最新刊期
卷 49 ， 期 5 ， 2024
- “最新研究揭示，2型糖尿病患者四肢骨骼肌含量与糖化血红蛋白水平呈负相关，四肢肌肉含量增加有助于降低HbA1c水平，为糖尿病管理提供新视角。”
摘要：ObjectiveTo investigate the relationship between appendicular skeletal muscle composition (muscle mass and muscle index) and glycosylated hemoglobin A1c (HbA1c) level in type 2 diabetes mellitus (T2DM) patients.MethodsA 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 HbA1c level: standard glycation group (HbA1c ≤7.0%, n=145) and unqualified glycation group (HbA1c >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.ResultsThe 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 HbA1c (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 HbA1c group.ConclusionsThe skeletal muscle mass of limbs is a protective factor for reaching the standard of HbA1c. With the increase of skeletal muscle mass of limbs, the level of HbA1c gradually decreases. Among them, the increase of upper limb muscle mass has a stronger correlation with reaching the standard of HbA1c.关键词：diabetes mellitus, type 2;glycosylated hemoglobin;body composition analysis;skeletal muscle mass;skeletal muscle mass index- 96
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发布时间：2024-06-24 - “云南省第一人民医院通过全外显子组测序技术深入分析性发育异常患者，揭示了致病基因突变谱，为遗传咨询提供帮助。”
摘要：ObjectiveTo 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.MethodsRetrospective 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.ResultsThe 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.ConclusionThe 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.关键词：disorders of sex development;whole exome sequencing;diagnosis;heterogeneity- 47
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发布时间：2024-06-24 - “在原发性脑出血领域，专家构建了预测早期血肿扩大的列线图模型，为临床预测提供高效解决方案。”
摘要：ObjectiveTo 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.MethodsA 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.ResultsSignificant 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.ConclusionsThe 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.关键词：spontaneous cerebral hemorrhage;hematoma expansion;nomogram model;prediction;CT- 65
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发布时间：2024-06-24 - “最新研究发现，慢性乙型肝炎患者外周血B细胞亚群频率及功能发生显著变化，年龄是影响免疫功能的关键因素。”
摘要：ObjectiveTo 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.MethodsPeripheral 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.ResultsFrequency 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).ConclusionsChronic 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.关键词：hepatitis B virus;hepatitis B, chronic;B-lymphocytes;immunity, humoral;peripheral blood- 51
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发布时间：2024-06-24 - “最新研究显示，早期乳腺癌保乳术后采用大分割放疗(HyRt)与常规分割放疗相比，具有更好的耐受性和更低的不良反应发生率，为乳腺癌放射治疗提供了新的选择。”
摘要：ObjectiveTo compare the efficacy and safety between hypofractionated radiotherapy (HyRt) and conventional radiotherapy after breast-conserving surgery.MethodsThis 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.ResultsEighty-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.ConclusionsCompared 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.关键词：early breast cancer;breast-conserving surgery;hypofractionated radiotherapy;conventional radiotherapy- 36
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发布时间：2024-06-24 - “最新研究揭示，高龄、腹型肥胖及脂肪肝是2型糖尿病患者胰腺脂肪沉积的关键影响因素，可能进一步影响胰岛功能，加剧胰岛素抵抗。”摘要：ObjectiveTo 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.MethodsA 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.ResultsIn 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.ConclusionElderly 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.关键词：pancreatic fat deposition;diabetes mellitus, type 2;insulin resistance
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发布时间：2024-06-24 - “重庆新桥医院研究发现，重庆地区中枢神经系统感染病例数呈上升趋势，病原体多样，临床表现复杂。研究为早期精准诊断、治疗提供重要参考。”
摘要：ObjectiveTo investigate the epidemiological and clinical characteristics of 954 cases of central nervous system (CNS) infections in Chongqing.MethodsA retrospective analysis was conducted on 954 patients with CNS infectious disease diagnosed and treated in the Second Affiliated Hospital of Army Medical University from 2008 to 2021. The analysis encompassed pathogens, patient gender, age of onset, time of onset, urban-rural distribution, education level, occupational distribution, and other epidemiological characteristics. The clinical manifestations, the positive rate of metagenomic next-generation sequencing (mNGS), and prognosis were also analyzed.ResultsAmong the 945 cases of CNS infectious diseases, the pathogens were viruses in 393(41.2%), Mycobacterium tuberculosis in 361(37.8%), other bacteria in 108(11.3%), Cryptococcus in 75(7.9%), Treponema pallidum in 16(1.7%) and parasites in 1(0.1%). The number of CNS infection cases from 2015 to 2021 increased