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

OBJECTIVES: To study the incidence and disease burden of congenital birth defects in children under five in China from 1990 to 2021 and to predict the incidence of congenital birth defects in this population from 2022 to 2036, providing a reference for the prevention of congenital birth defects in children. METHODS: Using the Global Burden of Disease Study 2021 (GBD 2021) database, the incidence and disability-adjusted life years (DALY) were employed to describe the disease burden. The Joinpoint regression model was used to analyze the trends in incidence and DALY rates of congenital birth defects in children under five. A grey prediction model GM(1,1) was applied to fit the trend of incidence rates of congenital birth defects in this age group and to predict the incidence from 2022 to 2036. RESULTS: In 2021, the incidence rate of congenital birth defects among children under five in China was 737.28 per 100 000. Among these, congenital musculoskeletal and limb deformities had the highest incidence rate at 307.15 per 100 000, followed by congenital heart defects (223.53 per 100 000), congenital urinary and genital tract malformations (74.99 per 100 000), and congenital gastrointestinal malformations (62.61 per 100 000). From 1990 to 2021, the incidence rate and DALY rate of congenital birth defects in children under five in China decreased at an average annual rate of 1.73% and 5.42%, respectively. The prediction analysis indicated a decreasing trend in the incidence of congenital birth defects among children under five in China from 2022 to 2036, with the incidence rate dropping from 892.36 per 100 000 in 2022 to 783.35 per 100 000 in 2036. CONCLUSIONS The incidence and disease burden of congenital birth defects in children under five in China showed a significant declining trend from 1990 to 2021. It is predicted that this incidence will continue to decrease until 2036.
Humans ; Congenital Abnormalities/epidemiology* ; China/epidemiology* ; Incidence ; Infant ; Infant, Newborn ; Child, Preschool ; Female ; Male ; Forecasting ; Disability-Adjusted Life Years

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

AIM To establish the HPLC characteristic chromatogram of Baqi Rougan Decoction reference sample,and to investigate its quantitative transmission laws.METHODS The contents of calycosin 7-O-glucoside,hesperidin,rosmarinic acid,curcumenol and nystose were determined.The transfer rates of decoction piece-aqueous decoction-reference sample were calculated,after which the paste-forming rate and pH value were recorded.RESULTS There were sixteen characteristic peaks in fifteen batches of reference samples with the similarities of 0.90,nine of which were identified.The average transfer rates of nystose and calycosin 7-O-glucoside in the reference sample were(83.14±6.25)%and(77.81±8.31)%,while those of rosmarinic acid and curcumenol in the aqueous decoction-reference sample were(81.71±6.27)%and(72.16±5.91)%,along with the average paste-forming rate and pH value of(38.91%±1.46%)and 5.13±0.08,respectively.CONCLUSION This stable and feasible method can provide a reference for the selection of preparation process and evaluation of key chemical properties for Baqi Rougan Decoction.

Objective To analyse the clinical efficacy of low-frequency of midnight-noon ebb-flow acupuncture-opening method(also called Ziwu Liuzhu Acupuncture,referring to the needling method based on acupoints selection according to qi and blood movement following heavenly-stems and earthly-branches cycle)in treating low myopia in children.Methods A retrospective study was conducted to collect the clinical data of 84 cases(168 eyes)of children with low myopia who received treatment at the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from January 2021 to December 2022.The children were divided into two groups according to the different treatment protocols:42 cases(84 eyes)treated with acupuncture combined with conventional optometry as the control group,and 42 cases(84 eyes)treated with low-frequency of midnight-noon ebb-flow acupuncture-opening method combined with conventional optometry as the observation group,and the treatment course of both groups was 24 weeks.The changes of refractive error and axial length before and after treatment were observed,and the clinical efficacy in the two groups of children were evaluated.Results(1)After treatment,there being statistically significant differences in the refractive error between the two groups of the children(P＜0.05),and the differential value of the refractive error of the children between the two groups before and after treatment was statistically significant(P＜0.05).(2)After treatment,there being statistically significant differences in the axial length of the children in both groups(P＜0.05).The differential value of axial lengths of the children between the two groups before and after treatment was statistically significant(P＜0.05).(3)The total effective rate of the observation group was 84.52%(71/84),and which of the control group was 63.10%(53/84),the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The low-frequency of midnight-noon ebb-flow acupuncture-opening method in treating low myopia in children can effectively postpone the degree of myopia,and decrease the growth of the axis,with exact therapeutic effect.

