05).After treatment,GSRS scores in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,levels of SS and VIP in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,counts of eosinophil-Lactobacillus and Bifidobacteria were increased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference in counts of intestinal floras between the two groups(P>0.05).After treatment,levels of NLRP3 inflammasome,IL-8 and IL-1β were decreased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference between the two groups(P>0.05).During treatment,there was no significant difference in side effects between the two groups(P>0.05).Conclusion Simethicone can significantly improve response rate of treatment,improve gastrointestinal symptoms and gastrointestinal hormones in IBS patients,which has no significant effects on intestinal floras and inflammatory process mediated by NLRP3 inflammasome,with good safety.

Objective: To evaluate the bidirectional association between periodontitis and Sjögren's syndrome using the Mendelian randomization (MR) method. Methods: Genome-wide association study (GWAS) data of periodontitis (N = 45 563) and Sjögren's syndrome (N = 214 435) were selected to meet the requirements of the same ethnicity and different regions. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) tests were used to evaluate the causal effect. Cochran's Q statistics, MR-Egger intercept, MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results. Results: After screening, the GWAS data of Sjögren's syndrome were based on the Finnish region, and the periodontitis GWAS data were based on the UK region, both of which originated from European ancestry. Using IVW (OR = 1.017, 95% CI = 0.956-1.082), MR-Egger (OR = 0.985, 95% CI= 0.956-1.082), and WM (OR =1.021, 95% CI = 0.948-1.099), no causal effect of Sjögren's syndrome on periodontitis was found using any of the three methods. Conversely, no causal effect of periodontitis on Sjögren's syndrome was found (IVW, OR = 1.024, 95% CI = 0.852-1.230; MR-Egger, OR = 0.978, 95% CI = 0.789-1.212; WM, OR = 1.024, 95% CI = 0.846-1.260). The sensitivity analyses indicated that the results were stable and reliable. Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables, which included single nucleotide polymorphisms (SNPs). The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs. No individual SNP was found that significantly affected the results using the leave-one-out method. Conclusion This study does not support a bidirectional causal effect between periodontitis and Sjögren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.