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.

Organoids are cell mini-clusters and three-dimensional (3D) micro-organs cultured and spontaneously developed under suspension culture condition in vitro, possessing the abilities of self-organize and differentiate into functional cells. They are powerful, and can partially mimic the cellular heterogeneity, structure and function of the original tissues or organs. Lung organoids (LOs) can be cultured and constructed from human pluripotent stem cells or adult stem/progenitor cells. Co-culture of LOs with immune cells can better reflect the overall picture of the immune response of lung tissue and the full spectrum of infection in vivo. This review compares characteristics of LOs with those common models for respiratory infectious diseases, including animal models, two-dimensional cell culture, lung-on-chip and precision-cut lung slices. We provide an overview of the construction method of LOs and their application progress on respiratory system infectious diseases caused by viruses, bacteria, mycobacteria, cryptosporidium, and other pathogens.

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.

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.

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 investigate the genotypic and phenotypic characteristics of AB type GM2 gangliosidosis (GM2-GLS) with onset during childhood. Methods The report analyzed the clinical data and gene detection results of a 4-year-old child with AB type GM2-GLS diagnosed by Trio whole exome detection in March 2022 admitted to the Department of Pediatrics of Guangxi Zhuang Autonomous Region People's Hospital. The clinical data and genetic testing results are analyzed. A literature review was also conducted on relevant studies published between 1991 and 2022 in the PubMed database. Results The results of Trio whole exome sequencing and Sanger verification showed that the GM2A gene carried two compound heterozygous mutations: c.158_159delTG and c.496G>A, which caused p.L53Rfs*3 frameshift mutation and p.G166R missense mutation, respectively. A total of 20 cases were reported in 22 articles. A total of 11 mutation types of GM2A gene were included in the ClinVar Database. Conclusions AB type GM2-GLS is a rare autosomal recessive lysosomal storage disease, and its gene test is helpful for definite diagnosis.

Histone deacetylases (HDACs) can deacetylate histones, leading to tighter DNA binding, and thereby playing a role in inhibiting gene transcription. On the contrary, histone deacetylase inhibitors (HDACis) can promote chromatin relaxation, enabling various transcription factors to bind specifically to DNA and activate transcription genes. Dental stem cells (DSCs) are human adult stem cells. These cells have the characteristics of less damage and low immune rejection during sampling, and are especially important seed cells in the process of osteogenesis, odontogenesis and other differentiation. A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation, signal transduction, regulation of cellular inflammation and other life processes. This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs, aiming to provide insights into the study of the interaction between HDACs and HDACis, and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.

Epilepsy is a chronic disease characterized by recurrent, sudden, and excessive synchronous discharge of neurons in the brain, leading to transient brain dysfunction, and inflammatory responses in specific regions within the central nervous system are common features of epilepsy. In recent years, there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy, which activates the unfolded protein response, then regulate and control nuclear factor kappa-B (NF-κB), efficiently induces glial cell activation through the release of pro-inflammatory signals, in turn affects epileptogenesis and seizures by triggering neuroinflammation. This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology, aiming to provide insights for a deeper understanding of epilepsy.

Officers and soldiers exposed to high temperature and high-humidity environments are highly susceptible to exertional heat illness and even heatstroke. Reports indicated that after conventional treatment, the heat endurance damage in officers/soldiers with exertional heat illness can persist for months or even years. Therefore, the Expert Group of Heatstroke Prevention and Treatment of Heatstroke of Chinese PLA has specially formulated a technical proposal for the reconstruction of heat endurance in officers/soldiers suffering from exertional heatstroke, aiming to provide a safeguard for reconstruction of heat endurance in affected personnel. This article mainly elaborates on the basic concepts, technical requirements, initiation timing, implementation assessment, and follow-up of the heat endurance reconstruction for officers/soldiers with exertional heatstroke.

Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1 (CYP27A1) in hepatocellular carcinoma (HCC), and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC. Methods The Cance Genome Atlas (TCGA) database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients. The samples were divided into CYP27A1 high-expression group (n=170) and low-expression group (n=170) based on the median expression of CYP27A1 in HCC, gene set enrichment analysis (GSEA) was performed to investigate gene sets associated with CYP27A1 expression. The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database. The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines, including two groups, namely control group (transfecting empty vector) and CYP27A1 over-expression group (transfecting CYP27A1 over-expressed vector). CCK-8, flow cytometer, and reactive oxygen species (ROS) fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability, apoptosis and ROS levels in HCC cells. Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes. Results Compared with the normal liver tissue, the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced (P<0.01). The expression of CYP27A1 was significantly correlated with sex, T stage, tumor grade and tumor stage of HCC patients (P<0.05). Compared to the CYP27A1 high-expression group, patients in CYP27A1 low-expression group had lower survival rate (P<0.01). GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group. The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3, whereas CYP27A1 was mainly located in mitochondria in HepG2. CYP27A1 over-expression attenuated cell viability (P<0.01), and reduced the ROS levels (P<0.05), whereas it had no effects on the apoptosis in HCC cells (P>0.05). The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated (P<0.05), while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated (P<0.05). Conclusions The expression of CYP27A1 was decreased in HCC, and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation, although the precise mechanism requires future educidation.