Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective: To investigate the association between edentulism and the risk of social isolation in middle-aged and elderly populations, provide empirical evidence for formulating social isolation prevention and intervention policies targeting edentulous middle-aged and elderly populations. Methods: Data were derived from the baseline survey (2011) and three follow-ups (2013, 2015, 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Participants were enrolled in the follow-up from the baseline. Those identified as socially isolated in any of the follow-up surveys conducted in 2013, 2015, or 2018 were considered to have reached the endpoint; otherwise, the follow-up was continued until the end of the 2018 survey; 9 870 individuals were ultimately included. Subjects were grouped by edentulism status. Chi-square test and multivariate Cox regression analysis were performed using Stata 17.0. Results: During a median follow-up of 6.54 years, 1 800 cases of social isolation occurred, with an incidence rate of 18.23%（17.47%~18.99%）. Multivariate Cox regression showed that edentulism was associated with an increased risk of social isolation (HR=1.21, 95% CI: 1.03-1.42) after adjusting for confounders. Subgroup analysis revealed population heterogeneity. Sensitivity analyses confirmed the stability of the results. Conclusion Edentulism is associated with an increased risk of social isolation in middle-aged and elderly adults.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

With the advance of the economy and population aging, the acceleration of urbanization and the change of people's lifestyles, the prevalence of chronic diseases has become very serious. However, the etiologies and pathogeneses of the diseases are not yet clear, and the evidence of effective prevention and treatment strategies is lacking. Cohort study is an important method for exploring etiology and pathogenesis. Therefore, based on the support of the Ministry of Science and Technology for precision medicine in 2016, we launched a prospective cohort study of common chronic and non-communicable diseases in three provinces (Hubei, Hunan and Henan) in central China. Three independent and integratable sub-cohorts consisting of 115 424 participants at baseline survey and 107 252 participants in follow up were established, including dynamic measurements in 39 000 subjects in Dongfeng-Tongji prospective cohort. Each participant was asked to complete a questionnaire survey, an anthropometric measurement, a laboratory measurement, and blood and urine samples were collected from them. The cohort study contributes greatly to elucidating the etiologies and pathogeneses of common chronic and non-communicable disease in Chinese population and the development of precision medicine in China. This paper briefly introduces the design concept, basic information, major achievements and progress, and challenges of the prospective cohort study of common chronic and non-communicable diseases in central China.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

To meet the requirement of pathological practice and development, we systematically analyzed the situation of pathological residents training and the importance of initiating the clinical scientific research training. Additionally, we proposed the principle and implementation strategy for clinical scientific research training. According to features of pathological practice, we employed the modularized teaching to divide the training courses into several modules: discussion module for clinical pathology, lecture module for advanced research, and training modules for basic scientific theory, technology and writing skill. With these approaches, the systematic and structured system of standardized residents training is implemented to improve the clinical research ability of pathological residents.

Objective: To establish the quality standard for Jiuwei Zhaxun pills. Methods: Fructus Chebulae, Flos Carthami and Herba Dracocephali Heterophylli were identified by TLC. HPLC was used to determine the content of gallic acid in Jiuwei Zhaxun pills. Results: TLC showed clear sports without any interference from the negative control. Gallic acid showed a good linear relationship (r=0. 999 7) within the range of 0. 028 6-0. 572 0 μg. The average recovery was 97. 74% with the RSD of 0. 95% (n=6). Conclusion:The methods are with strong specificity, high sensitivity and good reproducibility, which can be applied in the quality control of Jiuwei Zhaxun pills.

