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

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

Objective To determine the effects of ciprofol and propofol on hemodynamics and cardiac work were determined by hemodynamic monitoring,so as to provide reference for anesthesia induction in car-diac surgery.Methods A total of 90 patients scheduled for mitral valve replacement under cardiopulmonary bypass from June 2022 to June 2023 were randomly divided into two groups:the ciprofol group (group P,n=45) and the propofol group (group B,n=45).The heart rate (HR),oxygen saturation (SpO2),index of con-sciousness (ICO1),mean arterial pressure (MAP),central venous pressure (CVP),stroke volume (SV),car-diac output (CO),systemic vascular resistance (SVR),cardiac cycle efficiency (CCE),stroke volume variation (SVV),maximum pressure gradient reflecting myocardial contractility (dp/dt) were recorded before adminis-tration (T0) and five min after administration (T1).Results In group P,ICO1,MAP,SV,CO,and SVR at T1 were lower than those at T0,and CCE was higher than that at T0 (P<0.01,P<0.05).In group B,ICO1, MAP,CVP,SV,CO,SVR,CCE,SVV,dp/dt at T1 were significantly lower than those at T0 (P<0.01,P<0.05).There was no statistically significant difference in HR,SpO2,ICO1,MAP,CVP and hemodynamic indi-cators between group B and group P at T0 (P>0.05).There was no statistically significant difference in HR, SpO2,ICO1,CVP and SVV between group B and group P at T1 (P>0.05).MAP,SV,CO,SVR,CCE and dp/dt at T1 in group P were higher than those in group B (P<0.05).Conclusion Ciprofol can better maintain hemodynamic stability and reduce cardiac impairment during the induction phase of mitral valve replacement surgery under cardiopulmonary bypass.

Objective To explore the clinical efficacy of repeated transcranial magnetic stimulation(rTMS)and acupuncture therapy in the treatment of chronic insomnia disorder(CID)patients.Methods A total of 80 patients with CID,who were treated at Nanchang First Hospital from January 2022 to December 2023,were selected for the study.The patients were randomly divided into control group and treatment group,with 40 cases in each group.The control group patients were treated with dexmedetomidine,while the treatment group patients received rTMS and acupuncture therapy in addition to control group.The treatment course was 4 weeks,and the sleep quality,sleep related indicators,and psychological condition improvement of both groups of patients were observed before and after treatment.Results After treatment,the Pittsburgh sleep quality index scores of both groups of patients decreased(P＜0.05);The sleep latency and number of awakenings were lower than before treatment(P＜0.05),and the total sleep time,sleep efficiency,and proportion of rapid eye movement sleep were higher than before treatment,treatment group showed more significant improvement than control group(P＜0.05).After treatment,the Hamilton anxiety and depression scale scores of both groups of patients decreased compared to before treatment,but there was no statistically significant difference in control group before and after treatment(P＞0.05).However,there was a statistically significant difference in treatment group before and after treatment(P＜0.05).Conclusion The combination of rTMS and acupuncture treatment can significantly improve the sleep quality of CID patients,while also reducing the accompanying symptoms of anxiety and depression.

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.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To observe the clinical effect of electrophysiological technique in treating chronic prostatitis.Meth-ods:Choose 40 patients of chronic prostatitis/chronic pelvic pain syndrome(chronicprostatis/chronicpelvicpainsyndrome,CP/CPPS)in People's Hospital in Zhijin and People's hospital in Guizhou Province from January 2022 to April 2023,The patients were randomly divided into control group(n=20)and treatment group(n=20).The treatment group received low-frequency neuromuscular electri-cal stimulation combined with drug therapy,while the control group received drug therapy alone.The improvement of prostatitis symp-tom score(NIH-CPSI)and International Prostatitis Symptom score(IPSS)before and after treatment was compared and analyzed.Results:A total of 37 patients were followed up(1 patient in the treatment group withdrew due to hypersensitivity to the electrode;2 patients in the control group were lost to follow-up.)There was no significant difference in baseline data between the two groups(P>0.05).The NIH-CPSI score and IPSS score before and after treatment were compared between the two groups,and the difference was statistically significant(P<0.05).The IPSS score of the two groups after treatment was compared,the average reduction of the treat-ment group was15.84±0.92 points,and that of the control group was7.17±0.40 points,and the difference was statistically signifi-cant(t=4.792,P<0.05).The NIH-CPSI score of the two groups after treatment was compared,and the average reduction was 17.47±0.92 points in the treatment group and 10.56±0.49 points in the control group.The difference between the two groups was statistically significant(t=6.654,P<0.05).Conclusion:The effect of electrophysiological combined drug therapy is obviously better than that of simple drug therapy.Electrophysiological therapy for chronic prostatitis has definite clinical effect and is worth pro-moting and applying.

The clinical and imaging manifestations of the dural arteriovenous fistula(DAVF)located in the great cerebral vein area with progressive bilateral thalamic edema lack specificity and are easily confused with a variety of diseases.The authors reported a case presented with psychiatric and behavioral abnormalities,followed by bilateral thalamic lesions.Initially,the diagnosis was considered as a glioma of the thalamus,encephalitis and straight sinus thrombosis,but the clinical and imaging findings progressively worsened.Through multi-modal imaging examinations,a DAVF in the great cerebral vein territory was finally diagnosed.By reporting the case and reviewing the literature,this paper aimed to explore the clinical manifestations and imaging features of the disease to reduce the incidence of misdiagnosis.

AP2 transcription factors belong to the AP2/ERF superfamily and are involved in the regula-tion of various biological processes in plant growth and development,as well as in response to biotic and abiotic stresses.However,studies on the AP2 transcription factor family of Perilla frutescens have not been reported.In this study,totally 18 AP2 family members were identified from the Perilla frutescens ge-nome and analyzed for gene structure,conserved motifs,and cis-acting elements using bioinformatics.WRINKLED1(WRI1)is a key regulator of lipid biosynthesis in many plant species and plays an impor-tant role in the regulation of lipid synthesis.Sequence comparison revealed that one member of WRI1 is highly homologous to AtWRI1 and contains two conserved AP2 domains,named PfWRI1.The expression levels of PfAP2 family genes were analyzed in different tissues of Perilla frutescens and at different stages of seed development in conjunction with the transcriptome data,and the results showed that PfWRI1 is highly expressed only in the seeds of Perilla frutescens,suggesting that PfWRI1 may be related to the de-velopmental process of the seeds.The overexpression vector of plant pCAMBIA1303-PfWRI1 was con-structed,and wild-type(Col)and mutant(wri1-1)Arabidopsis thaliana were transformed by Agrobacte-rium tumefaciens to obtain overexpression and complementation lines,respectively.The results showed that the expression of P fWRI1 led to an increase in oil content of Arabidopsis seeds by 8.90％-13.57％compared with Col,and promoted the accumulation of oleic acid(C18:1)and linoleic acid(18:2)and reduced the accumulation of palmitic acid(C16:0),arachidonic acid(C20:0),and cis-11-Eicosenoic acid(C20:1)in transgenic Arabidopsis seeds.In addition,PfWRI1 gene expression increased the ex-pression of glycolysis and fatty acid biosynthesis-related genes AtPKP-α,AtPKP-β1,AtBCCP2,AtSUS2,and AtLIP1.Taken together,PfWRI1 may promote lipid accumulation by increasing unsaturated fatty acid content through interaction with the above genes.