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

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

Objective To establish an animal model of osteoporosis combined with liver cirrhosis and conduct preliminary investigation into the effect of liver cirrhosis on bone loss in mice and the underlying mechanisms.Methods The experimental animals were 25 6-week-old female C57BL/6 mice with a body weight of approximately 20-22 g.A comorbidity model of liver cirrhosis and osteoporosis was established in the mice by ovariectomy combined with carbon tetrachloride(CCl4)induction.The mice were randomly assigned to 4 groups(n=5 in each group),including a control group,a liver cirrhosis group,an osteoporosis group,and a cirrhosis and osteoporosis comorbidity group.Pathological changes in the liver were observed via HE staining,Sirius Red staining,and serum liver function indicators.Bone mass and morphological changes were assessed using micro-CT and HE staining.ELISA,Western blot,and immunohistochemistry were performed to assess the expression of insulin-like growth factor-1(IGF-1)in serum and liver tissues.An additional IGF-1 intervention group was established to investigate the potential role of IGF-1 in the comorbidity of liver cirrhosis and osteoporosis,and changes in bone mass and morphology were analyzed via micro-CT and HE staining.Results Compared with the control and osteoporosis groups,the liver cirrhosis and cirrhosis-osteoporosis comorbidity groups exhibited significant inflammatory cell infiltration and collagen fiber deposition in liver tissues,along with markedly increased serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)(P＜0.05).According to the Micro-CT and HE staining results,the cirrhosis-osteoporosis comorbidity group showed reduced bone mass and decreased trabecular numbers in the distal femur compared to those in the osteoporosis group,with the differences being statistically significant(P＜0.05).ELISA,Western blot,and immunohistochemistry demonstrated significantly reduced expression of IGF-1 in the liver and serum of the cirrhosis-osteoporosis comorbidity group(P＜0.05).Notably,exogenous IGF-1 treatment restored bone mass in mice with liver cirrhosis combined with osteoporosis(P＜0.05).Conclusion Through ovariectomy combined with CCl4 induction,a mouse model of liver cirrhosis combined with osteoporosis was successfully established.IGF-1 may serve as a potential molecular mechanism and therapeutic target mediating the liver cirrhosis-osteoporosis comorbidity.

Objective: To explore the prevalence of screening myopia and depressive symptom among primary and secondary school students in Xuzhou, and to explore the association of sleep and screen time on the coexistence of screening myopia and depressive symptom, so as to provide scientific references for developing intervention strategies to address the development of myopia and promote mental health in children and adolescents. Methods: From September to October 2024, a stratified cluster random sampling method was used to select 6 605 students in grade 4 to 12 in 2 urban and 2 suburban districts in Xuzhou. The students health condition and influencing factors questionnaire were used to assess students basic information, sleep time, and screen time. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess primary and secondary school students depressive symptom.Unaided distance visual acuity examination was conducted, and refractive assessment was performed using an automated refractometer without cycloplegic agents. The Chi-square test and multiple Logistic regression analysis were used to evaluate the association of sleep and screen time with the coexistence of screening myopia and depressive symptom. Results: The detection rates of screening myopia, depressive symptom, and screening myopia and depressive symptoms co morbidity among primary and secondary school students in Xuzhou were 60.35%, 4.45% and 18.61% respectively. Results from the multinomial Logistic regression analysis, using the healthy group as the reference and after adjusting for confounding factors, showed that students with insufficient sleep duration were more likely to have depressive symptom ( OR=1.57, 95%CI =1.08-2.27) and the coexistence of screening myopia and depressive symptom ( OR=1.85, 95%CI =1.45-2.36). Students with daily screen time≥2 h were more likely to have depressive symptom only ( OR=1.41, 95%CI =1.04-1.93) and the coexistence of screening myopia and depressive symptom ( OR=1.31, 95%CI =1.06-1.61). Further stratified analysis based on sufficient and insufficient sleep duration revealed that only in the insufficient sleep duration group, students with daily screen time≥2 h had an increased risk of depressive symptom only ( OR=1.49, 95%CI =1.07-2.07) and the coexistence of screening positive myopia and depressive symptom ( OR=1.40, 95%CI =1.11- 1.77 ) (all P <0.05). Conclusions Primary and secondary school students with insufficient sleep duration and daily screen time≥2 h have higher risks of depressive symptoms and the coexistence of screening myopia and depressive symptoms. It is recommended to ensure adequate sleep duration and limit screen time for children and adolescents.

Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.

