Objective To analyze the influencing factors of pancreatic fat deposition in patients with type 2 diabetes mellitus (T2DM), and to explore the relationship between pancreatic fat deposition and islet function. Methods A survey on diabetes prevalence was conducted among 548 residents in the Nicheng community of Pudong New Area from October 2015 to December 2016, including 301 patients with T2DM and 247 subjects with normal glucose tolerance (NGT). General information of the subjects were recorded, blood biochemical and insulin indexes were measured, body composition was measured by dual-energy X-ray absorptiometry, and insulin resistance index (HOMA-IR) and islet cell sensitivity index (HOMA-β) were calculated. Fatty liver and pancreatic fat deposition were detected by ultrasound. Both the T2DM group and NGT group were further divided into two subgroups according to the pancreatic fat deposition. Differences in general demographic information, biochemical and body fat indices among the groups were compared. Multivariate logistic regression was used to analyze the influencing factors of pancreatic fat deposition. Results In the NGT group, the subgroup with pancreatic fat deposition showed higher levels of age, waist circumference, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin levels (FINS), 2-hour postprandial insulin levels (2 h INS), triglycerides (TG), uric acid (UA), alanine aminotransferase (ALT), fatty liver prevalence, abdominal fat percentage, and abdomen-to-hip ratio (AHR), compared with the subgroup without pancreatic fat deposition. High-density lipoprotein cholesterol (HDL-C) and limb fat percentage were lower in the subgroup with pancreatic fat deposition. In the T2DM group, the subgroup with pancreatic fat deposition showed higher levels of waist circumference, BMI, FINS, 2 h INS, TG, UA, ALT, aspartate aminotransferase (AST), fatty liver prevalence, and abdominal fat percentage, compared with the subgroup without pancreatic fat deposition, with statistically significant differences (P<0.05). The HOMA-IR and HOMA-β in both NGT and T2DM groups with pancreatic fat deposition were significantly higher than those in the groups without pancreatic fat deposition. The prevalence of insulin resistance also significantly increased, with statistically significant differences (P<0.05). The results of multivariate logistic regression analysis showed that HDL-C, HOMA-β, abdominal fat percentage, age and fatty liver were the influencing factors for pancreatic fat deposition in NGT. Conclusion Elderly individuals with abdominal obesity and fatty liver are more prone to developing pancreatic fat deposition, which can affect islet function and aggravate the insulin resistance.

Objective To elucidate the molecular genetic etiology of patients with disorders of sex development (DSD) using whole exome sequencing (WES), thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities. Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021, with an additional family study for one proband. Genomic DNA was extracted from patients for WES analysis. Single nucleotide polymorphism (SNP) and insertions/deletion (InDel) tests were identified using SAMtools software in conjunction with established SNP and InDel databases. Copy number variations (CNVs) at the exon level were detected using ExomeDepth, while the potential pathogenicity of mutations was predicted with PolyPhen-2, Mutation taster and PyMol software, with Sanger sequencing employed for confirmation. Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD. Among the 46,XX DSD patients, the SRY gene was detected in 14 patients. In the remaining 8 patients and a proband's families, single nucleotide site variations (SNVs) of NR5A1, PROKR2 and ANOS1 genes were identified in 2 patients, and CNVs in CYP21A2 gene were found in 4 patients. The pathogenicity of CYP21A2 EX1 Dup has been previously reported, while the remaining 3 CNVs were of uncertain significance, and no DSD-related mutations were detected in 2 patients. In the WES analysis of 46,XY DSD patients, 10 pathogenic or likely pathogenic SNVs across 5 genes (SRY, AR, SRD5A2, CYP17A1, and NR5A1) were identified in 14 patients. Additionally, 5 likely pathogenic CNVs involving the CYP21A2, AKR1C2, CBX2, and NR5A1 genes were detected in 5 patients, comprising 3 deletions and 2 duplications. Novel SNVs in NR5A1 (c.722G>T, c.48C>G) and ANOS1 c.564A>T were identified, with no prior reports in relevant databases. The pathogenicity of CYP21A2 EX1 Dup is documented in related databases, while the remaining CNVs have not been previously reported. Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD, broadened the spectrum of known DSD-related gene mutations, and deepened our comprehension of DSD pathogenesis, offering valuable support for genetic counseling.

