ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus（T2DM）poorly controlled with metformin. METHODS Based on the perspective of China’s health system， a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio（ICER） and incremental net monetary benefit （INMB） were calculated using one time the 2024 per capita gross domestic product（GDP） as the willingness-to-pay（WTP） threshold. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin， ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year （QALY），which was higher than the WTP threshold set in this study （95 749 yuan/QALY），and the corresponding INMB was －61 576.24 yuan，indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB，but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold，the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold，the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system， canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.

Objective:To analyze the epidemiological characteristics of the population receiving assisted reproductive technology (ART) therapy and the health status of their offspring in Shanghai from 2011 to 2020.Methods:Based on the birth cohort of the entire population in Shanghai, the proportion and trend changes of ART offspring in the birth cohort were analyzed. The characteristics of ART and naturally conceived populations, including household registration, education level, maternal age, and reproductive history, were examined. Additionally, the health status between ART offspring and naturally conceived offspring were compared.Results:From 2011 to 2020, a total of 70 729 ART offspring were born in Shanghai, accounting for 3.69% of the total births. In 2020, this proportion reached 7.79%. The ART conception rate for primiparous women was higher than that for multiparous women, with both showing upward trends and reaching 9.87% and 2.36%, respectively, in 2020. The ART conception rate was higher in women with higher education levels and local household registration than in those with lower education levels and non-local household registration. The incidence rates of preterm birth and low birth weight in ART singleton offspring were 7.76% and 4.82%, respectively, higher than the 4.69% and 2.87% in naturally conceived offspring, but no increasing trend was observed in naturally conceived offspring. Among twin and multiple newborns, the incidence rates of preterm birth and low birth weight were 56.98% and 46.82% for ART, lower than the 58.51% and 51.32% for natural conception.Conclusions:The difference in social and demographic characteristics was obvious in population receiving ART, suggesting that the differed demand of some people for ART therapy, and it is necessary to strengthen the construction of public health services and further expand the coverage and accessibility of ART services. With technological advancements, the rates of preterm birth and low birth weight remain relatively stable, and even decrease in twin and multiple newborns.

OBJECTIVE To evaluate the safety， efficacy， and cost-effectiveness of sodium-glucose co-transporter 2 （SGLT-2） inhibitors for treating type 2 diabetes mellitus （T2DM）. METHODS Retrieved databases such as PubMed， Cochrane Library， Embase， CNKI， as well as relevant health technology assessment （HTA） official websites， HTA reports， systematic review/meta- analysis and pharmacoeconomic studies about SGLT-2 inhibitors （including 12 types such as canagliflozin， dapagliflozin， and empagliflozin） in the treatment of T2DM were collected from the inception to January 28， 2025. After literature screening data extraction and quality assessment， a descriptive analysis was conducted on the results of the included studies. RESULTS A total of 38 articles were included， comprising 30 systematic reviews/meta-analyses， 4 pharmacoeconomic studies， and 4 HTA reports. In terms of effectiveness， most research results showed that canagliflozin was effective in controlling blood glucose， reducing body weight， and lowering blood pressure compared to other SGLT-2 inhibitors， while empagliflozin could effectively reduce all-cause mortality. In terms of safety， compared with other SGLT-2 inhibitors， empagliflozin has a lower overall adverse event rate and cardiovascular death risk， canagliflozin presented a higher risk of hypoglycemia， and dapagliflozin had a higher risk of urinary tract infections. In terms of economics， empagliflozin possessed greater economic advantages over both dapagliflozin and canagliflozin， while canagliflozin offered more benefits than dapagliflozin. CONCLUSIONS The selection of SGLT-2 inhibitors for the treatment of T2DM should be individualized. Canagliflozin is recommended for patients with high cardiovascular risk. Empagliflozin boasts the best overall safety profile. Dapagliflozin should be used with caution in patients at high risk of urinary tract infections. Based on foreign economic evidence， empagliflozin has economic advantages. In the future， drug economic studies under the Chinese health system need to be conducted.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

