Objective:To investigate the correlation of epithelial lesions among different biopsy sites in the female lower genital tract and the relationship between age and lesion distribution.Methods:A total of 406 148 patients with cervical biopsy specimens archived at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2021 were analyzed. Among them, 70 309 cases (17.31%) had concurrent vaginal biopsies, and 16 073 cases (3.96%) had concurrent vulvar biopsies. (1) Cases were divided into four 3-year intervals to compare vaginal or vulvar biopsy rates and high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL +) detection rates across time periods. (2) Correlations between cervical lesions and vaginal or vulvar lesions were assessed. (3) Patients were stratified into three age groups (<30, 30-49, and ≥50 years) to compare vaginal or vulvar HSIL + detection rates. Results:Mean ages of patients with cervical, vaginal, and vulvar biopsies were (41.3±11.0), (47.4±12.5), and (41.9±13.2) years, respectively. Patients with vaginal biopsy were significantly older than cervical or vulvar groups (all P<0.001). (1) Vaginal biopsy rates increased markedly from 7.37% (2010—2012) to 22.76% (2019—2021; χ2=9 205.01, P<0.001); vulvar biopsy rates increased slightly from 2.80% to 5.69% ( χ2=1 777.25, P<0.001). Correspondingly, vaginal HSIL + detection rates rose from 0.28% to >0.5% (0.56% in 2013—2015, 0.59% in 2016—2018, 0.51% in 2019—2021; χ2=134.70, P<0.001), while vulvar HSIL + rates increased from 0.03% to 0.33% ( χ2=56.54, P<0.001). (2) Weak correlation existed between cervical and vaginal lesions ( r=0.28; P<0.001; n=70 309), while cervical-vulvar correlation was weaker ( r=0.22, P<0.001; n=16 073). (3) Vaginal HSIL + detection rates were higher in cervical HSIL + patients aged 30-49 years (26.65%) and ≥50 years (26.79%) versus <30 years (14.63%; both P<0.001). Conversely, vulvar HSIL + detection rates were higher in the <30 years group (23.08%) versus 30-49 years (13.83%) and ≥50 years (12.89%; both P<0.05). Conclusions:Vaginal or vulvar lesion detection rates increase with biopsy frequency. Vaginal lesions correlate with cervical abnormalities, whereas vulvar lesions are relatively independent. In cervical HSIL + patients, those <30 years are more prone to have vulvar HSIL +, while those ≥30 years show higher vaginal HSIL + incidence. These age-specific distribution patterns inform optimized biopsy strategies.

Diabetic nephropathy(DN)is a significant causative factor of end-stage renal disease globally,and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways.Podocytes play crucial roles in the process of DN,with the extent of podocyte injury closely associated with key pathological manifestations of renal damage,such as proteinuria,glomerular filtration rate,and glomerulosclerosis.However,due to the complexity and interplay of mechanisms contributing to podocyte injury,such as oxidative stress,abnormal lipid metabolism,and mitochondrial damage,the precise mechanisms underlying podocyte injury remain incompletely understood.This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN.Furthermore,this article summarized the implications of these mechanisms for DN treatment,particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways,so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.