Neuro-developmental disorders (NDDs) are chronic developmental brain dysfunctions that affect multifunctional areas of the brain,caused by various genetic or acquired factors. Vitamin D (Vit D), as a neurosteroid hormone, can exert its function through both genetic and non-genetic mechanisms. Over the past few decades, studies on the relationship between Vit D levels and NDDs have found that Vit D deficiency during development is a risk factor for some NDDs. Vit D deficiency in early life can affect brain development, disrupt the balance of neurotransmitters in the brain, and reduce the body's and brain's antioxidant capacity. This review examines the mechanism of Vit D in the brain, explores the relationship between Vit D and neurodevelopmental disabilities, highlights recent research progress and identifies unsolved problems, in order to deepen understanding of the role of Vit D in NDDs and provide novel insights for the diagnosis and treatment of NDDs.

Objective To investigate the relationship between appendicular skeletal muscle composition (muscle mass and muscle index) and glycosylated hemoglobin A_1c (HbA_1c) level in type 2 diabetes mellitus (T2DM) patients. Methods A total of 459 adult T2DM patients hospitalized in the Department of Endocrinology, Tangdu Hospital of Air Force Medical University from April 2021 to June 2022 were selected as the research objects. Bioelectrical impedance analysis was used to evaluate the body composition of the patients. The patients were divided into two groups according to HbA_1c level: standard glycation group (HbA_1c ≤7.0%, n=145) and unqualified glycation group (HbA_1c >7.0%, n=314). The two groups' general data, biochemical indexes, muscle content, fat content and other body composition were analyzed. Spearman correlation analysis and multiple logistic regression analysis were used to analyze the relationship between body composition and glycemic control in type 2 diabetic patients. Results The appendicular skeletal muscle mass and its index (ASMI) of the patients in the standard glycation group were better than those in the unqualified glycation group (P<0.05). However, there were no significant differences in gender, history of antidiabetic drugs and body fat (body fat content, limb fat content and visceral fat content) between the two groups (P>0.05). Spearman correlation analysis showed that appendicular skeletal muscle mass and its index were negatively correlated with HbA_1c (r=-0.158, P=0.001; r=-0.187, P<0.001). Logistic regression analysis showed that upper limb skeletal muscle mass (OR=3.570, 95%CI 2.293-5.559) and lower limb skeletal muscle mass (OR=1.297, 95%CI 1.146-1.468) were independent protective factors for achieving glycation standard in HbA_1c group. Conclusions The skeletal muscle mass of limbs is a protective factor for reaching the standard of HbA_1c. With the increase of skeletal muscle mass of limbs, the level of HbA_1c gradually decreases. Among them, the increase of upper limb muscle mass has a stronger correlation with reaching the standard of HbA_1c.

Objective To investigate factors influencing the occurrence of early haematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (sICH), to develop a predictive model and evaluate its predictive efficacy. Methods A retrospective cohort of 238 patients with sICH, admitted to General Hospital of Western Theater Command between January 2017 and December 2022, was analyzed. Patients were categorized into two groups based on the criteria of HE exceeding 33% in relative volume or 6 ml in absolute volume: HE group (n=62) and non-haematoma expansion (NHE) group (n=176). Clinical characteristics, laboratory findings, Non-contrast Computed Tomography (NCCT) imaging, and Glasgow Coma Scale (GCS) scores were compared between the two groups. Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence. The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients, Additionally, the related clinical, NCCT, and GCS models were constructed. The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic (ROC) curve (AUC), and the clinical application value of each model was assessed using accuracy, sensitivity, specificity, and Jordon's index. The Delong test was applied to analyze differences in the predictive values of the models. Results Significant differences in satellite sign, vortex sign, and history of anticoagulant treatment were observed between two groups (P<0.05). Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients, including the first CT examination time, homogeneity, history of anticoagulant medication, volume, maximal diameter, hypodensity sign, island sign, satellite sign, and vortex sign (P<0.05). The AUCs for the constructed clinical model, NCCT model, GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672, 0.706, 0.518 and 0.754, respectively. The nomogram model demonstrated higher accuracy, sensitivity, Jordon's index and AUC compared with those in the clinical and NCTT models. Conclusions The first CT examination time, homogeneity, history of anticoagulant treatment, volume, maximum diameter, hypodensity sign, island sign, satellite sign, and vortex sign are independent predictors of early HE in sICH patients. The nomogram model, constructed with the above parameters, demonstrated high predictive efficacy for HE and holds potential for clinical application.

