Objective To analyze the clinical value of plasma insulin-like factor 6(INSL6)in predicting the risk of acute aortic syndromes(AAS)and adverse outcomes.Methods A retrospective case-control trial was conducted on 194 AAS patients admitted to Department of Cardiovascular Diseases of Second Affiliated Hospital of Army Medical University between April 2021 and June 2023.Another 194 sex-,age-and BMI-matched individuals without aortic diseases were recruited from the health examination center between December 2021 and January 2024.Their plasma INSL6 level was measured with ELISA,and the general clinical data and results of some laboratory tests were collected and compared between the 2 groups.Spearman correlation analysis was used to assess the relationship between plasma INSL6 and other variables,receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of INSL6 for AAS occurrence,multivariate conditional logistic regression model was utilized to analyze the association between plasma INSL6 and AAS onset,and Kaplan-Meier survival curve and multivariate Cox proportional hazards regression model was applied to analyze the relationship between acute-phase plasma INSL6 level and adverse prognosis in AAS patients.Results The plasma INSL6 level was significantly higher in AAS patients at acute phase than the control individuals[704.40(481.32～1 152.62)vs 141.24(107.60～163.72)pg/mL,P<0.001],but no statistical difference was observed in the level among the patients with different AAS subtypes(aortic dissection,intramural hematoma,and penetrating aortic ulcer).Spearman correlation analysis showed that the plasma INSL6 level was positively correlated with platelet count(r=0.325,P<0.001)and hemoglobin concentration(r=0.186,P=0.009),and negatively with IL-6(r=-0.182,P=0.011),INF-γ(r=-0.283,P<0.001),and D-dimer levels(r=-0.195,P=0.006).Multivariate conditional logistic regression analysis revealed that plasma INSL6 level was independently associated with the occurrence of AAS(OR=28.634,95%CI:7.267～112.820,P<0.001).ROC curve analysis further confirmed that the optimal cutoff value of plasma INSL6 in predicting AAS was 259.425 pg/mL,with a sensitivity of 95.9%and a specificity of 98.5%at this threshold.Kaplan-Meier curve analysis demonstrated that AAS patients with low INSL6 level had significantly lower cumulative survival rates(P=0.020)and event-free survival rates(P=0.004)than those with high INSL6 level(P<0.05).Multivariate COX regression analysis revealed that,after adjusting for sex,age,systolic blood pressure,ST classification,and surgical treatment,acute-phase INSL6 level was independently associated with all-cause mortality(HR:0.999,95%CI:0.999～1.000,P=0.023),AAS-related mortality(HR:0.999,95%CI:0.998～1.000,P=0.012),and composite endpoint events(HR:0.999,95%CI:0.999～1.000,P=0.026)in AAS patients during follow-up.Conclusion Plasma INSL6 level is closely associated with the occurrence and adverse prognosis of AAS,and the indicator is expected to be an effective biomarker for diagnosing AAS and predicting its prognosis.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Objective:To explore if miR-133a is involved in the occurrence and development of hepatocellular carcinoma(HCC)via regulating G6PD.Methods:Bioinformatics analysis predicted the binding sites of miR-133a and G6PD;RT-PCR or western blot was used to assess the expres-sion of miR-133a and G6PD in HCC tissues and the adjacent normal tissues;CCK-8 and flow cy-tometry assays were performed to evaluate the effects of miR-133a/G6PD on cell proliferation,apop-tosis;Fluorescent reporter gene and western blot assays were used to assess the effect of miR-133a on G6PD expression.Results:miR-133a expression was decreased in HCC tissues while G6PD was increased(P0.01);Up-regulation of miR-133a significantly reduced G6PD expression(P＜0.01);up-reg-ulation of miR-133a inhibited cell growth and promoted cell apoptosis(P＜0.05),whereas these effects induced by miR-133a over-expression were all abolished when G6PD was up-regulated(P＜0.01).Conclusion:miR-133a represses the occurrence and development of HCC via targeting G6PD.

Background: Aortic valve sclerosis (AVS) shares risk factors with atherosclerosis. However, the relationship between AVS progression with cardiovascular (CV) risk has not been researched. This study investigates CV outcomes according to progression of AVS. Methods: This study included 2,901 patients with AVS (irregular leaflet thickening and peak aortic jet veloc‑ ity < 2 m/sec) who underwent serial echocardiograms at least 1 year apart during 2011–2020. The primary outcome was defined as CV death, myocardial infarction, stroke, or revascularization. Results: During a median follow-up period of 3.9 years, 439 of 2,901 AVS patients (15.1%) progressed to mild or greater aortic stenosis. Patients with progression were older and more likely to have atrial fibrillation than those without. In a stepwise regression, age (odds ratio [OR] per 1-year increase, 1.04; 95% confidence interval [CI], 1.01– 1.07), peripheral artery disease (OR, 9.07; 95% CI, 3.12–26.4), and left ventricular mass index (OR per 1-g/m 2 increase, 1.01; 95% CI, 1.00–1.02) were associated with AVS progression. Over a median of 6.3 years, the primary outcome occurred in 858 of 2,901 patients (29.6%). Patients with progression had higher frequency of CV death, myocardial infarction, stroke, or revascularization than those without progression (P < 0.0001). In Cox proportional hazards regres‑ sion, AVS progression (hazard ratio, 1.33; 95% CI, 1.10–1.61) was a significant determinant of CV mortality. Conclusions The progression to aortic stenosis in AVS patients is an independent risk factor for CV mortality. These findings suggest that patients with AVS progression may benefit from stricter CV risk monitoring.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs.2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49％,101.88％and 101.89％,respectively,with 90％confidence intervals of 98.18％-111.20％,97.80％-106.13％and 97.87％-106.07％,all within the range of 80.00％-125.00％.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34％,103.55％and 102.98％,respectively with 90％confidence intervals of 101.69％-113.31％,99.94％-107.30％and 99.65％-106.43％,all within the range of 80.00％-125.00％.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.