Objective To investigate the effect and mechanism of miR-195-5p on myocardial fibro-sis in rats with atrial fibrillation(AF).Methods A total of 72 male SD rats were randomly divid-ed into control group,AF group,negative control group,miR-195-5p inhibitor group,recombinant adeno-associated virus serotype 9(rAAV9)group(miR-195-5p inhibitor+rAAV9-negative con-trol),and combination group[miR-195-5p inhibitor+rAAV9-siRNA-SMAD homolog 7(Smad)],with 12 rats in each group.Except for the control group,the rats in the other groups were inflicted to construct AF model.After receiving corresponding intervention measures,elec-trocardiography was conducted to record the incidence and the duration of AF.HE staining and Masson staining were used to observe the pathological changes and fibrosis in the myocardial tis-sues,respectively.qRT-PCR was applied to detect the mRNA levels of miR-195-5p and Smad7,and Western blotting was performed to detect the expression of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,Collagen-Ⅰ and Collagen-Ⅲ in the myocardial tissues.Dual luciferase assay was used to verify the regulatory effect of miR-195-5p on Smad7.Results Compared with the control group,the AF group had significantly higher AF incidence(75.0％vs 0)and longer duration(27.02±2.65 s vs 0 s),larger collagen volume fraction(CVF)[(14.47±0.89)％vs(2.12±0.35)％],and increased expression levels of miR-195-5p(3.27±0.21 vs 1.00±0.10),TGF-β1(0.76±0.08 vs 0.23±0.04),Collagen-Ⅰ(0.58±0.07 vs 0.20±0.04),Collagen-Ⅲ(0.46±0.05 vs 0.11±0.02),p-Smad2/Smad2(0.92±0.10 vs 0.37±0.05),and p-Smad3/Smad3(0.65±0.06 vs 0.14±0.03),but notably decreased expression of Smad7 at mRNA(0.32±0.06 vs 1.02±0.09)and protein(0.19±0.03 vs 0.58±0.07)levels in the myocardial tissues(P＜0.05).The AF incidence and duration,CVF,miR-195-5p level,and protein levels of TGF-β1,Collagen-Ⅰ,Colla-gen-Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 were significantly decreased,and the mRNA and protein levels of Smad7 were significantly increased in the miR-195-5p inhibitor group than the AF group and the negative control group(P＜0.05).The combined treatment increased the inci-dence and duration of AF,CVF,myocardial TGF-β1,Collagen-Ⅰ,Collagen-Ⅲ,p-Smad2/Smad2 and p-Smad3/Smad3 expression levels,and decreased the mRNA and protein expressions of Smad7 when compared with the miR-195-5p inhibitor group and the rAAV9 group(P＜0.05).Conclusion Down-regulation of miR-195-5p alleviates myocardial fibrosis in AF rats probably by targeting Smad7 to inhibit TGF-β1 signaling.

Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C＞T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

Objective To assess the validity and utility of the four-column concept by comparing the imaging results and clinical efficacy of the four-column concept with the Schatzker typing concept in the treatment of type Ⅰ-Ⅳ tibial plateau fractures.Methods A total of 70 tibial plateau fracture patients selected from Dongguan Hospital,Guangzhou University of Traditional Chinese Medicine from September 1,2022 to April 30,2023,who were divided into treatment group and control group,with 35 patients in each group.All patients underwent complete X-ray and CT three-dimensional reconstruction examination,and regular postoperative review of orthopantomograms of the knee was performed.Data were collected at 1 month and 1 year postoperatively,including measurements of posterior tibial slope(PTSA),tibial plateau anterior(TPA),and secondary displacement of the articular surfaces,as well as the visual analogue scale(VAS),range of motion(ROM),and Lysholm knee score scale(LKSS).Results The operation duration and bleeding volume in treatment group were less than that in control group,and the difference were statistically significant(P＜0.05).There were significant differentes at 1 month after postoperatively in knee ROM and Lysholm scores between two groups(P＜0.05).There were significant differences in PTSA and articular surface collapse at 1 month and 1 year postoperatively(P＜0.05).Conclusion Surgical treatment of Schatzker type Ⅰ-Ⅳ tibial plateau fracture under the guidance of the four-column concept can effectively restore the alignment of fracture ends and fixation strength,and improve the mobility of the knee joint,which is worthy of popularization and application in the clinic.