Objective To study the effects of different doses of vancomycin bone cement on serum inflammatory factors and joint function in patients undergoing total knee arthroplasty.Methods A total of 128 patients who underwent total knee arthroplasty admitted to Handan First Hospital from August 2021 to January 2023 were selected as the study subjects.They were divided into group A(acrylic bone cement without vancomycin),group B(0.5 g vancomycin per 40 g acrylic bone cement),group C(1.0 g vancomycin per 40 g acrylic bone cement)and group D(2.0 g vancomycin per 40 g acrylic bone cement)by random number table method,with 32 patients in each group.High performance liquid chromatography was used to detect the concentration of vancomycin in drainage fluid at different time points after operation of patients in group B,group C,and group D.Immune scattering turbidimetry and Westergren method were used to detect the levels of serum C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)of patients in the four groups before operation,7 days and 6 months after operation.Hospital for special surgery knee score(HSS)was used to evaluate the knee joint function of patients in the four groups before operation and 6 months after operation.Results The concentration of vancomycin in drainage fluid of patients in group B,group C,and group D increased with the increase of dose(P<0.05),and decreased with the extension of time(P<0.05).The postoperative serum CRP and ESR levels in the four groups increasing first and then decreased with time(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group B,group C,and group D were significantly lower than those in group A(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group C and group D were significantly lower than those in group B(P<0.05),while there was no significant difference in serum CRP and ESR levels between group C and group D(P>0.05).The HSS scores 6 months after operation of patients in the four groups obviously improved(P<0.05);the HSS scores 6 months after operation of patients in group B,group C and group D were higher than those in group A(P<0.05);the HSS scores 6 months after operation of patients in group C and group D were obviously higher than those in group B(P<0.05),while there was no obvious difference in the HSS scores 6 months after operation between group C and group D(P>0.05).Conclusion The use of bone cement containing vancomycin can obviously reduce the levels of serum inflammatory factors CRP and ESR in patients undergoing total knee arthroplasty,prevent postoperative infection,and improve joint function of patients.The degree of action of different doses of vancomycin also varies,and it is recommended to use 1.0 g of vancomycin in clinical practice.

[Abstract] Objective To investigate the effect of 6-gingerol treatment on cognitive behavior after hypoxic-ischemic brain injury (HIE) in neonatal mice, and to explore the protective mechanism of 6-gingerol on HIE brain injury in neonatal mice by observing the effects on neuronal survival and neural stem cell proliferation. Methods The right common carotid artery was ligated in Kunming mice (78) on the 7th day after birth and HIE model was established after 90 minutes of hypoxic treatment. 6-gingerol was injected intraperitoneally. The cognitive behavior was detected by Morris water maze test; 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to observe the changes of brain injury; The changes of synaptic structure and number were obseved by transmission electron microscopy; HE staining, Nissl staining and dihydroethidium(DHE) staining were used to observe the pathomorphological changes of hippocampus in each group; The proliferation of neural stem cells and the expression of related transcription factors were detected by immunofluorescence and Real-time PCR; The changes of Akt signal pathway were detected by Western blotting. Results 6-gingerol treatment could improve the long-term learning and memory ability, reduce the brain injury and brain edema of neonatal mice after HIE, and improve synaptic plasticity of mice after HIE. In the 6-gingerol treatment group, the disorder of hippocampal cells in the diseased side of HIE was improved, the number of necrotic cells decreased, the proliferation ability of hippocampal neural stem cells and the expression levels of nestin and sex determining region box transcription factor 2 (Sox2) related transcription factors increased significantly, and the level of phosphorylated Akt (p-Akt) increased. Conclusion It is found that 6-gingerol can improve the learning and memory ability of HIE mice in adulthood and reduce brain tissue injury after HIE. 6-gingerol may play a role in inhibiting the production of reactive oxygen species(ROS), reducing neuronal injury and upregulating the expression of Akt signal pathway, promoting the proliferation of hippocampal neural stem cells, so as to provide potential drugs for the treatment of neonatal HIE.

Objective To test the performances and applicability of the pressure infusion cuff and blood warmer under severe cold environments in the field.Methods Under the severe cold conditions in the field,the simulated hemorrhagic shock patient was placed on a stretcher and transported to a transfer vehicle 2 km away,a pressure infusion cuff and blood warmer was used to perform fluid resuscitation and heating and pressurization blood transfusion during the transport,and the effect of heating and pressurization of the device during the transport was evaluated;two healthy adult male pigs were selected to construct animal models of hemorrhagic shock from war wounds,of which one pig was used as an experimental animal to be treated by blood transfusion with a pressure infusion cuff and blood warmer and the other pig was recognized as a control animal to be treated by blood transfusion using commercially available inflatable pressurized bags and thermostats,and comparison analysis was carried out on the changes in vital signs of animals before and after treatment by the 2 methods of warming and pressurization and the effects of warming and pressurization transfusion.Results The pressure infusion cuff and blood warmer gained advantages in convenience,efficiency and applicability during patient transport;the experimental animal behaved better than the control animal in vital signs such as blood volume,pressure and respiration,transfusion speed and fluid warming.Conclusion The pressure infusion cuff and blood warmer has high efficiency and is applicable under severe cold conditions in the field.[Chinese Medical Equipment Journal,2023,44(11):117-120]