Objective To investigate the effect and mechanism of lycium barbarum polysaccharide (LBP) on hepatocyte injury induced by homocysteine (Hcy). Methods Normal C3H/An mouse hepatocytes (NCTC 1469) were cultured in vitro and treated with different concentrations of Hcy (0, 50, 100, 200, 500 μmol/L). The optimal concentrations of Hcy-treated NCTC 1469 cells were detected by MTT assay. When the cells reached the logarithmic growth stage, the conditions were set up as follows: (1) control group (cultured with DMEM medium supplemented with 10% horse serum) and Hcy group (treated with 100 μmol/L Hcy solution for 48 h), and the cells were collected. Cell viability staining was used to detect apoptosis, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activity detection kit was used to detect AST and ALT activities, RT-qPCR was used to detect the expression levels of YAP1, DNMT1, DNMT3a and DNMT3b mRAN, and Western blotting was used to detect the expression of YAP1 protein, nested methylation specific PCR (nMS-PCR) was used to detect DNA methylation rates in the YAP1 promoter region. (2) Control group, LBP group, Hcy group and Hcy+LBP group. LBP group was treated with 4 mg/ml LBP solution for 2 h, Hcy group and Hcy+LBP group were treated with 100 μmol/L Hcy solution for 48 h, and Hcy+LBP group was treated with 4 mg/ml LBP solution at 46 h, and the cells were collected. The expression levels of YAP1, DNMT1, DNMT3a and DNMT3b mRAN were detected by RT-qPCR; the expression of YAP1, Bax and Bcl-2 proteins was detected by Western blotting; AST/ALT activity detection kit was used to detect AST and ALT activities. Prediction of DNA methylation CpG islands in YAP1 promoter region by bioinformatics. Results NCTC 1469 cells were treated with 100 μmol/L Hcy according to the results of MTT assay. Compared with control group, the apoptosis rate of Hcy group increased (P<0.01), the activities of ALT and AST increased (P<0.001), the mRAN and protein expression levels of YAP1 decreased (P<0.001), and the methylation rate of YAP1 promoter region increased (P<0.01), the mRNA expression levels of DNMT1, DNMT3a and DNMT3b increased (P<0.01 or P<0.001). Compared with Hcy group, the mRNA expression levels of DNMT1, DNMT3a and DNMT3b in the Hcy+LBP group decreased (P<0.001), the mRAN and protein expression levels of YAP1 significantly increased (P<0.01 or P<0.001). In addition, in the Hcy+LBP group, cells showed significantly elevated of Bcl-2 protein (P<0.001), but decreased Bax protein (P<0.001), and decreased activities of ALT and AST (P<0.001). Conclusions The decrease of YAP1 expression may be the key process of Hcy induced injury of NCTC 1469 cells, and the methylation of the YAP1 promoter region may be the molecular mechanism of Hcy induced YAP1 expression change. LBP may improve NCTC 1469 cell damage induced by Hcy by positively regulating YAP1 expression.

