BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.

Analgesia is an important link in the treatment of severe patients after neurosurgery and plays a vital role in improving the prognosis of the patients.Understanding the status quo and influencing fac-tors of pain in severe patients after neurosurgery helps to predict the occurrence of pain,which is crucial for determining the new pain assessment methods and auxiliary analgesic methods and developing novel analgesic drugs.This paper reviews the pain status,pain evaluation and analgesic methods of severe patients after neuro-surgery in recent years so as to understand the pain management current status of the patients with severe neurological conditions and provide reference for the medical staff to implement the analgesic programs.

Objective:To investigate whether 6-shogaol (6-SH) alleviates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal autophagy and calcium overload by promoting the expression of microRNA-26a-5p (miR-26a-5p) and inhibiting death-associated protein kinase 1 (DAPK1), and to explore its potential mechanisms.Methods:Primary cultured logarithmic growth phase mouse hippocampal neurons HT22 cells were taken and cell counting kit-8 (CCK-8) was used to detect cell viability, searching for the optimal concentration of Na 2S 2O 4. HT22 cells were divided into blank control group (NC group), OGD/R group (sugar-free culture medium + 10 mmol/L Na 2S 2O 4 treatment for 1.5 hours followed by normal culture medium for 4 hours), 6-SH intervention group (cultured with 10 μmol/L 6-SH for 4 hours after OGD), negative control inhibitor pretreatment group (transfected with negative control inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours), and miR-26a-5p inhibitor pretreatment group (transfected with miR-26a-5p inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours). Cell viability of each group was detected by CCK-8 method; cell ultrastructure was observed under transmission electron microscopy; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of DAPK1 and miR-26a-5p; molecular docking were used to verify the interaction between 6-SH and miR-26a-5p; dual-luciferase assay was used to verify the targeting relationship between DAPK1 and miR-26a-5p; flow cytometry was used to determine the levels of intracellular Ca 2+; Western blotting was used to detect the protein expressions of phosphorylated-glutamate receptor 2B (p-NMDAR2B) Ser1303, DAPK1, autophagy related protein Beclin1, light chain 3 (LC3), and p-DAPK1 Ser308; immunofluorescence was used to detect the expression of LC3 and Beclin1. Results:The results of the CCK-8 assay showed that the cell viability of the 6-SH intervention group was significantly increased compared to the OGD/R group, while the cell viability of the miR-26a-5p inhibitor pretreatment group was significantly decreased compared to the 6-SH intervention group. Transmission electron microscopy revealed that the number of autophagosomes in the 6-SH intervention group was significantly reduced compared to the OGD/R group, while the number of autophagosomes in the miR-26a-5p inhibitor pretreatment group was significantly increased compared to the 6-SH intervention group. RT-qPCR results showed that compared with the OGD/R group, the expression of miR-26a-5p was significantly upregulated and the expression of DAPK1 mRNA was significantly downregulated in the 6-SH intervention group; compared with the 6-SH intervention group, the expression of miR-26a-5p was significantly downregulated and the expression of DAPK1 mRNA was significantly upregulated in the miR-26a-5p inhibitor pretreatment group. Molecular docking verified the interaction between 6-SH and miR-26a-5p. Dual-luciferase reporter gene assay showed that compared with the negative control group, mmu-miR-26a-5p significantly downregulated the luciferase expression of m-DAPK1-3UTR-WT, indicating a binding interaction between them. Flow cytometry results showed that compared with the OGD/R group, the level of intracellular Ca 2+ was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the level of Ca 2+ was significantly increased in the miR-26a-5p inhibitor pretreatment group. Western blotting results showed that compared with the OGD/R group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly decreased in the 6-SH intervention group (p-NMDAR2B Ser1303/β-actin: 2.34±0.27 vs. 4.78±0.39, DAPK1/β-actin: 1.40±0.13 vs. 2.37±0.21, Beclin1/β-actin: 2.61±0.32 vs. 4.32±0.29, LC3/β-actin: 2.52±0.45 vs. 5.09±0.18, all P < 0.05), while the protein expression of p-DAPK1 Ser308 was significantly increased (p-DAPK1 Ser308/β-actin: 0.66±0.09 vs. 0.40±0.02, P < 0.05); compared with the 6-SH intervention group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly increased in the miR-26a-5p inhibitor pretreatment group (p-NMDAR2B Ser1303/β-actin: 4.08±0.14 vs. 2.34±0.27, DAPK1/β-actin: 1.96±0.15 vs. 1.40±0.13, Beclin1/β-actin: 3.92±0.31 vs. 2.61±0.32, LC3/β-actin: 4.33±0.33 vs. 2.52±0.45, all P < 0.05), while the expression of p-DAPK1 Ser308 protein was significantly decreased (p-DAPK1 Ser308/β-actin: 0.33±0.12 vs. 0.66±0.09, P < 0.05); immunofluorescence staining showed that compared with the OGD/R group, the fluorescence intensity of LC3 and Beclin1 was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the fluorescence intensity of LC3 and Beclin1 was significantly increased in the miR-26a-5p inhibitor pretreatment group. Conclusion:6-SH can alleviate neuronal damage by regulating miR-26a-5p/DAPK1 to reduce autophagy and calcium overload in cells.

