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

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Cosmetics may be an important source of human exposure to per-and polyfluoroalkyl substances(PFASs),posing risks to human health.In this study,a nontarget screening method for PFASs in cosmetics was developed using ultra-high performance liquid chromatography-high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)based on the Kendrick mass defect(KMD).The sample was extracted by ultrasonic assisted extraction prior to being analyzed by UHPLC-Q-Orbitrap HRMS.Acquisition of HRMS data was achieved in both full scan and data-dependent(Full MS/dd MS2)mode.The data collected by HRMS were imported into an in-lab built R script for processing.Samples retained the mass spectra peaks with KMD values in the range of 0.85-1 or 0-0.15 for in-and out-of-library matching;when KMD deviation(δKMD)<0.001 and CF 2 mass error(δMS)<15 ppm,it was considered as a potential PFASs homologues.According to matches of parent ions(MS),fragment ions(MS2)and retention time(RT)with the in-house built PFASs database,the screened and identified potential PFASs were categorized to 5 confidence levels(CL1-CL5).A total of 15 kinds of PFASs homologues with confidence level of CL3 and above were screened from 13 cosmetics products and 8 cosmetic raw materials,including perfluoroalkyl alcohol,hydroperfluoroalkyl sulfonic acid,chloroperfluoroalkyl sulfonic acid,etc.with concentrations ranging from 1.9 ng/g to 98.1 ng/g.The nontarget screening method could be used to screen and identify PFASs homologues feasibly and therefore provided data basis for management and control of PFASs addition in cosmetics.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).