Objective:To explore the clinical features, genetic traits and prognosis status of acute myeloid leukemia (AML) patients with TP53 mutation.Methods:A retrospective case series study was performed. Clinical data of 42 AML patients with TP53 mutation abundance of at least 10% who were admitted to the First Hospital of Jilin University from April 2018 to August 2023 were collected. Chromosomal karyotypes were detected using fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) was performed on bone marrow samples from these patients. The Kaplan-Meier method was utilized to analyze the recurrence-free survival (RFS) of 22 patients who achieved complete remission (CR) after induction therapy, as well as the overall survival (OS) of 39 patients who underwent treatment. The Cox proportional hazards model was employed to analyze the factors influencing RFS and OS. Thirty-one patients who underwent induction therapy for ≥ 2 courses were divided into the non-refractory group (22 cases) and the refractory group (9 cases) based on whether CR was achieved after induction therapy, and the clinical and genetic characteristics and prognosis of the two groups were compared.Results:Among the 42 AML patients with TP53 mutation, there were 26 males and 16 females, with a median age [ M( Q1, Q3)] of 57.0 (44.0, 63.5) years. At the initial stage, the median white blood cell count in peripheral blood was 4.06×10 9/L (2.59×10 9/L, 27.36×10 9/L), the median proportion of bone marrow primitive cells was 45.25% (29.00%, 80.63%), the proportion of primitive and immature cells in bone marrow cell immune analysis was 28.70% (12.71%, 61.48%), and the median TP53 mutation abundance was 55.48% (38.72%, 73.31%). Among the 42 patients, 23 cases (54.76%) had complex chromosomal karyotypes, with the most frequent abnormal chromosomes being chromosome 5 (47.62%, 20 cases), chromosome 7 (45.24%, 19 cases) and chromosome 17 (26.19%, 10 cases). The mutant genes with high mutation frequency were DNMT3A (19.05%, 8 cases), N/KRAS (19.05%, 8 cases), ASXL1 (16.67%, 7 cases) and NPM1 (16.67%, 7 cases). Among the 39 patients with detailed TP53 mutation data, 36 had missense mutations and 3 had frameshift mutations. In the non-refractory and refractory groups, the N/KRAS mutation rates were 13.6% (3/22) and 55.6% (5/9), respectively ( P = 0.027). The median RFS time of 22 CR patients after induction therapy was 109 d (95% CI: 57-483 d). The results of multivariate Cox regression analysis showed that complex chromosomal karyotype was an independent risk factor for RFS ( HR = 11.819, 95% CI: 1.345-103.880, P = 0.028). The median RFS time of patients without and with complex chromosomal karyotypes was 842 d (95% CI: 0-1 716 d) and 148 d (95% CI: 88-208 d), respectively, and the difference in RFS between the two groups was statistically significant ( P = 0.001). The median OS time of 39 patients receiving treatment was 151 d (95% CI: 75-227 d). The results of multivariate Cox regression analysis showed that NPM1 gene mutation was an independent protective factor for OS ( HR = 0.289, 95% CI: 0.075-1.114, P = 0.071). The median OS time of patients with and without NPM1 gene mutation was 1 562 d (95% CI: 610- 1 710 d) and 136 d (95% CI: 99-173 d), respectively, and the difference in OS between the two groups was statistically significant ( P = 0.020). Conclusions:TP53-mutant AML patients often have poor chromosomal karyotypes and genetic abnormalities, while refractory AML patients often have N/KRAS mutation. The complex chromosomal karyotype is a risk factor for RFS, while NPM1 gene mutation is a protective factor for OS.

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

Objective:To explore the mechanism of Xuanfei Dahe Decoction in treating asthmatic mice through network pharmacology and animal experiments.Methods:The active components and their targets of Xuanfei Dahe Decoction were retrieved from TCMSP, and the asthma targets were obtained by searching the GeneCards, DisGeNet, OMIM, TTD and DrugBank databases. PPI network of intersection targets was constructed using string database and Cytoscape 3.9.0 software. Go function and KEGG pathway enrichment were analyzed by metascape database. The mice were divided into a blank group of 6 mice and a model group of 30 mice according to the random number table method. The asthma model was prepared in the model group. Totally 30 successfully modeled mice were divided into the model group, the dexamethasone group, and Xuanfei Dahe Decoction low-, medium- and high-dosage groups according to the random number table method, with 6 mice in each group. On the 5th day, gavage was initiated. Xuanfei Dahe Decoction low-, medium- and high-dosage groups were respectively gavaged with Xuanfei Dahe Decoction liquid at concentrations of 6.84, 13.68 and 27.36 g/kg. The dexamethasone group was gavaged with dexamethasone acetate tablets at concentrations of 2.73 mg/kg. The blank group and the model group were gavaged with the same volume of sterile normal saline once a day for 14 consecutive days. The pathological changes of lung tissue were observed by HE staining, the level of serum IL-17 was detected by ELISA, and the expression of IL-17 in lung tissue was detected by immunohistochemistry.Results:120 asthma targets and 13 key targets were obtained from Xuanfei Dahe Decoction. Pathway enrichment analysis suggested that IL-17 signaling pathway was one of the key pathways. Compared with the model group, the levels of IL-17 in the serum of the low-dose, medium-dose and high-dose Xuanfei Dahe Decoction groups and the expression of IL-17A in the lung tissue of the medium-dose Xuanfei Dahe Decoction group decreased ( P<0.05). Conclusion:Xuanfei Dahe Decoction may treat asthma by restrain airway inflammation mediated by Th17/IL-17.

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C＞T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.