Objective To observe the effects of Wuzi Yanzong Pill (WYP) on motor function in a mouse model of Parkinson's disease (PD) and to explore its potential mechanisms. Methods Twenty-four male C57BL/6 mice were randomly divided into control group, model group and WYP group, with 8 mice in each group. Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model. From the 1st day of model preparation, mice in WYP group were gavaged with WYP solution [16 g/(kg·d)] twice daily for 14 consecutive days. At the same time, mice in control group and model group were gavaged with 0.9% NaCl solution [50 ml/(kg·d)] twice a day. Gait experiment was utilized to assess the behavioral performance of mice in each group. Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra region, the fluorescence intensity of nuclear factor E2-related factor 2 (Nrf2), and the number of NeuN neurons co-labeled with Nrf2 in each group. Western blotting was employed to determine the expression levels of TH, Kelch-like ECH-associated protein 1 (Keap-1), Nrf2, and heme oxygenase-1 (HO-1) in the brain tissue of mice in each group. Results The gait experiment results showed that, compared with control group, standing time of the left front paw, right front paw, left hind paw, and right hind paw of the mice in model group was significantly shortened (P<0.01), while swinging time of the left front paw, right front paw, left hind paw, and right hind paw was significantly prolonged (P<0.05). Compared with model group, standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged (P<0.05), while swing time of the left front paw and right front paw was significantly shortened (P<0.05). Immunofluorescence staining and Western blotting results showed that, compared with control group, in model group the number of TH-positive cells, average fluorescence intensity of Nrf2, and HO-1 levels decreased (P<0.01), while the Keap-1 protein level increased (P<0.01), and the number of Nrf2 expression on NeuN neurons decreased (P<0.001). Compared with model group, the number of TH-positive cells, average fluorescence intensity of Nrf2, HO-1 level, and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased (P<0.05), while Keap-1 protein level decreased (P<0.05). Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice. The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

Objective To investigate the effects and mechanism of β₂ adrenergic receptors (ADRB2) in ferroptosis and autophagy induced by erastin (Era) in prostate cancer. Methods PC-3 cells were infected with lentivirus or control and set to sh-NC group (normal culture), sh-NC+Era group (10 μmol/L Era treatment for 24 h), sh-ADRB2 group (normal culture), and sh-ADRB2+Era group (10 μmol/L Era treatment for 24 h). The viability of the cells treated with Era and ferrostatin-1 (Fer-1) was measured by CCK-8 assay. The cell morphology was analyzed by transmission electron microscopy. The malondialdehyde (MDA) content was measured by the Lipid Oxidation Detection Kit and the iron level by Iron Colorimetric Assay. Western blotting was used to detect the expressions of cystine-glutamate exchanger (XCT), ferritin heavy chain 1 (FTH1), glutathione peroxidase 4 (GPX4), p62, LC3, JNK, c-Jun, and p-c-Jun. PC-3 cells with ADRB2 knockdown were injected into nude mice to construct a xenograft model and then treated with Era. The animals were divided into sh-NC group, sh-NC+Era group, sh-ADRB2 group, and sh-ADRB2+Era group, with 4 mice in each group. The tumor volumes were recorded every other day and the final tumor weight was measured at study termination. The expressions of ADRB2, JNK, c-Jun, and p-c-Jun were detected by immunohistochemistry (IHC). Results The viability of PC-3 cells decreased after Era treatment (P<0.01) and recovered after Fer-1 treatment (P<0.01). Morphological changes of ferroptosis and autophagy were observed in Era-treated cells, and MDA and iron ion contents up-regulated (P<0.05 or P<0.01). Knockdown of ADRB2 and Era treatment further inhibited PC-3 cell viability (P<0.05), and MDA and iron ion contents up-regulated (P<0.01). The expressions of ferroptosis-related proteins FTH1, XCT, GPX4, and LC3 down-regulated (P<0.05 or P<0.05), p62 and JNK pathway-related proteins JNK, c-Jun, and p-c-Jun were up-regulated (P<0.01). After JNK inhibitor treatment, the expressions of FTH1, XCT, and LC3 increased, and p62 decreased (P<0.01). In the PC-3 xenograft model, tumor volume in sh-ADRB2+Era group was significantly smaller than those in sh-NC+Era group and sh-ADBR2 group (P<0.05 or P<0.01). IHC showed that compared with sh-NC group, ADRB2 protein expression level was down-regulated in sh-ADRB2 group (P<0.05), while JNK, c-Jun, and p-c-Jun protein expression levels were elevated (P<0.01). Compared with sh-NC+Era group, the ADRB2 protein expression level in sh-ADRB2+Era group was down-regulated, while JNK, c-Jun, and p-c-Jun protein expression levels were up-regulated (P<0.05). Conclusion ADRB2 regulated ferroptosis and autophagy induced by Era via JNK/c-Jun pathway in prostate cancer.