by 85.6% compared with that from 2008 to 2014 (620 vs. 334, P<0.001). There was no significant difference in seasonal distribution of pathogens (P>0.05). CNS infectious diseases were more prevalent in rural areas (58.0%, P<0.001), with a male-to-female ratio of 1.7:1.0, and a higher incidence in individuals aged between 35 and 60 years. The majority of patients were educated at Junior high school level or below (68.7%) and were farmers or workers (68.1%). Clinical symptoms of CNS infectious disease mainly included fever, headache, signs of meningeal irritation, nausea and vomiting, which could be accompanied by consciousness disorder and focal neurological deficits. mNGS significantly improves the accuracy of clinical diagnosis. The rate of good prognosis of CNS infectious diseases was 97.5%, while the mortality rate was 0.3%.ConclusionsIn Chongqing area, the categories and species of CNS infectious pathogens are diverse, widely prevalent, and the clinical manifestations are complex. Moreover, the number of cases has been increasing in recent years. Understanding the epidemiological and clinical characteristics of CNS infectious diseases can help to recognize the regional differences, promote early accurate diagnosis and treatment, and improve prognosis.关键词：central nervous system;infection;epidemiology;clinical characteristics;Chongqing- 53
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发布时间：2024-06-24
Clinical Research
- “最新研究发现，枸杞多糖(LBP)能有效改善同型半胱氨酸(Hcy)诱导的小鼠肝细胞损伤。研究揭示了YAP1表达降低可能是Hcy诱导肝细胞损伤的关键过程，而LBP通过正向调节YAP1表达发挥保护作用。这一发现为治疗Hcy相关肝病提供了新的策略。”
摘要：ObjectiveTo investigate the effect and mechanism of lycium barbarum polysaccharide (LBP) on hepatocyte injury induced by homocysteine (Hcy).MethodsNormal 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.ResultsNCTC 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).ConclusionsThe 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.关键词：lycium barbarum polysaccharide;homocysteine;liver cell damage;DNA methylation- 47
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发布时间：2024-06-24 - “最新研究发现，五子衍宗丸能有效缓解帕金森病小鼠的运动功能障碍，保护多巴胺能神经元，其作用机制可能与调控Keap-1/Nrf2/HO-1通路抑制氧化应激反应有关。”
摘要：ObjectiveTo 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.MethodsTwenty-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.ResultsThe 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).ConclusionsWYP 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.关键词：Wuzi Yanzong Pill;Parkinson's disease;Keap-1/Nrf2/HO-1 pathway;neuron- 46
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发布时间：2024-06-24 -
Role of senescent genes in the treatment, prognosis and tumor microenvironment for osteosarcoma AI导读
“最新研究发现，ADH5、ARHGAP1、APOE、ATF4是成骨型骨肉瘤中潜在的衰老相关促癌或抑癌基因。基于这些基因构建的骨肉瘤衰老相关模型(OSRM)可判断骨肉瘤的治疗应答、预后和肿瘤微环境特征，为骨肉瘤的分子病理诊断和抗PD-1免疫治疗应答预测提供了新思路。”
摘要：ObjectiveTo analyze and verify the role of senescent genes in the treatment, prognosis, and tumor microenvironment (TME) characteristics of osteoblastic osteosarcoma, bioinformatic methods were employed.MethodsSenescent genes were obtained from the China National Genome Science database (https://ngdc.cncb.ac.cn/aging/index). The gene expression profile and clinical information of osteosarcoma patients were sourced from the TARGET database (https://ocg.cancer.gov/programs/target), while single-cell RNA-sequencing (scRNA-seq) data was collected from GSE162454 on the Gene Expression Omnibus (GEO) for downstream analysis. Osteosarcoma cells were classified based on scRNA-seq, and differential expression analysis between osteoblasts/chondroblasts and other cell types was conducted to identify differently expressed genes (DEGs). After matching with the senescent genes, prognostic senescent DEGs were identified through univariable and multivariable Cox regression analysis. Subsequently, the osteosarcoma senescent-related model (OSRM) was constructed, and the risk score was calculated. The role of OSRM in treatment, prognosis, and TME of osteosarcoma was further investigated.ResultsThe analysis revealed that GSE162454 contained 6 osteosarcoma samples, with 19 933 cells identified after filtering, quality control, and normalization. Seventeen cellular subtypes were identified using uniform manifold approximation and projection (UMAP) methods. A total of 4821 DEGs were found between osteoblasts/chondroblasts and other subtypes, with 132 senescent DEGs obtained after matching with the senescent gene set. In the TARGET database, 4 prognostic senescent DEGs [ADH5 (alcohol dehydrogenase 5), ARHGAP1 (Rho GTPase activating protein 1), APOE (apolipoprotein E), and ATF4 (activating transcription factor 4)] were identified through univariable and multivariable Cox analyses to construct OSRM. Based on risk score, patients were stratified into high- and