The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective To investigate the distribution of pathogens and change of homology of Acinetobacter bau-mannii(AB)in intensive care units(ICUs)of partial medical institutions in Shanghai before and after the pandemic of coronavirus disease 2019(COVID-19).Methods Pathogens were isolated and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),the whole genome of AB was sequenced using Illumina Miseq sequencing platform,and its genetic relationship was explored based on multilocus sequence typing(MLST)and core genome multilocus sequence typing(cgMLST).Results The total detection rate of patho-gens in ICU environment after the pandemic was lower than before the pandemic([6.10％,101/1 656]vs[10.77％,181/1 680];P＜0.05).Before and after the pandemic,the proportion of AB detected on the surface of bedding in the ICU environment remained at the highest level.After the pandemic,the ST types showed a diverse distribution.MLST_Pasteur results showed that 162 strains of AB were divided into 20 ST types,with ST2(80.25％,n=130)being the main type.MLST_Oxford results showed that there were 19 ST types among 162 strains,with ST208(37.04％,n=60)being the main type.The clustering analysis based on cgMLST showed that ST208_Oxford had closer genetic relationship with ST540_Oxford and ST369_Oxford after the pandemic.ST164_Pasteur clone changed from ST234_Oxford before the pandemic to ST1418_Oxford after the pandemic,and 2 new types of ST_Pasteurr and 11 new types of ST_Oxford were discovered.Conclusion The detection rate of pathogens from ICU environment after the pandemic is lower than before the pandemic,and the distribution of ST types is slightly different at the same detection sites before and after the pandemic.ST2_Pasteur/ST208_Oxford is still the dominant epidemic clone before and after the pandemic,but some alleles have changed.cgMLST is more accurate than MLST_Oxford and MLST_Pasteur in homology analysis,evolution,spread,and outbreak analysis.

AIM: To investigate the effect of repeated intravitreal injection of anti-vascular endothelial growth factor(VEGF)on the vitreomacular interface(VMI)and its related risk factors in patients with diabetic macular edema(DME).METHODS: The clinical data of 31 patients(55 eyes)with DME who received intravitreal injections of Conbercept(3+PRN)in the ophthalmology department of the First People's Hospital of Zunyi from January 2018 to December 2021 were analyzed retrospectively. There were 9 cases(13 eyes)in the group that has changes in VMI and 22 cases(42 eyes)in the other group that has no changes in VMI. The best corrected visual acuity(BCVA), central retinal thickness(CRT), and central choroidal thickness(CCT)of the two groups were compared, and the risk factors of VMI change were analyzed.RESULTS: The patients were followed up for an average of 9.58±8.32mo, received an average of 4.07±2.17 times of anti-VEGF therapy, and the number of intravitreal injections in VMI changed group was more than that in VMI unchanged group(5.77±2.09 times vs. 3.55±1.93 times, P=0.001). At the last follow-up, compared with before treatment, the BCVA of both patients improved significantly after treatment(both P<0.05), while CCT had no significant change(both P>0.05). CRT of patients in the VMI unchanged group decreased significantly(P=0.039), but there was no significant change in patients of VMI changed group(P=0.627). Logistic regression analysis showed that BCVA was a risk factor for VMI change before treatment(P=0.049, OR=6.210, 95%CI 1.006～38.346).CONCLUSIONS: The VMI of DME patients may change during repeated intravitreal injections of anti-VEGF drugs. The worse the BCVA before treatment, the higher the risk of change in VMI, and the patients with VMI change have a poor response to anti-VEGF treatment.

Humans ; Cohort Studies ; Body Mass Index ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Inflammation ; Treatment Outcome ; Risk Factors

BACKGROUND: There are few data comparing clinical outcomes of complex percutaneous coronary intervention (CPCI) when using biodegradable polymer drug-eluting stents (BP-DES) or second-generation durable polymer drug-eluting stents (DP-DES). The purpose of this study was to investigate the safety and efficacy of BP-DES and compare that with DP-DES in patients with and without CPCI during a 5-year follow-up. METHODS: Patients who exclusively underwent BP-DES or DP-DES implantation in 2013 at Fuwai Hospital were consecutively enrolled and stratified into two categories based on CPCI presence or absence. CPCI included at least one of the following features: unprotected left main lesion, ≥2 lesions treated, ≥2 stents implanted, total stent length >40 mm, moderate-to-severe calcified lesion, chronic total occlusion, or bifurcated target lesion. The primary endpoint was major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction, and total coronary revascularization (target lesion revascularization, target vessel revascularization [TVR], and non-TVR) during the 5-year follow-up. The secondary endpoint was total coronary revascularization. RESULTS: Among the 7712 patients included, 4882 (63.3%) underwent CPCI. Compared with non-CPCI patients, CPCI patients had higher 2- and 5-year incidences of MACE and total coronary revascularization. Following multivariable adjustment including stent type, CPCI was an independent predictor of MACE (adjusted hazard ratio [aHR]: 1.151; 95% confidence interval [CI]: 1.017-1.303, P  = 0.026) and total coronary revascularization (aHR: 1.199; 95% CI: 1.037-1.388, P  = 0.014) at 5 years. The results were consistent at the 2-year endpoints. In patients with CPCI, BP-DES use was associated with significantly higher MACE rates at 5 years (aHR: 1.256; 95% CI: 1.078-1.462, P  = 0.003) and total coronary revascularization (aHR: 1.257; 95% CI: 1.052-1.502, P  = 0.012) compared with that of DP-DES, but there was a similar risk at 2 years. However, BP-DES had comparable safety and efficacy profiles including MACE and total coronary revascularization compared with DP-DES in patients with non-CPCI at 2 and 5 years. CONCLUSIONS Patients underwent CPCI remained at a higher risk of mid- to long-term adverse events regardless of the stent type. The effect of BP-DES compared with DP-DES on outcomes was similar in CPCI and non-CPCI patients at 2 years but had inconsistent effects at the 5-year clinical endpoints.
Humans ; Drug-Eluting Stents/adverse effects* ; Myocardial Infarction/complications* ; Polymers/therapeutic use* ; Treatment Outcome ; Coronary Artery Disease/complications* ; Percutaneous Coronary Intervention/adverse effects* ; Absorbable Implants ; Prosthesis Design

Objective:The study takes the Youth Research Project of National Natural Science Foundation of China (NSFC) as an example, analyzes the development and management optimization strategy of such research project in a children′s hospital, to provide reference for the training of pediatric young talents.Methods:Personnel interview and questionnaire survey were adopted to analyze the common characteristics of project application and approval, trend of change, demand and bottleneck challenges of the NSFC Youth Research Project from 2016 to 2022.Results:The total number of approved project were increasing while the rate of the bids fluctuated, and the distribution of department, gender and age are not balanced, full-time scientific research personnel, male, young age and other factors have the advantages of being approved. Five influential factors, including scientific research accomplishment, supporting conditions, research foundation, methods & skills, and scientific research atmosphere and environment, were identified as necessary components of getting funded. The survey also founded that two thirds of the needs run through the whole application process that from the topic selection, nurtured seed-funding, team-building and proposal development.Conclusions:This study puts forward a management plan for youth scientific research projects in children′s hospital from three aspects that including hospital, department and individual. The management department should strengthen the transformation from " full application" to " effective application" , at the same time, more attention should be paid to the selection, training and resource allocation to further optimize the training strategy of youth talents.