Objective:To investigate the correlation of epithelial lesions among different biopsy sites in the female lower genital tract and the relationship between age and lesion distribution.Methods:A total of 406 148 patients with cervical biopsy specimens archived at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2021 were analyzed. Among them, 70 309 cases (17.31%) had concurrent vaginal biopsies, and 16 073 cases (3.96%) had concurrent vulvar biopsies. (1) Cases were divided into four 3-year intervals to compare vaginal or vulvar biopsy rates and high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL +) detection rates across time periods. (2) Correlations between cervical lesions and vaginal or vulvar lesions were assessed. (3) Patients were stratified into three age groups (<30, 30-49, and ≥50 years) to compare vaginal or vulvar HSIL + detection rates. Results:Mean ages of patients with cervical, vaginal, and vulvar biopsies were (41.3±11.0), (47.4±12.5), and (41.9±13.2) years, respectively. Patients with vaginal biopsy were significantly older than cervical or vulvar groups (all P<0.001). (1) Vaginal biopsy rates increased markedly from 7.37% (2010—2012) to 22.76% (2019—2021; χ2=9 205.01, P<0.001); vulvar biopsy rates increased slightly from 2.80% to 5.69% ( χ2=1 777.25, P<0.001). Correspondingly, vaginal HSIL + detection rates rose from 0.28% to >0.5% (0.56% in 2013—2015, 0.59% in 2016—2018, 0.51% in 2019—2021; χ2=134.70, P<0.001), while vulvar HSIL + rates increased from 0.03% to 0.33% ( χ2=56.54, P<0.001). (2) Weak correlation existed between cervical and vaginal lesions ( r=0.28; P<0.001; n=70 309), while cervical-vulvar correlation was weaker ( r=0.22, P<0.001; n=16 073). (3) Vaginal HSIL + detection rates were higher in cervical HSIL + patients aged 30-49 years (26.65%) and ≥50 years (26.79%) versus <30 years (14.63%; both P<0.001). Conversely, vulvar HSIL + detection rates were higher in the <30 years group (23.08%) versus 30-49 years (13.83%) and ≥50 years (12.89%; both P<0.05). Conclusions:Vaginal or vulvar lesion detection rates increase with biopsy frequency. Vaginal lesions correlate with cervical abnormalities, whereas vulvar lesions are relatively independent. In cervical HSIL + patients, those <30 years are more prone to have vulvar HSIL +, while those ≥30 years show higher vaginal HSIL + incidence. These age-specific distribution patterns inform optimized biopsy strategies.

Objective:To examine the factors that contribute to memory impairment in elderly stroke patients and develop a predictive model.Methods:One hundred stroke patients from the First People's Hospital of Changzhou were selected to assess the incidence of memory impairment using the Montreal cognitive assessment memory index score(MoCA-MIS).Univariate analysis and multivariate Logistic regression were performed to determine the factors influencing memory impairment in these patients.Additionally, the correlation among relevant scale scores was examined, and a prediction model was developed.Results:In the study, 49 patients(49.0%)did not exhibit memory impairment.Patients with memory impairment were found to have higher proportions of individuals over 75 years old, elevated levels of triglyceride(TG), total cholesterol(TC), low-density lipoproteins cholesterol(LDL-C), and National Institute of Health Stroke Scale(NIHSS)scores compared to those without memory impairment.Conversely, patients without memory impairment had higher proportions of individuals with more than 9 years of education, higher levels of high-density lipoprotein cholesterol(HDL-C), mini-mental state examination(MMSE)scores, Rivermead behavioural memory test-Ⅱ(RBMT-Ⅱ)scores, and picture-based memory impairment screen(PMIS)scores(all P<0.05).Furthermore, Montreal cognitive assessment-memory index(MoCA-MIS)scores in stroke patients with memory impairment showed negative correlations with NIHSS scores, TG, and LDL-C, while showing positive correlations with HDL-C, MMSE scores, RBMT-Ⅱ scores, and PMIS scores(all P<0.05).Multifactorial Logistic regression analysis indicated that years of education, TG, HDL-C, NIHSS score, MMSE score, RBMT-Ⅱ score, PMIS score, and the location of the lesion in the cortex or temporal lobe were significant factors influencing memory impairment in stroke patients(all P<0.05).The receiver operating characteristic curve(ROC)analysis revealed an area under curve(AUC)of 0.955(95% CI: 0.921-0.977)for the prediction model of memory impairment in stroke patients, with a Yoden index of 0.841. Conclusions:The risk of memory impairment in stroke patients is associated with education years and blood lipid levels.Factors such as high education level, active cognitive function, and memory training serve as protective factors against memory impairment.The prediction model developed using these influencing factors demonstrates high predictive accuracy for post-stroke memory impairment.

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the validity of a function assessing tool based on the International Classification of Functioning, Disability and Health′s (ICF′s) rehabilitation set in assessing aging-related disability.Methods:A total of 1610 elderly people from 15 nursing homes across China were assessed using the tool based on the ICF′s rehabilitation set and with the 12-item short form health survey (SF-12). The structural validity of the responses was analyzed using factor analysis, and criterion-related validity was also evaluated.Results:The factor analysis yielded three factors with eigenvalues greater than 1. Their cumulative explanatory power was 74.4%. Item d550 eating had double loading in the factor analysis. The item scores and the total scores of the disability assessment tool were significantly negatively correlated with the physiological function domain scores and the psychological function domain scores.Conclusion:The function assessment tool based on the ICF′s rehabilitation set when combined with a numerical rating scale has good structural and criterion-related validity in the assessment of disability due to aging.