Bruch's membrane opening(BMO)is the true anatomical border of the optic nerve head and provides higher anatomical accuracy, structural stability and measurement repeatability than traditional assessments based on the clinically visible optic disc margin. Optical coherence tomography(OCT)serves as a key technical tool for quantitative assessment of BMO-associated structural parameters. With the development of spectral-domain OCT(SD-OCT)and swept-source OCT(SS-OCT), parameters such as BMO-minimum rim width(BMO-MRW), BMO-minimum rim area(BMO-MRA), BMO area, offset, tilt, and torsion have emerged as important imaging biomarkers for evaluating optic nerve head morphology and for assisting in the diagnosis, staging, and longitudinal monitoring of glaucoma, myopia, and pathological myopia. Traditionally, the acquisition of these parameters has relied heavily on manual segmentation, which is limited by low efficiency, strong subjectivity, and considerable inter-observer variability. In recent years, artificial intelligence has been increasingly applied to OCT image segmentation, quality control, cross-device calibration, and automated quantitative analysis, thereby improving efficiency, objectivity, and reproducibility, particularly in eyes with complex optic disc morphology. This review summarizes recent advances in the BMO-related terminology standardization, imaging and quantitative methodologies, quality control,artificial intelligence-assisted analysis, as well as clinical evidence of its application in glaucoma, myopia and pathological myopia. Particular emphasis is placed on their potential value in the differential diagnosis and follow-up evaluation of highly myopic eyes with glaucoma, aiming to provide a reference for the standardized clinical application and future translational use of BMO-related parameters.

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained 10.24%,with a significant difference between the two groups(P<0.05).The weight of mice in CID+FMT group decreased by 8.12%,which was significantly improved compared to CID model group(P<0.05).HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged,with atrophy and deformation,accompanied by inflammatory cell infiltration,and the pathological score was higher than that of control group(P<0.05).Compared with CID model group,the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved,with less damage,and the pathological score was lower than that of CID model group,but the difference was not statistically significant(P>0.05).The α-diversity analysis showed that there were significant differences in the Shannon,Simpson and Chao1 indices among the three groups(P<0.05).ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group.LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae,and the intestinal flora in CID+FMT group was similar to that of control group,with an enrichenment of familiy_Enterobacteriaceae.Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice,making it more similar to normal intestinal flora,thereby protecting intestinal mucosa,reducing damage and alleviating the severity of CID.

Non-functioning pituitary adenomas(NFPAs)are relatively common.Apart from hyperprolactinemia caused by pituitary compression,they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects.Previously considered a uniform entity,NFPAs are actually a highly heterogeneous group of tumors,including aggressive subtypes like silent corticotroph adenomas(SCA)and null cell adenomas.The 2022 WHO new classification of pituitary tumors employs transcription factors[e.g.,pituitary-specific transcription factor 1(PIT-1),T-box transcription factor 19(TBX19,also known as TPIT),steroidogenic factor 1(SF-1)]for detailed categorization,allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages,including silent gonadotroph adenomas,SCA,and plurihormonal PIT-1-positive adenomas.This helps identify highly invasive subtypes with high recurrence risk,guiding clinical diagnosis and treatment,prognostic assessment,and individualized management.The new classification also provides a theoretical basis for targeted therapies of NFPAs(e.g.,somatostatin analogs and temozolomide).This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications,aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis,treatment,and prognostic assessment.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.