BACKGROUND:The imbalance between proliferation and apoptosis of chondrocytes plays an important role in the occurrence and development of osteoarthritis. Previous studies have found that hsa-miR-3202 is involved in regulating the proliferation and apoptosis of various cells. However,no studies have explored the correlation between hsa-miR-3202 and osteoarthritis.OBJECTIVE:To investigate the expression of hsa-miR-3202 in osteoarthritic chondrocytes and its effect on the proliferation and apoptosis of chondrocytes. METHODS:(1) MicroRNAs differentially expressed in osteoarthritic chondrocytes were screened by biogenic analysis. Based on the current research situation at home and abroad,hsa-miR-3202 was selected for follow-up studies,and its target genes were predicted by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. (2) Human normal chondrocyte cell lines C28/I2 in logarithmic growth phase were selected and randomly divided into four groups for culture:in normal group,cells were cultured in normal medium for 24 hours,the medium was then changed to normal medium for another 6 hours of culture,and changed to normal medium for subsequent culture;in lipopolysaccharide group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,the medium was then changed to normal medium for another 6 hours,and changed to normal medium for subsequent culture;in lipopolysaccharide+NC group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,and then transfected with has-miR-3202 mimics control for 6 hours,and the medium was change to normal medium for subsequent culture;in lipopolysaccharide+hsa-miR-3202 mimics group,cells were cultured in lipopolysaccharide-containing medium for 24 hours and then transfected with has-miR-3202 mimics for 6 hours,and the medium was changed to normal medium for subsequent culture. After further 48 hours of culture,the expression level of hsa-miR-3202 was detected by fluorescence quantitative PCR and cell apoptosis was detected by flow cytometry. After further culture of 0-72 hours,cell proliferation activity was detected by cell counting kit-8. RESULTS AND CONCLUSION:Bioinformatics analysis results indicated that hsa-miR-3202 was significantly down-regulated in osteoarthritic chondrocytes. GO functional enrichment and KEGG pathway enrichment showed that the function of hsa-miR-3202 target gene was closely related to cell growth and apoptosis. The results of in vitro cell experiments showed that compared with the normal group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly decreased in the lipopolysaccharide group (P<0.05),while the apoptotic rate was significantly increased (P<0.05). Compared with the lipopolysaccharide group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly increased in the lipopolysaccharide+hsa-miR-3202 mimics group (P<0.05),while the apoptotic rate was significantly decreased (P<0.05). To conclude,the expression of hsa-miR-3202 is down-regulated in osteoarthritic chondrocytes to inhibit cell proliferation and promote cell apoptosis,thus affecting the occurrence and development of osteoarthritis.

Objective To observe changes in voltage-dependent anion channel 3(VDAC3)in a mouse model of sepsis-induced myocardial injury and to explore its potential mechanism.Methods Twenty male C57BL/6J mice were divided randomly into a Sham group and Sepsis group,respectively(n=10 mice per group).Sepsis was induced by the cecal ligation and puncture(CLP).Serum levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,creatine kinase MB(CK-MB),and cardiac troponin T(cTnT)were detected by enzyme-linked immunosorbent assay.Pathological changes in heart tissue were observed by hematoxylin and eosin staining.Structural and functional changes in the heart were evaluated by echocardiography.Changes in total glutathione,reduced glutathione(GSH),oxidized glutathione,and malondialdehyde(MDA)in heart tissue were detected by spectrophotometry.The morphological structure of mitochondria in mouse cardiomyocytes was observed by transmission electron microscopy.Expression levels of IL-6,IL-1β,VDAC3,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),lipocalin-2(LCN2),and prostaglandin-endoperoxide synthase 2(PTGS2)mRNA were detected by real-time quantitative polymerase chain reaction and the localization and expression of VDAC3 and GPX4 proteins in mouse heart tissue were detected by immunofluorescence staining.The correlations between VDAC3 mRNA and GPX4,SLC7A11,PTGS2,LCN2,IL-6,and IL-1β mRNA were analyzed.Expression levels of VDAC3,GPX4,and SLC7A11 proteins were detected by Western blot.Results IL-6,TNF-α,CK-MB,and cTnT levels were significantly higher in the Sepsis group compared with the Sham group(P＜0.05).In the Sepsis group,myocardial fibers were torn,the ventricular wall was thickened and edematous,the mitochondrial membrane was ruptured,and mitochondrial cristae were broken or absent.GSH levels were significantly reduced in the Sepsis group(P＜0.05)and the lipid peroxide MDA was increased in the Sepsis group(P＜0.05)compared with the Sham group.VDAC3,GPX4 and SLC7A11 mRNA and protein levels were all lower in the Sepsis group compared with the Sham group(P＜0.05),while expression levels of IL-6,IL-1β,LCN2,and PTGS2 mRNA were increased(P＜0.05).VDAC3 mRNA was positively correlated with GPX4 and SLC7A11 mRNA levels,and negatively correlated with LCN2,PTGS2,IL-6,and IL-1β.Conclusions VDAC3 expression decreases in myocardial injury,and it may participate in the occurrence of sepsis-induced myocardial injury by regulating ferroptosis.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.