BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective:To analyze the clinicopathological factors affecting the prognosis of patients after curative resection of lung metastases (LMs) from colorectal cancer (CRC) and to construct a clinical risk scoring (CRS) model.Methods:This study retrospectively collected clinicopathological data and follow-up information on 132 patients who underwent radical resection of LMs from CRC at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2010 and December 2020. We analyzed the clinicopathological factors influencing patient prognosis using univariate and multivariate Cox proportional hazards regression models, and we developed a risk stratification model for prognostic prediction.Results:The median follow-up duration for the cohort of 132 patients was 54.2 months. During this period, 61 patients (46.2%) experienced recurrence or distant metastasis, resulting in a 5-year DFS rate of 54.1%. Additionally, 33 patients (25.0%) died, corresponding to a 5-year overall survival (OS) rate of 76.7%. Univariate Cox proportional hazards regression model analysis indicated that ten clinicopathological factors were significantly associated with OS (all P＜0.05). These factors include the total number of lymph nodes (LNs) dissected from the primary tumor (PT) <16, the number of negative LNs from the PT <13, pN(+) of the PT, logarithmic odds of positive lymph nodes (LODDS) of the PT ≥-1.1, lymph nodes ratio (LNR) of the PT ≥0.02, preoperative carcinoembryonic antigen (CEA) level before LMs resection ≥10 ng/ml, the presence of hilar/mediastinal LN metastasis, the number of LMs ≥2, the maximum diameter of LMs ≥2.5 cm, and the necessity for hilar/mediastinal lymphadenectomy. Multivariate Cox proportional hazards regression analysis identified the number of negative LNs <13 ( HR=3.01, 95% CI: 1.28-7.03, P=0.011), pN(+) of the PT ( HR=5.04, 95% CI: 1.51-16.84, P=0.009), preoperative CEA level before LMs resection ≥10 ng/ml ( HR=5.39, 95% CI: 1.80-16.19, P=0.003), the number of LMs ≥2 ( HR=2.47, 95% CI: 1.09-5.60, P=0.030), and the necessity for hilar/mediastinal lymphadenectomy ( HR=2.74, 95% CI: 1.15-6.52, P=0.023) as independent prognostic risk factors. Patients were categorized based on independent risk factors, revealing statistically significant differences in OS across the groups with CRS scores of ≤2, 3～4, and ≥5 ( P＜0.001). Conclusions:Independent risk factors associated with LMs from CRC patients include the number of negative LNs <13, pN(+) of the PT, preoperative CEA level before LMs resection ≥10 ng/ml, the number of LMs ≥2, and the necessity for hilar/mediastinal lymphadenectomy. Patients scoring 3 or higher on the CRS model may warrant cautious assessment for the appropriateness of direct surgical treatment.

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

Objective To investigate the protective effects of Wuling capsule on mice with autoimmune hepatitis(AIH).Methods Mice were randomly divided into control group,AIH model group,Wuling capsule low-dose group(0.5 g·kg-1·d-1),Wuling capsule middle-dose group(1.0 g·kg-1·d-1),and Wuling capsule high-dose group(2.0 g·kg-1·d-1),with 10 mice in each group.The Wuling capsule groups were administered with Wuling capsule suspension of different doses orally at a volume of 10 mL/kg once daily;the control group and AIH model group were given the same volume of saline by gavage.After 14 d of administration,mice in the AIH model group and Wuling capsule groups were injected with concanavalin A(20 mg/kg)via the tail vein,and the serum,liver,and spleen were collected 8 h after injection.Serum alanine transaminase(ALT)and aspartate transaminase(AST)levels were measured using an automatic biochemical analyzer;hematoxylin-eosin staining was used to observe the pathological structure of the liver tissue;the contents of interleukin(IL)-6,IL-4,and tumor necrosis factor(TNF)-α in liver were determined by enzyme-linked immunosorbent assay,and quantitative polymerase chain reaction was used to determine the relative mRNA expression levels of IL-6,IL-4,TNF-α,Toll-like receptor 4(TLR4),and nuclear factor κB(NF-κB)in the liver.Fluorescence immunoassay was used to analyze the expression and nuclear translocation of NF-κB p65 protein in the liver.Results Compared with the control group,the AIH model group showed abnormal liver morphology and structure,increased serum ALT and AST levels,increased contents of IL-4,IL-6,and TNF-α in the liver,upregulated mRNA expression levels of IL-6,IL-4,TNF-α,TLR4,and NF-κB in the liver,and increased nuclear entry of NF-κB p65.Wuling capsule significantly improved the pathological structure of the liver in AIH mice,reduced serum ALT and AST levels,decreased the contents of IL-4,IL-6,and TNF-α in the liver and the mRNA expression levels of TLR4,NF-κB,IL-4,IL-6,and inhibited the nuclear activation of NF-κB p65.Conclusion Wuling capsule has significant protective effects on AIH mice,which may be related to the TLR4/NF-κB signaling pathway.

