ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

ObjectiveTo introduce visual teaching into the course design of medical humanistic care based on the concept of implementation science， evaluate the teaching implementation effect and feedback， and provide references for optimizing course teaching outcomes and improving students’ humanistic care competence. MethodsA visual teaching program for medical humanistic care was designed， with key steps including clarifying teaching objectives， content， methods， and curriculum assessment. This program was implemented in the medical humanistic care course teaching involving 50 elective students. Multi-dimensional evaluation of teaching effectiveness was conducted through course grades， visual teaching evaluation， and humanistic workshop assessment， combined with inductive content analysis of students’ learning experiences in the workshops. ResultsThe 50 students achieved above-average course grades （89.60±3.41） and demonstrated high satisfaction with the overall course and visual teaching. All the 6 groups obtained relatively high scores in the medical humanistic care workshops. Four themes were extracted， namely， enhancing humanistic care competencies， deepening familial and interpersonal relationships， realizing emotional expression and self-growth， and strengthening integration of humanistic care concepts with practice. ConclusionThe teaching of medical humanistic care course has achieved favorable effects， which contributes to deepening students’ understanding of humanistic care and enhancing their humanistic care competence. Students demonstrate high levels of recognition and satisfaction with the course.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To investigate the effect of the embryo cryopreservation duration on pregnancy and obstetric outcome.Methods:A retrospective cohort study of 2 662 frozen-thawed embyro tranfer (FET) cycles was conducted in the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital from January 2016 to December 2020. According to embryo cryopreservation duration, the patients were divided into group A (≤1 year, n=2 115), group B (>1 years and ≤3 years, n=319), group C (>3 years and ≤6 years, n=174), and group D (>6 years, n=54). We used the propensity score matching (PSM) to match the baseline data of oocyte retrieval age of the other three groups according to group D at a ratio of 1∶3. Clinical and obstetric outcomes were compared among the four groups. Multiple logistic regression analysis was used to analyze the effect of oocyte retrieval age, embryo transfer age, the duration of embryo cryopreservation, endometrial preparation scheme, endometrial thickness, the number of transferred embryos and the number of high-quality embryos on pregnancy and live birth outcome. Results:1) Before PSM, there were significant differences in the maternal age at oocyte retrieval and embryo transfer and duration of embryo cryopreservation among the four groups(all P<0.001). 2) After PSM, the baseline characteristics of oocyte retrieval age reached a balance among the four groups. There were no statistical differences in the number of embryos transfer, the number of high-quality embryos, the transferred embryo stage, the endometrial regimen among the groups (all P>0.05). The clinical pregnancy rate [37.04% (20/54)] and the live birth rate [33.33% (18/54)] in group D were lower than those in group A [51.57% (82/159), 40.88% (65/159)], group B [50.00% (65/130), 40.77% (53/130)] and group C [49.59% (61/123), 39.02% (48/123)], but the difference was not statistically significant between the four groups ( P=0.310, P=0.781). There were no statistical differences among the four groups in the ratio of male to female newborns, gestational age, birth weight, preterm delivery rate, low birth weight rate, macrosomia rate, birth defects, and premature repture of membranes (all P>0.05). 3) Multiple logistic regression analysis showed that the number of high-quality embryos transferred affected the clinical pregnancy outcome (before PSM, OR=2.614, 95% CI: 2.168-3.151, P<0.001; after PSM, OR=1.984, 95% CI: 1.406-2.800, P<0.001) and live birth (before PSM, OR=2.708, 95% CI: 2.198-3.336, P<0.001; after PSM, OR=2.122, 95% CI: 1.474-3.053, P<0.001). The duration of embryo cryopreservation does not affect the clinical outcome and live birth (all P>0.05). Conclusion:The duration of embryo cryopreservation does not affect the clinical outcome and live birth, but large sample data are still needed to support this conclusion in the future.

Background and Aims:Long noncoding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)is an oncogenic lncRNA that promotes the progression of various cancers through the competing endogenous RNA(ceRNA)mechanism.Using the TargetScan database,we previously identified binding sites between NEAT1 and microRNA-124-3p(miR-124-3p),as well as between miR-124-3p and catenin beta-1(CTNNB1).Therefore,this study was conducted to investigate the expression of NEAT1,miR-124-3p,and CTNNB1 in pancreatic cancer and their interactions affecting pancreatic cancer cell functions.Methods:A dual-luciferase reporter assay was used to validate the relationships among NEAT1,miR-124-3p,and CTNNB1.The expression levels of NEAT1 and miR-124-3p,as well as CTNNB1 protein expression,were detected in pancreatic cancer tissues and adjacent normal tissues,as well as in pancreatic cancer PANC-1 cells and normal pancreatic epithelial H6C7 cells.PANC-1 cells were transfected with NEAT1 siRNA alone or co-transfected with a miR-124-3p inhibitor.After transfection,changes in PANC-1 cell biological functions,epithelial-mesenchymal transition related protein expression,and tumor growth ability in mice were assessed.Results:The dual-luciferase reporter assay confirmed the targeting relationships between NEAT1 and miR-124-3p,as well as between miR-124-3p and CTNNB1.NEAT1 and CTNNB1 expression levels were significantly upregulated,while miR-124-3p expression was downregulated in pancreatic cancer tissues(vs.adjacent tissues)and in PANC-1 cells(vs.H6C7 cells)(all P<0.05).NEAT1 siRNA transfection led to decreased NEAT1 and CTNNB1 expression and increased miR-124-3p expression in PANC-1 cells.However,co-transfection with a miR-124-3p inhibitor suppressed the expression changes in miR-124-3p and CTNNB1(all P<0.05).NEAT1 siRNA transfection significantly reduced PANC-1 cell proliferation,migration,and invasion,while promoting apoptosis.Additionally,E-cadherin protein expression was upregulated,whereas N-cadherin and vimentin protein expression were downregulated.Tumor growth in mice was also significantly inhibited(all P<0.05).These changes were attenuated upon co-transfection with the miR-124-3p inhibitor(all P<0.05).Conclusion:NEAT1 may act as a ceRNA by competitively binding to miR-124-3p,thereby attenuating miR-124-3p-mediated inhibition of CTNNB1.This leads to CTNNB1 upregulation,ultimately promoting the malignant biological behavior of pancreatic cancer cells.