Objective To analyze the changes of B lymphocyte (B cells) subsets in peripheral blood of patients with chronic hepatitis B (CHB) and to explore its clinical significance. Methods Peripheral blood samples were collected from 37 treatment-naïve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022, and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls (HC). The study subjects' clinical indexes such as age, HBV DNA viral load, HBsAg quantification, HBeAg semi quantification, ALT, AST, and AST/ALT ratio were collected. The change characteristics of the frequency, phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC. Using multi-color flow cytometry, and the correlation between them and clinical indexes was analyzed. Results Frequency analysis of each subset of B cells showed that compared with HC, the frequency of total B cells, transitional B cells and naive B cells was decreased (P<0.05), while the frequency of mature B cells, memory B cells, atypical memory B cells and activated memory B cells was increased in CHB patients (P<0.01). And there was no significant difference in the frequency of resting memory B cells between the two groups (P>0.05). The results of functional analysis showed that compared with HC, the expression levels of CD79b on total B cells, mature B cells, memory B cells, naive B cells, activated memory B cells, atypical memory B cells and resting memory B cells in CHB patients were increased (P<0.05). The expression level of programmed cell death protein-1(PD-1) on atypical memory B cells in CHB patients was also higher than that in HC group (P<0.05). The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age (r=-0.39, P<0.05), while the expression of programmed death-1 (PD-1) on total B cells, mature B cells, transitional B cells, memory B cells and naive B cells were slightly positively correlated with age (r>0.36, P<0.05). Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients, and age is a potential risk factor for the decline in humoral immune function in CHB patients.

Objective To compare the efficacy and safety between hypofractionated radiotherapy (HyRt) and conventional radiotherapy after breast-conserving surgery. Methods This study was a single-center, prospective, randomized controlled study. Eighty-three patients with pTis-T₂N₀M₀ breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included. The patients received breast-conserving surgery + sentinel lymph node biopsy (SLNB). After surgery, they were treated with intensity modulated radiation therapy (IMRT). According to random table method, patients were divided into HyRt group (n=41) and conventional radiotherapy group (n=42). The dose of organs at risk, treatment efficacy, treatment failure modes, and radiotherapy related adverse reactions were analyzed in the two groups. The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0, including radiation dermatitis, radiation pneumonia, breast/skin fibrosis, pulmonary fibrosis, etc. Results Eighty-three patients with breast cancer were included, with a median age of 44 (26-67) years. There was no statistically significant difference in clinical parameters such as age (P=0.443), TNM stage (P=0.335), molecular typing (P=0.333), degree of differentiation (P=0.617), and pathological type (P=0.127) between the two groups of patients. Compared with conventional radiotherapy group, the V5 (25.6% vs. 33.8%, P=0.015), V20 (13.3% vs. 17.2%, P=0.042), and the mean radiation dose (MLD; 7.4 Gy vs. 10.4 Gy, P=0.020) of the affected lung of HyRt group significantly decreased. Only 3 patients in this study experienced distant metastasis, and no regional lymph node metastasis or local recurrence was observed. There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group (94.4% vs. 85.2%, P=0.818). Compared with conventional radiotherapy group, the incidence of ≥ grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced (2.4% vs. 21.4%, P=0.015). There was no difference in the incidence of grade Ⅰ breast/skin fibrosis (19.5% vs. 14.3%, P=0.570) between the two groups, and no grade Ⅲ radiotherapy-related side effects were observed in the two groups. Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy, the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions. HyRt can be used as the first option of radiation therapy.