OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective This study aims to establish a hidden curriculum-based medical humanities teaching pathway within surgical internship education and evaluate its effectiveness in enhancing students' humanistic care competence.Methods A single-group pre-test and post-test design was adopted.A total of 76 interns from a tertiary teaching hospital in 2024 were in-cluded.A five-dimensional hidden curriculum framework—material,spiritual,behavioral,faculty,and institutional—was con-structed.Humanistic competence was assessed before and after the intervention using the Humanistic Professional Awareness Scale for Healthcare Students and Providers(HPAS-HSP).Results Post-intervention scores significantly improved compared to pre-intervention across the total scale in the three dimensions:personal integrity and responsibility,sensitivity to others,and pro-fessional competence(P＜0.05),with the greatest improvement observed in sensitivity to others.Conclusion The structured hidden curriculum is effective in enhancing medical students' humanistic qualities,especially in fostering emotional resonance and professional identity.Future work should focus on verifying behavioral transformation and developing multi-source evaluation sys-tems to improve effectiveness and applicability.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.

Objective:To evaluate the effectiveness of entrustable professional activities (EPAs) in the general practice internship of undergraduate clinical medicine students, identify issues that need improvement in the internship, and enhance medical students' competence.Methods:A total of 75 students in the five-year (English class) clinical medicine program enrolled in 2018 and 2019 who participated in general practice internship in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2021 to October 2023 were selected as study subjects. The design of core EPAs was adopted to assess the correlation among different EPA dimensions and to analyze the qualified rates.Results:The evaluation of EPAs showed that EPA2 (practicing respect, understanding and teamwork) had the highest mean score of 9.33, and EPA10 (chronic disease management and management of key populations) had the lowest mean score of 8.08. A supervision level of 3a and above was used as the criterion for qualification. The supervision levels of the students' EPAs were mostly concentrated at levels 3a and 3b. The highest qualified rate was for EPA2 (practicing respect, understanding and teamwork) at 85.33%, followed by EPA1 (complying with the rules of the profession and demonstrating professionalism) at 80.00% and EPA8 (reviewing information and solving clinical problems) at 72.00%. The lowest qualified rate was for EPA10 (chronic disease management and management of key populations) at 33.33%, followed by EPA4 (analyzing and interpreting test results) at 57.33%.Conclusions:EPAs concretize competency evaluation, which can effectively reflect the "competency-oriented" training objectives encompassing multiple elements such as knowledge, skills, values, and attitudes, while maintaining professional specificity. Undergraduates demonstrated strengths in professionalism and academics, but showed deficiencies in community chronic disease management and management of key populations. These findings suggest the need to strengthen the training in health and social care to better align with the competencies required during standardized residency training.

