Chronic cerebral hypoperfusion (CCH) plays an important role in the occurrence and development of vascular dementia (VD). Recent studies have indicated that multiple stages of immune-inflammatory response are involved in the process of cerebral ischemia, drawing increasing attention to immune therapies for cerebral ischemia. This study aims to identify potential immune therapeutic targets for CCH using bioinformatics methods from an immunological perspective. We identified a total of 823 differentially expressed genes associated with CCH, and further screened for 9 core immune-related genes, namely RASGRP1, FGF12, SEMA7A, PAK6, EDN3, BPHL, FCGRT, HSPA1B and MLNR. Gene enrichment analysis showed that core genes were mainly involved in biological functions such as cell growth, neural projection extension, and mesenchymal stem cell migration. Biological signaling pathway analysis indicated that core genes were mainly involved in the regulation of T cell receptor, Ras and MAPK signaling pathways. Through LASSO regression, we identified RASGRP1 and BPHL as key immune-related core genes. Additionally, by integrating differential miRNAs and the miRwalk database, we identified miR-216b-5p as a key immune-related miRNA that regulates RASGRP1. In summary, the predicted miR-216b-5p/ RASGRP1 signaling pathway plays a significant role in immune regulation during CCH, which may provide new targets for immune therapy in CCH.
Humans ; Computational Biology/methods* ; Brain Ischemia/therapy* ; Immunotherapy ; MicroRNAs/genetics* ; Signal Transduction ; Dementia, Vascular/genetics* ; Chronic Disease

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Abstract Prevention and control of myopia requires comprehensive measures. Based on the system established earlier, the system is revised and upgraded. The original system emphasizes comprehensive measures and proposes to focus on both the symptoms and root causes. These measures are summarized into six aspects, three address the root cause measures including health education, glasses optics and visual environment, and three address symptoms measures including eye exercises, physical therapy and drugs. The paper is comprehensively supplemented and analyzes the primary and the secondary, and promotes physical therapy from treating the symptoms to treat both the symptoms and the root causes. These improvement measures will help promote the prevention and control of myopia in children and adolescents.

Objective:To explore the clinical application value of magnetic stimulation combined with biofeed-back technology in female stress urinary incontinence(SUI).Methods:Sixty mild or moderate female SUI patients who underwent rehabilitation treatment at the Pelvic Floor Rehabilitation Center of Nanjing Women and Children's Healthcare Hospital from July to December 2021 were collected and randomly divided into two groups,with 30 pa-tients in each group.The observation group received a treatment protocol of electrical stimulation+biofeedback therapy(electric combined group)and the other group received a treatment protocol of magnetic stimulation+bi-ofeedback therapy(magnetic combined group).The treatment course for both groups consisted of 12 sessions.The Sandvik severity Index(urinary incontinence),the amount of u 1-hoururine leakage,pelvic floor muscle strength,pelvic floor muscle electrophysiological indices,the degree of urinary incontinence impact(ⅡQ-7 score)and the treatment efficacy were assessed and compared before and after the treatment in the two groups.Re-sults:Compared with the pre-treatment,the Sandvik Severity Index,the 1-hour urine leakage,and the n Q-7 score decreased in the magnetic combined group and the electric combined group after treatment,while the mus-cle strength of type Ⅰ,type Ⅱ,maximum of fast muscle,and mean value of slow muscle increased significantly,and the differences were statistically significant(P＜0.05).The difference between the above indexes was not statistically significant when comparing the magnetic combined group and the electric combined group after treat-ment(P＞0.05),and the treatment efficiency of the electric combined group was 93.33％and that of the magnet-ic combined group was 96.67％,and there was no statistical significance when comparing the efficiency of the two groups(P＞0.05).Conclusions:Magnetic stimulation combined with biofeedback technology has high thera-peutic efficiency for mild or moderate SUl,and is an optional rehabilitation technique for women with SUI.

Objective:To explore the clinical application value of magnetic stimulation combined with biofeed-back technology in female stress urinary incontinence(SUI).Methods:Sixty mild or moderate female SUI patients who underwent rehabilitation treatment at the Pelvic Floor Rehabilitation Center of Nanjing Women and Children's Healthcare Hospital from July to December 2021 were collected and randomly divided into two groups,with 30 pa-tients in each group.The observation group received a treatment protocol of electrical stimulation+biofeedback therapy(electric combined group)and the other group received a treatment protocol of magnetic stimulation+bi-ofeedback therapy(magnetic combined group).The treatment course for both groups consisted of 12 sessions.The Sandvik severity Index(urinary incontinence),the amount of u 1-hoururine leakage,pelvic floor muscle strength,pelvic floor muscle electrophysiological indices,the degree of urinary incontinence impact(ⅡQ-7 score)and the treatment efficacy were assessed and compared before and after the treatment in the two groups.Re-sults:Compared with the pre-treatment,the Sandvik Severity Index,the 1-hour urine leakage,and the n Q-7 score decreased in the magnetic combined group and the electric combined group after treatment,while the mus-cle strength of type Ⅰ,type Ⅱ,maximum of fast muscle,and mean value of slow muscle increased significantly,and the differences were statistically significant(P＜0.05).The difference between the above indexes was not statistically significant when comparing the magnetic combined group and the electric combined group after treat-ment(P＞0.05),and the treatment efficiency of the electric combined group was 93.33％and that of the magnet-ic combined group was 96.67％,and there was no statistical significance when comparing the efficiency of the two groups(P＞0.05).Conclusions:Magnetic stimulation combined with biofeedback technology has high thera-peutic efficiency for mild or moderate SUl,and is an optional rehabilitation technique for women with SUI.

