Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
Male ; Female ; Humans ; Child ; Stroke Volume ; Retrospective Studies ; Ventricular Function, Left ; Phenotype ; Cardiomyopathy, Dilated/diagnosis* ; Mutation ; ATPases Associated with Diverse Cellular Activities/genetics* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

OBJECTIVE: No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population. METHODS: A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking. RESULTS: Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively. CONCLUSION The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.
Male ; Humans ; Female ; Smoking/epidemiology* ; Smoking Cessation ; Smokers ; Risk ; Lung Neoplasms/etiology* ; Risk Factors

Humans ; Nutrition Surveys ; Diabetes Mellitus, Type 2/chemically induced* ; Environmental Exposure/analysis* ; Environmental Monitoring ; Phthalic Acids/toxicity* ; Environmental Pollutants/toxicity*

OBJECTIVE: To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population. METHODS: We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort). RESULTS: In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women. CONCLUSION The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.
Child ; Female ; Humans ; Asthma/epidemiology* ; Breast Neoplasms ; East Asian People ; Lung Neoplasms/etiology* ; Tobacco Smoke Pollution/adverse effects* ; China

Asian People ; Case-Control Studies ; China/epidemiology* ; Humans ; Risk Factors ; Tobacco

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ² test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ² test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ²=6.971, P=0.008) and nCRT group (6.9% (2/29), χ²=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ²=10.881, P=0.001; χ²=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ²=6.740, P=0.009) and nCRT group (31.0% (9/29), χ²=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ²=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ²=4.976, P=0.083) and progression-free survival (χ²=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.
Adenocarcinoma/pathology* ; Adult ; Aged ; Cohort Studies ; Esophagogastric Junction/pathology* ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Propensity Score

OBJECTIVE: To investigate the clinical efficacy and prognosis of patients with multiple myeloma (MM) treated by long-term maintenance lenalidomide treatment. METHODS: A total of 97 patients diagnosed as MM in the Department of Hematology of First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2012 to 2019 were selected, and the basic clinical characteristics and laboratory indicators of the patients were tested and evaluated. After long-term maintenance lenalidomide treatment for patients with MM, the short-term and long-term clinical efficacy and the incidence of adverse reactions were evaluated, and factors affecting the prognosis of the patients were analyzed. RESULTS: Before maintenance treatment, 47.42% of the patients (46/97) did not achieve complete remission (CR), among 52.58% (51/97) of CR patients, there were 20.62% of the patients showed minimal residual leukemia (MRD) negative. After lenalidomide maintenance treatment, the patients who did not achieve CR were reduced to 24.74% (24/97), among 75.26% (73/97) of the patients with CR, there were 47.42% of the patients showed MRD negative, the difference showed statistically significant (P<0.001). After maintenance treatment, the median pro-gression-free survival of the patients was 58 months, and the 5-year survival rate was 89.69%. The incidence of adverse reactions was 40.21% (39/97), including neutropenia (31/39, 79.49%), fatigue (21/39, 53.85%), thrombocytopenia (17/39, 43.59%) and gastrointestinal reaction (15/39, 38.46%) were the most common. The discontinuation rate was 24.74% (24/97), and the median time for discontinuation was 21 months. The main reasons for discontinuation were neutropenia (12/24, 50.00%) , thrombocytopenia (8/24, 33.33%) and gastrointestinal reactions accounted for 8.33% (2/24). Old age and positive MRD were the risk factors affecting the prognosis of the patients. The adjusted OR was 1.43 (95% CI 1.03-1.76, P=0.034) and 3.78 (95% CI 2.56-9.56, P=0.037), respectively. CONCLUSION The long-term maintenance lenalidomide treatment shows a good clinical effect on patients with MM, and MRD detection can assist the cilinical judge the prognosis of the patients. During maintenance treatment, the clinical symptoms, especially blood system damage of the patients should be take care, so as to avoid serious adverse reactions.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Humans ; Lenalidomide/therapeutic use* ; Multiple Myeloma/drug therapy* ; Prognosis ; Treatment Outcome

OBJECTIVE: To study the prevalence and influencing factors of metabolic syndrome(MS) in male occupational population in the mineral industry. METHODS: A total of 2 654 male employees in the mining area of a mining group in Xingtai City were selected as the study subjects using the convenient sampling method. The general demographic data, behavior and lifestyle, work status, and biochemical examination results of the study subjects were collected, and the influencing factors of MS were analyzed by multi-factor logistic regression. RESULTS: The detection rate of MS was 16.0%(425/2 654) in these 2 654 male workers. The detection rate of MS increased with age and length of service(all P<0.05). The detection rate of MS in male workers with hypertension, high blood sugar, central obesity, high triglyceride and low high-density lipoprotein was higher than that in control workers(all P<0.01). The results of multivariate logistic regression analysis showed that age, work shifts, salt intake, dietary habit, alcohol drinking, sleep time, physical exercise, and body mass index were all influencing factors for MS(all P<0.05). CONCLUSION: Male workers have a high incidence of MS. Older age, shift work, high-salt diet, meat-based diet, alcohol drinking, severely insufficient sleep time, and overweight/obesity increase the risk of MS in male workers.