BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective To explore the feasibility and accuracy of neutrophil-to-lymphocyte ratio(NLR)in the prediction of testicular torsion(TT)in children with acute scrotal pain.Methods A retrospective case-control study was performed on 158 pediatric patients with ultrasound suspicion of TT who underwent surgical testicular examination during Jan.2017 and Jan.2024.The patients were divided into TT group and non-TT group.Clinical data and laboratory data at admission were analyzed.Sensitivity and specificity of NLR to TT were determined with the area under the curve(AUC)represented on the receiver operating characteristic(ROC)curves.Results There were with no statistically significant differences in clinical data between the two groups(P＞0.05).The NLR was significantly higher in the TT group than in the non-TT group[(4.82±2.37)vs.(2.85±0.75),P＜0.05].The optimal cut-off value of TT predicted by NLR was 2.07,the AUC was 0.809(95％CI:0.709-0.909),and the sensitivity and specificity were 97.9％and 93.3％,respectively,which were significantly higher than other factors.Conclusion For suspicious ultrasound diagnosis of pediatric acute scrotal pain cases,NLR can be used to predict the possibility of TT and may help to evaluate the urgent surgical treatment in these patients.

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Objective:To investigate the effect and mechanism of vitamin D supplementation on Hashimoto′s thyroiditis(HT).Methods:Female SD rats were randomly divided into four groups by random number table method: control group, experimental autoimmune thyroiditis(EAT) control model group(model group), low-dose(VD1 group) and high-dose(VD2 group) active vitamin D intervention groups. The morphology of thyroid cells, thyroid function, thyroid antibodies, various CD4 + T cells, and related cytokine levels among different groups were compared. Results:The levels of thyroid peroxidase antibody(TPOAb) and thyroid globulin antibody(TgAb) in model group were significantly higher than those in control group, while the levels of VD1 and VD2 groups were significantly lower than those in model group( P<0.05). Compared with control group, HE staining in model group showed severe damage of follicular epithelial cells; Compared with model group, the degree of atrophy and destruction of follicular epithelial cells in VD1 and VD2 groups were reduced. The proportion of helper T cell(Th)1 and Th17 cells and related cytokine levels in model group were significantly higher than those in control group, while those in VD1 and VD2 groups were lower than those in model group( P<0.05); The proportion of regulatory T cell(Treg) cells and related cytokine levels in model group were significantly lower than those in control group, while those in VD1 and VD2 groups were higher than those in model group( P<0.05). Conclusions:After supplementing with vitamin D, the levels of TPOAb and TgAb in EAT rats decreased, and the number of various CD4 + T cells and related cytokine levels tended towards normalization. This suggests that vitamin D may improve HT by regulating CD4 + T cell differentiation, providing a theoretical basis for the role of vitamin D supplementation in HT treatment.

Objective:To investigate the early and mid-term outcomes of aortic endovascular remodeling device (AERD) for Stanford type A aortic dissection (TAAD) in type Ⅱhybrid surgery, and to evaluate its clinical efficacy.Methods:46 patients with TAAD, including 14 females and 32 males, participated in the single-center clinical trial of West China Hospital of Sichuan University and underwent type II hybrid surgery (Bentall / ascending aorta replacement + AERD implantation) from February 2021 to October 2023. The safety and efficacy of AERD in type Ⅱ hybrid surgery for TAAD were estimated by clinical indicators (postoperative mortality, cardiovascular and cerebrovascular accidents, paraplegia, ischemia), and blood flow condition (volume of the true and false lumen, and suprachial branches).Results:Three patients (6.52%) died during the follow-up period, and the operation-related mortality was 4.35% (2/46). The remaining 43 patients were followed up for an average of (25.53±9.60) months. There were two cases (4.35%) of stroke after the operation, and paraplegia, acute renal insufficiency, and other severe complications were not noticed. The blood flow of the superior branch of the aortic arch was unobstructed, and there was no significant difference in the blood flow of the branch before the operation and at each follow-up time point. Compared to the pre-operation, the true lumen volume of the stent part increased by 59.0% and the false lumen volume decreased by 82.4%.Conclusion:AERD is a safe and effective alternative in type II hybrid surgery for acute TAAD, which is helpful in improving perioperative and short- and long-term survival rates and clinical outcomes.

Objective:To investigate the correlation of atrophy and intestinal metaplasia (IM) stage with gastric cancer and to optimize biopsy strategy.Methods:Data of patients who underwent endoscopy and five-point biopsy at Shandong Provincial Hospital between November 2020 and October 2022 were collected. The baseline characteristics of gastric cancer and non-gastric cancer patients, as well as the occurrence and severity of atrophy and IM in different areas were compared. Logistic regression analysis was used to evaluate the correlation of operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging with gastric cancer. The Kendall tau correlation coefficient was used to compare the consistency of different biopsy strategies (two-point, three-point, and four-point) with the standard five-point biopsy in OLGA and OLGIM staging. Receiver operating characteristic (ROC) curve analysis was further performed to compare the diagnostic performance of different biopsy strategies in identifying the OLGA and OLGIM Ⅲ-Ⅳ stage.Results:A total of 122 patients were included in the analysis, with age of 61.0±10.0 years. Multivariate analysis showed that OLGA staging was not associated with gastric cancer ( P=0.788), while OLGIM Ⅲ-Ⅳ staging was significantly correlated with gastric cancer ( P=0.006, OR=3.39, 95% CI: 1.41-8.17). The occurrence of atrophy and IM were higher in lesser curvature of the antrum [56.6% (69/122) and 66.4% (81/122)] and incisura angularis [57.4% (70/122) and 52.5% (64/122)], with higher severity, while lower in greater curvature of the corpus [2.5% (3/122) and 5.7% (7/122)], with lower severity. The consistency of four-point and three-point biopsies with standard five-point biopsy in OLGA and OLGIM staging was high. The consistency of three-point biopsy in incisura angularis, lesser curvature of the antrum and corpus was exceptionally high among them, with correlation coefficients of 0.969 and 0.987, respectively. Conclusion:OLGIM Ⅲ-Ⅳ stages increase the risk of gastric cancer. Three-point biopsy in incisura angularis, lesser curvature of the antrum and corpus are recommended for the screening and monitoring of atrophy or IM.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explore the regulatory effects and mechanism of melatonin on the proliferation and osteogenic differentiation of human dental pulp stem cells(hDPSCs).Methods:hDPSCs were cultured in vitro.The cells in the blank control groups were rou-tinely cultured,while the cells in the experimental groups were cultured with osteogenic induction medium(OIM)and OIM with me-latonin at 5,1,10,25,50,100,500 and 1 000 μmol/L respectively.The effect of melatonin on the proliferation of hDPSCs was ob-served by CCK-8 assay.Alkaline phosphatase(ALP)test,RT-qPCR and Western blot were used to analyze the expression of osteo-genic related genes and proteins.The expression level of the proteins related to classical Wnt pathway was detected.Results:Melato-nin at 100 and 250 μmol/L promoted the proliferation of hDPSCs,at 100 μmol/L increased the expression levels of osteogenesis-related mRNA and proteins in hDPSCs,up-regulated β-catenin and down-regulated GSK-3β expression.Conclusion:Melatonin at specific concentrations can promote the proliferation of hDPSCs and has the potential to regulate Wnt/β-catenin signal pathway to pro-mote osteogenic differentiation of hDPSCs.