low-risk groups, with the latter showing better prognosis (HR=0.13, 95%CI 0.06-0.28, P<0.001) and higher sensitivity to immune checkpoint inhibitors. qRT-PCR and Western blotting confirmed the high expression of senescent genes ADH5 (P<0.01), APOE (P<0.01), and ATF4 (P<0.05) in the K7M2 osteosarcoma cell line, suggesting the potential for predicting the response to anti-PD-1 immunotherapy for osteosarcoma.ConclusionsscRNA-seq facilitated the division of osteosarcoma into 17 cell subtypes. ADH5, ARHGAP1, APOE, and ATF4 emerged as potential cancer-promoting or suppressing senescent genes in osteosarcoma. OSRM was found to be associated with treatment response, prognosis, and TME characteristics, thereby promoting the molecular pathological diagnosis of osteoblastic osteosarcoma and prediction for anti-PD-1 immunotherapy.关键词：osteosarcoma;immune microenvironment;risk model;bioinformatic analysis- 34
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发布时间：2024-06-24 - “最新研究发现，β2肾上腺素受体(ADRB2)通过JNK/c-Jun通路调控前列腺癌细胞中铁死亡激活剂erastin诱导的铁死亡和自噬，为前列腺癌治疗提供新思路。”
摘要：ObjectiveTo investigate the effects and mechanism of β2 adrenergic receptors (ADRB2) in ferroptosis and autophagy induced by erastin (Era) in prostate cancer.MethodsPC-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).ResultsThe 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).ConclusionADRB2 regulated ferroptosis and autophagy induced by Era via JNK/c-Jun pathway in prostate cancer.关键词：prostate cancer;β2 adrenergic receptors;ferroptosis;autophagy- 34
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发布时间：2024-06-24
Basic Research
- “最新研究发现，补骨脂活性成分在骨质疏松症治疗中具有调节脂质代谢、骨代谢和氧化应激的作用，为预防和治疗提供新策略。”
摘要：Osteoporosis (OP) is a systemic bone disease characterized by low bone mass and damage to the microstructure of bone tissue, leading to increased bone fragility and susceptibility to fracture. Owing to its high prevalence, disability and mortality rates, as well as more sequelae, it brings heavy burden to patients and society. In recent years, as the research on the chemical and pharmacological effects of Psoralea corylifolia has made great progress, scholars have isolated compounds such as coumarins, flavonoids and monoterpene phenols, which have anti-OP, anti-oxidation, and anti-inflammatory properties, Psoralea corylifolia has been widely used in the treatment of OP. This article reviews the regulatory mechanism of active ingredients of Psoralea corylifolia in OP lipid metabolism, bone metabolism and oxidative stress, as well as related therapeutic strategies targeting Wnt/β-catenin, PI3K/Akt, PPAR-γ/Wnt, RANKL/RANK/MAPK and NF-κB signaling pathways, in order to provide further reference for the prevention and treatment of OP.关键词：Psoralea corylifolia;osteoporosis;oxidative stress;bone resorption;signal pathway- 48
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发布时间：2024-06-24 - “最新研究发现，维生素D在神经发育障碍性疾病中扮演重要角色，其缺乏可能影响大脑发育和神经递质平衡，为诊治提供新思路。”摘要：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.关键词：vitamin D;neuro-developmental disabilities;pathogenesis
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发布时间：2024-06-24 - “最新研究发现，维生素D在神经发育障碍性疾病中扮演重要角色，其缺乏可能影响大脑发育和神经递质平衡，为诊治提供新思路。”摘要：Inflammatory bowel disease (IBD) is a kind of immune disease. Although immune cells and related immunological reactions play a crucial role in the pathogenesis, non-immune cells of IBD, including intestinal epithelial cells, stromal cells, and endothelial cells are also involved in this process. Recent studies have shown that gut non-immune cells play an important role in the maintenance of intestinal epithelial homeostasis, matrix remodeling, immune response and inflammation. The composition, gene expression characteristics and cell functions of gut non-immune cells, as well as their role in the occurrence and progression of IBD, have been paid much attention in the field of gut research. In particular, recently, single-cell RNA sequencing (scRNA-seq) technology has initially clarified the gene expression characteristics and cell functions of different subgroups of intestinal cells, and the correlation between these changes and the occurrence and progression of IBD. Therefore, this review summarizes the progress of intestinal non-immune cells in IBD.关键词：inflammatory bowel disease;ulcerative colitis;Crohn's disease;single-cell RNA sequencing;epithelial cell;mesenchymal cell
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发布时间：2024-06-24 - “最新研究发现，肺类器官可有效模拟肺部免疫反应，为呼吸系统感染性疾病研究提供新视角。”
摘要：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.关键词：lung organoids;respiratory system;infectious diseases;stem cells;three-dimensional culture- 51
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发布时间：2024-06-24
Review
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