Objective:To investigate the effect of interaction between body mass index (BMI) and gender on the survival of advanced gastric cancer after immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 317 patients with advanced gastric cancer who were admitted to the Nanfang Hospital, Southern Medical University from November 2019 to October 2023 were collected. There were 205 males and 112 females, aged 56 (range, 21-79)years. All 317 patients were divided into three groups based on BMI of patients, including 58 cases with BMI <18.5 kg/m2 were classified as the low body mass group, 183 cases with BMI 18.5-24.0 kg/m2 were classified as the normal body mass group, and 76 cases with BMI >24.0 kg/m2 were classified as the overweight or obese group. Patients included in the study were treated with a programmed death-ligand 1 (PD-L1) based immunotherapy regimen for 3 cycles based on their specific conditions, and further decision was made whether to undergo radical surgery or continue comprehensive treatment after evaluating the efficacy. Observation indicators: (1) clinicopathological characteristics of patients; (2) follow-up and mortality status; (3) analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Comparison of measurement data with normal distribution among groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test. Comparison of count data among groups was conducted using the chi-square test. The Cox proportional hazard model was used for univariate and multivariate analyses. Nonlinear trend was analyzed using the restricted cubic spline (RCS) curve, and trend and correction graphs were created using the rcssci package (v1.0). Results:(1) Clinicopathological characteristics of patients. There was no significant difference in gender, age, Borrmann classification, Lauren classification, combined positive score of PD-L1, expression of human epidermal growth factor receptor 2, Epstein-Barr virus infection, carcino-embryonic antigen, CA19-9, CA72-4, alpha-fetoprotein, conversion surgery among the 3 groups of patients ( P>0.05), and there was a significant difference in mismatch repair combined with micro-satellite stability among the 3 groups of patients ( P<0.05). (2) Follow-up and mortality status. Of the 317 patients, 316 cases completed follow-up and 1 case in the overweight or obese group was lost to follow-up. The follow-up time of the 316 cases was 13.8(range, 0.9-48.2)months. During the follow-up, the number of death in the low body mass group, normal body mass group and overweight or obese group were 27, 70 and 31, respectively. (3) Analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Results of multivariate analysis showed that gender and BMI were independent factors affecting survival of patients with advanced gastric cancer after immunotherapy ( hazard ratio=0.066, 0.922, 95% confidence interval as 0.005-0.846, 0.855-0.994, P<0.05). Results of further analysis showed that the interaction between BMI and gender was an independent factor affecting survival of patients with advanced gastric cancer after immuno-therapy ( hazard ratio=1.152, 95% confidence interval as 1.024-1.296, P<0.05). Results of Cox regre-ssion analysis based on different gender showed that took patients of the normal body mass group as a reference, the male patients of the low body mass group had a significantly increased risk of death, showing a significant statistically difference ( hazard ratio=1.809, 95% confidence interval as 1.037-3.155, P<0.05). Results of RCS curve analysis showed that there was a non-linear correlation between BMI and survival of patients with advanced gastric cancer after immunotherapy ( P<0.05). Results of corrected RCS curve analysis using the rcssci package showed that there was a U-shaped relationship between BMI and survival of patients with advanced gastric cancer after immuno-therapy ( P<0.05), with the optimal cut-off value of BMI as 22.2 kg/m 2. Results of RCS curve analysis based on different gender showed that there was a U-shaped relationship between BMI and survival of male patients with advanced gastric cancer after immunotherapy ( P<0.05), with the optimal cut-off value of BMI as 22.7 kg/m 2. Conclusions:Gender, BMI and the interaction between BMI and gender are independent factors affecting survival of patients with advanced gastric cancer after immuno-therapy. There is a U-shaped relationship between BMI and survival of patients, with the optimal cut-off value of BMI as 22.2 kg/m 2, and there is a U-shaped relationship between BMI and survival of male patients, with the optimal cut-off value of BMI as 22.7 kg/m 2.

Objective:To investigate the impact of hysteroscopic surgery on fresh embryo transfer outcomes in patients with transvaginal ultrasound-diagnosed FIGO Type Ⅱ/Ⅲ uterine fibroids that may affect the uterine cavity morphology, providing a reference for clinical practice.Methods:A retrospective cohort study was performed to analyze the clinical data of 346 patients who visited the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Peking University Third Hospital between January 2020 and December 2022, with transvaginal ultrasound findings indicating uterine fibroids adjacent to or protruding into the uterine cavity (FIGO Type Ⅱ, Ⅲ) and who underwent fresh embryo transfer. Patients were divided into two groups based on whether hysteroscopic surgery were performed: the hysteroscopic surgery group ( n=237, the group that underwent hysteroscopy before embryo transfer) and the non-surgery group ( n=109, the group that proceeded directly to embryo transfer without hysteroscopy). Basic patient characteristics and pregnancy outcomes were compared between the two groups. Multivariate logistic regression analysis was used to identify factors influencing clinical pregnancy rate and live birth rate. Results:The baseline characteristics showed no statistically significant differences between the two groups. The clinical pregnancy rate [44.3% (105/237)] and the live birth rate [32.5% (77/237)] following fresh embryo transfer in the hysteroscopic surgery group were significantly higher than those in the non-surgery group [31.2% (34/109), P=0.021; 18.3% (20/109), P=0.007], whereas the pregnancy loss rate showed no significant difference. Stratified analysis by age revealed that for patients aged <35 years, the clinical pregnancy rate [62.1% (54/87)] and the live birth rate [51.7% (45/87)] in fresh embryo transfer cycles were significantly higher in the hysteroscopic surgery group compared with the non-surgery group [30.8% (12/39), P=0.001; 25.6% (10/39), P=0.006]. Multivariate logistic regression analysis further confirmed that hysteroscopic surgery was an independent factor influencing live birth rate ( OR=2.128, 95% CI: 1.152-3.930, P=0.016). Among patients aged <35 years, hysteroscopic surgery was an influencing factor of both clinical pregnancy rate ( OR=4.222, 95% CI: 1.745-10.215, P=0.001) and live birth rate ( OR=3.449, 95% CI: 1.436-8.282, P=0.006). Conclusion:For infertile patients with ultrasound findings of uterine fibroids adjacent to or protruding into the uterine cavity, especially younger patients, hysteroscopy is recommended. It can improve pregnancy outcomes of fresh embryo transfer, increasing both the clinical pregnancy rate and the live birth rate.

Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.