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

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Objective:To investigate and analyze the employment status of college graduates majoring in health service and management in China.Methods:From April 2023 to June 2024, a cross-sectional survey was conducted on undergraduate graduates majoring in health service and management from 34 universities in China using convenient sampling method. General information was collected (such as gender, household registration at graduation, only child status, average monthly family income, previous experience as a student cadre, average grade point, part-time job experience, entrepreneurial experience, whether a first batch graduate of the university and the major, self-assessment of professional competence level) alongside employment status. Statistical descriptive analysis was employed to analyze the graduates′ basic employment situation, job competence and professional skill demand, types of certificates valued by employers, factors influencing job selection, evaluation of work and profession, and perceptions of professional employment prospects. A total of 1 417 questionnaires were collected in this study, with 1 315 valid responses (92.8%). Chi-square tests were used to compare employment differences among various factors, and binary logistic regression was used to analyze factors influencing employment outcomes.Results:Among 564 employed graduates in the Health Services and Management field, 98 (17.4%) work in health management companies and 97 (17.2%) in hospitals. Regarding important job competencies, 413 (73.2%), 409 (72.5%), and 364 (64.5%) respectively emphasized the importance of information collection and statistical analysis, organizational coordination, and communication skills. Key professional skills highly valued by employers included health risk assessment 175 (66.3%), health measurement 160 (60.6%), and health education and promotion 152 (57.6%). Additionally, 281 (49.8%) highlighted the importance of Health Management Professional Qualification Certificates. Factors influencing job choices included salary and benefits 454 (80.5%) and personal interests and hobbies 279 (49.5%). While 397 (70.4%) of the graduates provided positive feedback on their profession, only 274 (48.6%) were optimistic about their future job prospects. Binary logistic regression analysis indicated significant correlations (all P<0.05) between employment outcomes and factors such as part-time work experience ( OR=1.31) and average grade point ( OR=0.61, 0.68). Conclusions:The employment rate of undergraduate graduates majoring in health service and management in China is low in the health service market, with a low degree of job specialization matching. Graduates are not optimistic about the future employment prospects in their field, possibly due to unclear positioning in talent cultivation in universities and an imperfect job market.

Objective To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation.Methods A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024.Additionally,a literature review was conducted.Results All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels,and one child was initially identified through neonatal genetic metabolic disease screening.According to the literature review,there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation(including the four children in this study).Among these,12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome,while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine(C5-OH)during neonatal genetic metabolic disease screening.Conclusions Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome,detectable as early as during neonatal genetic metabolic disease screening.

Objective:Chronic obstructive pulmonary disease(COPD)is a significant global public health issue.Modern medical treatments have both benefits and limitations,prompting increasing attention from scholars worldwide on traditional ethnic medicine,and the Zangsiwei Qingfei Mixture is a newly developed formula derived from the effective components of classical Tibetan medicine to treat chronic respiratory diseases.This study aims to investigate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods:Sixty AECOPD patients admitted to the Second Xiangya Hospital of Central South University from May 2021 to May 2023 were enrolled and randomly divided into 2 groups,with 30 patients in each group.The control group received conventional treatment,including bronchodilators,anti-infection agents,expectorants,and oxygen therapy.The experimental group received the Zangsiwei Qingfei Mixture in addition to conventional treatment.The treatment duration was 7 d for both groups.Baseline data such as gender,age,body mass index(BMI),smoking status,Global Initiative for Chronic Obstructive Lung Disease(GOLD)classification,COPD course,and the number of COPD exacerbations in the past year were collected.The primary efficacy indicators were assessed using the modified Medical Research Council(mMRC)dyspnea scale and the modified Borg scale.Secondary indicators included arterial lactic acid(LAC)and serum tumor necrosis factor alpha(TNF-α)levels.Safety indicators included liver and kidney function[alanine transaminase(ALT),aspartate transaminase(AST),serum creatinine(SCr),serum uric acid(SUA)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(FIB),and D-dimer].The generalized linear mixed model(GLMM)was used to evaluate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture. Results:Before treatment,there were no statistically significant differences in general baseline data,grading of mMRC dyspnea scale,score of modified Borg scale,arterial LAC,ALT,AST,SCr,SUA,APTT,FIB,and D-dimer between the 2 groups(all P＞0.05).However,serum TNF-α and PT levels in the experimental group were significantly lower than those in the control group(both P＜0.05).GLMM analysis showed that after adjusting for pre-and post-treatment,gender,age,BMI,smoking status,GOLD classification,COPD course,and the number of COPD exacerbations in the past year,the experimental group demonstrated significantly lower grading of mMRC dyspnea scale(coefficient=-0.329,P=0.036),score of modified Borg scale(coefficient=-1.077,P=0.001),serum TNF-α level(coefficient=-14.378,P＜0.001),and arterial LAC level(coefficient=-0.409,P=0.012)compared to the control group.The Zangsiwei Qingfei Mixture had no significant effect on liver,kidney,or coagulation function indicators(all P＞0.05). Conclusion:The Zangsiwei Qingfei Mixture combined with conventional treatment can improve clinical symptoms and promote homeostasis in AECOPD patients,demonstrating safety and reliability.Combining modem medicine with traditional ethnic medicine offers a feasible approach to treating chronic respiratory diseases in the future.

Background: Single room isolation with contact precautions is widely regarded as a fundamental strategy to prevent the transmission of multidrug-resistant organisms (MDROs). However, its implementation demands substantial resources, limiting its universal application to all MDROs. In this study, we assessed the effect of discontinuing single room isolation for vancomycin-resistant Enterococcus (VRE). Methods: This is a retrospective, observational study conducted at a single 750-bed tertiary center. We conducted an interrupted time series analysis to compare incidence rates and trends of new-onset VRE colonization and bacteremia during the one year before and after the strategy change on January 1, 2023. Results: Single-room occupancy decreased from 79.7% pre-intervention to 23.6% postintervention (P < 0.001). The incidence rate of new-onset VRE colonization was 0.452 and 0.535 per 1,000 patient-days in the pre- and post-intervention periods, respectively, with no statistically significant difference (P = 0.202). However, there was a slightly increasing trend (0.036 [95% confidence interval, −0.002, 0.074] increase per month, P = 0.066). The new-onset VRE bacteremia incidence rate was not differed in incidence (0.060 and 0.055, P= 0.571) or trend (P = 0.720). Conclusion Our study suggests that discontinuing single-room isolation for VRE patients may not affect the incidence of new-onset VRE bacteremia, but caution is needed due to the potential increase in colonization.