Objective:To construct and validate a prognostic prediction model for patients with ovarian metastases from colorectal cancer after radical resection.Methods:A retrospective case series analysis was conducted on the clinical and pathological data of 81 patients with colorectal cancer and ovarian metastases who underwent radical resection for ovarian metastases at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, between January 2014 and December 2023. The patients were all female, with an age ( M(IQR)) of 49(13) years (range: 22 to 79 years). The primary tumor was located in the colon in 60 cases (74.1%) and in the rectum in 21 cases (25.9%). Univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting prognosis. A risk scoring system was constructed, and patients were assigned to high-risk and low-risk groups based on their risk scores. The predictive performance of the scoring system was assessed, and 5-fold cross-validation was performed to evaluate the model′s stability on the internal dataset. Results:Among the 81 patients with ovarian metastases, a high proportion had T4 stage (58 cases, 71.6%), lymph node positivity (68 cases, 84.0%), and colon cancer (60 cases, 74.1%). Preoperative imaging suggested unilateral ovarian metastasis in 15 patients (23.4%), but pathological examination after bilateral oophorectomy confirmed bilateral ovarian metastases. Among the 17 patients who initially underwent unilateral oophorectomy, 11 developed contralateral ovarian metastases at varying times postoperatively. Univariate Cox proportional hazards regression analysis revealed that positive lymph node ratio ( HR=2.68,95% CI:1.41 to 5.09, P=0.003), N stage ( HR=2.07,95% CI:1.08 to 3.95, P=0.028),maximum diameter of metastatic tumors ( HR=2.27,95% CI:1.04 to 4.96, P=0.040),and peritoneal metastasis or ascites at the time of ovarian metastasis ( HR=2.04,95% CI:1.02 to 4.08, P=0.043) were significantly associated with overall survival in patients with ovarian metastasis from colorectal cancer. Multivariate regression analysis identified that positive lymph node ratio ( HR=3.34,95% CI:1.08 to 10.34, P=0.037) and maximum diameter of metastatic tumors ( HR=2.65,95% CI:1.19 to 5.88, P=0.017) were independent prognostic factors for overall survival following radical oophorectomy in patients with ovarian metastasis from colorectal cancer. Based on the regression coefficients from the multivariate analysis for variables (ovarian metastatic tumor diameter ≥6 cm, positive lymph node ratio ≥0.3,and presence of peritoneal metastasis or ascites), a risk scoring system was developed. Using the optimal cutoff value (154 points) for the risk score,patients were divided into high-risk (19 cases) and low-risk (62 cases) groups. Kaplan-Meier survival curves demonstrated that the high-risk group had significantly lower median overall survival (27 months) and median disease-free survival (22 months) compared to the low-risk group (median overall survival 90 months,median disease-free survival not reached; both P<0.01). Receiver operating characteristic curve analysis showed that the area under the curve(AUC) for predicting 1-,3-,and 5-year overall survival was 0.731(95% CI:0.563 to 0.899), 0.703(95% CI:0.573 to 0.833), and 0.776(95% CI: 0.657 to 0.894), respectively. The AUC for predicting 1-,3-, and 5-year disease-free survival was 0.724(95% CI:0.397 to 0.993),0.710(95% CI:0.514 to 0.906),and 0.688(95% CI:0.478 to 0.898),respectively,indicating good performance of the model.The decision curve analysis showed that the model has good clinical net benefit and the results of the 5-fold cross-validation showed that the model demonstrated stability in the internal dataset. Conclusions:When performing radical resection for ovarian metastasis from colorectal cancer,bilateral oophorectomy should be considered to minimize the risk of postoperative recurrence. Patients with ovarian metastasis from colorectal cancer,characterized by a metastatic tumor diameter ≥6 cm,a positive lymph node ratio ≥0.3,and the presence of peritoneal metastasis or ascites, tend to have a poorer prognosis. Based on these findings,a clinical prognostic scoring system for radical resection of ovarian metastasis from colorectal cancer has been developed to stratify patients into different risk groups and may assist in postoperative risk assessment and management.

Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.

Objective:To analyze the clinicopathological factors affecting the prognosis of patients after curative resection of lung metastases (LMs) from colorectal cancer (CRC) and to construct a clinical risk scoring (CRS) model.Methods:This study retrospectively collected clinicopathological data and follow-up information on 132 patients who underwent radical resection of LMs from CRC at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2010 and December 2020. We analyzed the clinicopathological factors influencing patient prognosis using univariate and multivariate Cox proportional hazards regression models, and we developed a risk stratification model for prognostic prediction.Results:The median follow-up duration for the cohort of 132 patients was 54.2 months. During this period, 61 patients (46.2%) experienced recurrence or distant metastasis, resulting in a 5-year DFS rate of 54.1%. Additionally, 33 patients (25.0%) died, corresponding to a 5-year overall survival (OS) rate of 76.7%. Univariate Cox proportional hazards regression model analysis indicated that ten clinicopathological factors were significantly associated with OS (all P＜0.05). These factors include the total number of lymph nodes (LNs) dissected from the primary tumor (PT) <16, the number of negative LNs from the PT <13, pN(+) of the PT, logarithmic odds of positive lymph nodes (LODDS) of the PT ≥-1.1, lymph nodes ratio (LNR) of the PT ≥0.02, preoperative carcinoembryonic antigen (CEA) level before LMs resection ≥10 ng/ml, the presence of hilar/mediastinal LN metastasis, the number of LMs ≥2, the maximum diameter of LMs ≥2.5 cm, and the necessity for hilar/mediastinal lymphadenectomy. Multivariate Cox proportional hazards regression analysis identified the number of negative LNs <13 ( HR=3.01, 95% CI: 1.28-7.03, P=0.011), pN(+) of the PT ( HR=5.04, 95% CI: 1.51-16.84, P=0.009), preoperative CEA level before LMs resection ≥10 ng/ml ( HR=5.39, 95% CI: 1.80-16.19, P=0.003), the number of LMs ≥2 ( HR=2.47, 95% CI: 1.09-5.60, P=0.030), and the necessity for hilar/mediastinal lymphadenectomy ( HR=2.74, 95% CI: 1.15-6.52, P=0.023) as independent prognostic risk factors. Patients were categorized based on independent risk factors, revealing statistically significant differences in OS across the groups with CRS scores of ≤2, 3～4, and ≥5 ( P＜0.001). Conclusions:Independent risk factors associated with LMs from CRC patients include the number of negative LNs <13, pN(+) of the PT, preoperative CEA level before LMs resection ≥10 ng/ml, the number of LMs ≥2, and the necessity for hilar/mediastinal lymphadenectomy. Patients scoring 3 or higher on the CRS model may warrant cautious assessment for the appropriateness of direct surgical treatment.

Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.