Objective To investigate the risks and benefits of interventions promoting placental transfusion (PT) at delivery [delayed cord clamping (DCC) or umbilical cord milking (UCM)] compared with early cord clamping (ECC) on outcomes among very low birth weight infants (VLBWI).Methods A systematic search was conducted of PubMed, EMBASE, ClinicalTrials.gov, China Academic Journal Network Publishing Database and Wanfang Medical Databases (January 1965 to July 2014) for randomized controlled trial (RCT) articles relating to PT strategies (DCC and UCM) in VLBWI.The Cochrane Handbook 5.1.0 was used to evaluate the methodological quality and RevMan 5.3 software from Cochrane Collaboration was used for metaanalysis.The fixed effect or random effect model was adopted according to the result of heterogeneity, Results We identified 14 eligible studies describing a total of 659 neonates with an average birth weight ＜ 1 500 g.There were eight studies for DCC and six studies for UCM.Compared with the control, benefits of greater PT decreased any grade intraventricular hemorrhage (IVH) (nine studies, OR=0.49, 95％CI: 0.32-0.77, P ＜ 0.01), increased the blood pressure at four hours of life (eight studies, MD=4.42, 95％CI: 3.85-4.98, P ＜ 0.01), and also showed higher initial hemoglobin (Hb) level (six studies, MD=3.52, 95％CI: 1.67-5.37, P ＜ 0.01) and lower incidence of sepsis during the hospital stay (five studies, OR=0.46, 95％CI: 0.26-0.83, P=0.01).No differences were observed between the groups about the fllowing indicators (all P ＞ 0.05): 5-minute Apgar scores (MD=0.01,95％CI:-0.21-0.22), admission temperature (MD=0.13, 95％CI:-0.15 to 0.41), peak serum bilirubin levels (MD=0.59, 95％CI:-0.13 to 1.31), initial reported hematocrit (MD=3.48, 95％CI:-0.46 to 7.43), mortality before discharge (OR=0.63, 95％CI:0.31-1.25), Bell's stage 2 or greater necrotizing enterocolitis (OR=0.62 ,95％CI: 0.29-1.33), rates of transfusion due to anemia (OR=0.63, 95％CI: 0.35-1.15) and oxygen therapy at 36 weeks of corrected age (OR=0.79, 95％CI: 0.46-1.34).Conclusions It is suggested that enhanced PT (both DCC and UCM) at birth is safe and provide better neonatal outcomes than ECC for those VLBWI, most notably reduces the overall IVH occurrence and lower the incidence of sepsis.The optimal umbilical cord clamping practice and UCM among VLBWI infants remains uncertain and long-term neurodevelopmental outcomes are warranted.

Objective To investigate the expression of p73 gene and its protein and their relation with clinicopathologic features in nasopharyngeal carcinoma (NPC) tissues.Methods Expression of p73 mRNA and protein in 52 NPC and 25 normal nasopharyngeal tissues was detected by real-time fluorescent quantitative PCR and immunohistochemistry.Results Expression of p73 mRNA and protein was significantly higher in NPC than that in normal nasopharyngeal tissues (mRNA:73.1％ vs 24.0 ％,protein:71.2 ％ vs 36.0 ％),there were significant statistical differences between the two groups (P ＜ 0.05),and their expression was closely related to tumor invasion depth,degree of differentiation and clinical stage (P ＜ 0.05).Expression of p73 gene and protein was not closely related to age and gender (P ＞ 0.05).Conclusion Detection expression of p73 mRNA and its protein can be helpful in the diagnosis and prognostic evaluation in NPC.

Objective To evaluate the clinical efficacy,overall survival and toxicities in the patients with advanced non-small cell lung cancer treated by liposome paclitaxel combined with nedaplatin as first-line treating.Methods 34 cases with advanced NSCLC were treated with liposome paclitaxel 150 mg/m2 on day 1 and nedaplatin 80 mg/m2 on day 1 by intravenous infusion,with 21 days as one cycle.The patients were treated with chemotherapy more than 2 cycles.Efficacy evaluation and adverse events were evaluated every 2 cycles.Results 34 patients were available for evaluation of efficacy and adverse events.The patients recieved 174 cycles of chemotherapy,and the median was 5.3 cycles.The objective response rate of liposome paclitaxel combined with nedaplatin was 32.3 ％,the disease control rate was 67.6 ％,the median overall survival was 9.5 months (95 ％ CI 6.2-10.7),1 years survival rate was 40.6 ％.The main adverse events were hematological and gastrointestinal toxicities.Frequent grade Ⅲ-Ⅳ toxicities included neutropenia (41.7 ％),anemia (17.6 ％),thrombocytopenia (8.8 ％),nausea and vomiting (8.8 ％),diarrhea (5.8 ％).Conclusions The regimen of liposome paclitaxel combined with nedaplatin is against advanced non-small cell lung cancer with high efficacy and acceptable toxicities,and it may be used as a new choice for treatment of advanced non-small cell lung cancer.