Objective:To explore the clinical application value of magnetic stimulation combined with biofeed-back technology in female stress urinary incontinence(SUI).Methods:Sixty mild or moderate female SUI patients who underwent rehabilitation treatment at the Pelvic Floor Rehabilitation Center of Nanjing Women and Children's Healthcare Hospital from July to December 2021 were collected and randomly divided into two groups,with 30 pa-tients in each group.The observation group received a treatment protocol of electrical stimulation+biofeedback therapy(electric combined group)and the other group received a treatment protocol of magnetic stimulation+bi-ofeedback therapy(magnetic combined group).The treatment course for both groups consisted of 12 sessions.The Sandvik severity Index(urinary incontinence),the amount of u 1-hoururine leakage,pelvic floor muscle strength,pelvic floor muscle electrophysiological indices,the degree of urinary incontinence impact(ⅡQ-7 score)and the treatment efficacy were assessed and compared before and after the treatment in the two groups.Re-sults:Compared with the pre-treatment,the Sandvik Severity Index,the 1-hour urine leakage,and the n Q-7 score decreased in the magnetic combined group and the electric combined group after treatment,while the mus-cle strength of type Ⅰ,type Ⅱ,maximum of fast muscle,and mean value of slow muscle increased significantly,and the differences were statistically significant(P＜0.05).The difference between the above indexes was not statistically significant when comparing the magnetic combined group and the electric combined group after treat-ment(P＞0.05),and the treatment efficiency of the electric combined group was 93.33％and that of the magnet-ic combined group was 96.67％,and there was no statistical significance when comparing the efficiency of the two groups(P＞0.05).Conclusions:Magnetic stimulation combined with biofeedback technology has high thera-peutic efficiency for mild or moderate SUl,and is an optional rehabilitation technique for women with SUI.

Objective:To explore the clinical application value of magnetic stimulation combined with biofeed-back technology in female stress urinary incontinence(SUI).Methods:Sixty mild or moderate female SUI patients who underwent rehabilitation treatment at the Pelvic Floor Rehabilitation Center of Nanjing Women and Children's Healthcare Hospital from July to December 2021 were collected and randomly divided into two groups,with 30 pa-tients in each group.The observation group received a treatment protocol of electrical stimulation+biofeedback therapy(electric combined group)and the other group received a treatment protocol of magnetic stimulation+bi-ofeedback therapy(magnetic combined group).The treatment course for both groups consisted of 12 sessions.The Sandvik severity Index(urinary incontinence),the amount of u 1-hoururine leakage,pelvic floor muscle strength,pelvic floor muscle electrophysiological indices,the degree of urinary incontinence impact(ⅡQ-7 score)and the treatment efficacy were assessed and compared before and after the treatment in the two groups.Re-sults:Compared with the pre-treatment,the Sandvik Severity Index,the 1-hour urine leakage,and the n Q-7 score decreased in the magnetic combined group and the electric combined group after treatment,while the mus-cle strength of type Ⅰ,type Ⅱ,maximum of fast muscle,and mean value of slow muscle increased significantly,and the differences were statistically significant(P＜0.05).The difference between the above indexes was not statistically significant when comparing the magnetic combined group and the electric combined group after treat-ment(P＞0.05),and the treatment efficiency of the electric combined group was 93.33％and that of the magnet-ic combined group was 96.67％,and there was no statistical significance when comparing the efficiency of the two groups(P＞0.05).Conclusions:Magnetic stimulation combined with biofeedback technology has high thera-peutic efficiency for mild or moderate SUl,and is an optional rehabilitation technique for women with SUI.

Objective:To explore the clinical application value of magnetic stimulation combined with biofeed-back technology in female stress urinary incontinence(SUI).Methods:Sixty mild or moderate female SUI patients who underwent rehabilitation treatment at the Pelvic Floor Rehabilitation Center of Nanjing Women and Children's Healthcare Hospital from July to December 2021 were collected and randomly divided into two groups,with 30 pa-tients in each group.The observation group received a treatment protocol of electrical stimulation+biofeedback therapy(electric combined group)and the other group received a treatment protocol of magnetic stimulation+bi-ofeedback therapy(magnetic combined group).The treatment course for both groups consisted of 12 sessions.The Sandvik severity Index(urinary incontinence),the amount of u 1-hoururine leakage,pelvic floor muscle strength,pelvic floor muscle electrophysiological indices,the degree of urinary incontinence impact(ⅡQ-7 score)and the treatment efficacy were assessed and compared before and after the treatment in the two groups.Re-sults:Compared with the pre-treatment,the Sandvik Severity Index,the 1-hour urine leakage,and the n Q-7 score decreased in the magnetic combined group and the electric combined group after treatment,while the mus-cle strength of type Ⅰ,type Ⅱ,maximum of fast muscle,and mean value of slow muscle increased significantly,and the differences were statistically significant(P＜0.05).The difference between the above indexes was not statistically significant when comparing the magnetic combined group and the electric combined group after treat-ment(P＞0.05),and the treatment efficiency of the electric combined group was 93.33％and that of the magnet-ic combined group was 96.67％,and there was no statistical significance when comparing the efficiency of the two groups(P＞0.05).Conclusions:Magnetic stimulation combined with biofeedback technology has high thera-peutic efficiency for mild or moderate SUl,and is an optional rehabilitation technique for women with SUI.