Objective:To analyze the current policy design of outpatient benefit policies for patients with hypertension and diabetes(H&D)in urban and rural residents in China,and to provide references for optimizing the outpatient benefit mechanism for patients with H&D.Methods:A questionnaire survey was conducted to collect data on the basic features of General Outpatient Benefit(GOB),Outpatient Medication Guarantee Mechanisms for Hypertension and Diabetes(OMGM-H&D)and Outpatient Benefit for Patient with Chronic and Special Diseases(OB-C&S),focusing on deductibles,policy reimbursement ratios,and maximum payment limits.Descriptive statistical analysis was performed on the data.Results:A total of 334 regions were surveyed,of which 253 regions(75.34％)had implemented all three policies.Regional analysis revealed significant differences(P<0.001)in reimbursement ratios for GOB and the OMGM-H&D between the eastern,central,and western regions,with the western region having notably higher ratios than the eastern and central regions.However,no significant difference (P>0.05) was observed in the reimbursement ratios for OB-C&S across regions. Regarding deductibles,no significant regional difference (P>0.05) was found for GOB,but significant differences (P<0.05) existed for the OMGM-H&D and OB-C&S. Additionally,the annual maximum payment limits for all three policies showed significant regional variations (P<0.001). Conclusions:The outpatient benefits policy for patients with H&D have achieved full coverage nationwide among urban and rural residents in China,but regional equity in benefit levels requires improvement. It is recommended to strengthen data feedback mechanisms and promote provincial-level pooling of medical insurance.

Objective To observe the clinical effect of abdominal full-thickness skin graft combined with adipose stem cells in repairing soft tissue defects after resection of facial benign tumors.Methods A total of 180 patients with soft tissue defects after resection of facial benign tumor in our hospital from January 2019 to June 2022 were selected,the study was designed by a double-blind method,and patients were divided into the observation group and the control group by a random number table method,with 90 cases in each group.Patients in the control group were repaired by abdominal full-thickness skin graft treatment,while these in the observation group were repaired by a combination of abdominal full-thickness skin graft and adipose stem cells.The scar status scores in the surgical area,clinical efficacy,incidence of complications and satisfaction of patients in the two groups were compared.Results Compared with preoperative results,the scores of color and thickness of scars,vascular distribution,and softness in face 6 months after surgery in both groups decreased,with statistically significant differences(P<0.05).Six months after surgery,the observation group had significantly lower scores on scar color and thickness,vascular distribution,and softness compared to the control group(P<0.05);there was no difference in the effective rate of the forehead,nose,eyelids,lips,or cheeks between the observation group and the control group(P>0.05);while the observation group had higher overall effective rate than the control group(P<0.05).There was no statistically significant difference in the incidence of complica-tions between the two groups(P>0.05).There was statistically significant difference in the distribution of the satisfaction of patients between the two groups(P<0.05),and the observation group showed significantly higher satisfaction of patients than the control group(P<0.05).Conclusion Abdominal full-thickness skin graft combined with adipose stem cells can improve facial scars in repairing soft tissue defects after resection of facial benign tumors,and enhance the repair effects and satisfaction of patients,with high safety.

Objective:This study aimed to explore the mediating effect of resourcefulness between frailty and self-manage-ment efficacy in patients with chronic heart failure(CHF).Methods:A survey was conducted on CHF patients who ad-mitted in Department of Cardiology,Central Hospital Affiliated to Shandong First Medical University between May 2022 and March 2024 using the general formation questionnaire,Tilburg weakness assessment scale,Resourcefulness Scale(RS)and Self-Efficacy for Managing Chronic Disease 6-item scale(SEMCD6).Results:Age,employment,marriage,ACC/AHA cardiac function classification,exercise frequency,and comorbid chronic diseases affected the level of frailty in pa-tients;Employed or not affected the patient's resourcefulness level(P＜0.05 or＜0.01).Multivariate linear regression and Spearman correlation analysis showed that frailty was direct negative predictive effect(β=-1.029,P=0.019)and in-versely correlated(r=-0.155,P=0.016)with self-management efficacy;resourcefulness was direct positive predictive effect(β=0.150,P＜0.001)and positively correlated(r=0.336,P＜0.001)with it.Resourcefulness played a partial mediating effect between frailty and self-management efficacy(21.93％).Conclusion:Resourcefulness level plays a par-tial mediating role between frailty and self-management efficacy in patients with chronic heart failure.Medical staff should pay attention to early screening and intervention of resourcefulness level.

Objective:To explore the dosimetry optimization strategy based on filter thickness and shape selection for the bulb superficial X-ray radiotherapy unit.Methods:Monte Carlo code TOPAS was used to model tubular equipment, and the dose distribution from six X-ray energies (50-150 kV) and five conventional aluminum filters (0.5-3.0 mm) with different thickness were simulated in the water model. The percentage depth dose (PDD) curve along the central axis, the center-axis profile dose at different depths, and the lateral dose distribution were analyzed. The dose distribution of three different designs of aluminum filters (conventional cylindrical, conical and oblique cylindrical filters) was compared to evaluate the effect of dosimetric optimization of different filter shapes.Results:Under the same energy, increasing the thickness of the filter can optimize the superficial skin dose, and the optimization effect of depth dose uniformity can be increased by 26% at a depth of 5.5 mm at 70 kV energy. The raised, flat and inclined dose distribution modes can be achieved by using conventional cylindrical, conical and inclined aluminum filters.Conclusions:By selecting the appropriate X-ray energy and filter thickness, an ideal dose distribution matching the tumor depth can be achieved. The application of personalized filters is also of great significance for diverse target areas.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.