Objective To investigate the effects of a 45％high-fat diet(HFD)with isocaloric intake on energy metabolism and endurance exercise capacity in SD rats.Methods Twenty-four male SD rats were randomly divided into normal chow diet group(CON),HFD group,normal chow diet+exercise training group(CONT),and HFD+exercise training group(HFDT).The CON and CONT groups received normal chow diet,while the HFD and HFDT groups received a 45％high-fat diet with isocaloric intake.The HFDT and CONT groups underwent an endurance training of moderate-intensity running for 6 weeks.Body weight,fat mass,and lean mass were measured weekly.Energy expenditure and basal metabolic rate during rest and exercise states were measured using Pheno Master/Calo Treadmill system.Blood glucose,lipids,and creatine kinase levels were detected after the exhaustion test.Results In 6 weeks after intervention,the endurance exercise capacity was significantly enhanced in the HFDT group than the CONT group(P＜0.05).There were no obvious differences in body weight and body composition among the groups under isoenergetic feeding conditions.At rest,no statistical differences were observed in total energy expenditure and basal metabolic rate among the groups.However,prior to the 4th week,the CON group primarily metabolized carbohydrates while the HFD group primarily metabolized fats.But the carbohydrate metabolism was decreased and then increased,and the substrate metabolism rates eventually reached similar levels between the 2 groups on the 5th to 6th week.The HFDT group primarily metabolized fats while the CONT group primarily metabolized carbohydrates,with significant differences persisting after 6 weeks of training(P＜0.05).HFD led to elevated levels of serum cholesterol,triglycerides(TG),and high-density lipoprotein cholesterol(HDL-C),but,endurance training resulted in decreased lipid levels in the HFDT group,accompanied by an increase inβ-hydroxybutyrate(βHB)level(P＜0.05).Isoenergetic diets had no significant differences in their effects on liver and kidney function or muscle damage indicators.Conclusion An isoenergetic HFD can improve fat utilization ability and extend endurance exercise time in rats without altering body composition or affecting liver and kidney function.

Objective To investigate the expression of magnesiun transporter 1 protein(MagT1)in peripheral blood T lymphocytes of patients with systemic lupus erythematosus(SLE),and elucidate its clinical significance.Methods A total of 79 SLE patients admitted to the People's Hospital of Xishuangbanna Dai Autonomous Prefecture from January 2019 to June 2021 were selected as the study subjects,and SLE patients were divided into moderate to severe group(SLEDAI ≥ 10,n=32)and mild group(SLEDAI＜10,n=47),according to SLE disease activity index(SLEDAI)score.Another 40 healthy patients who underwent physical examinations during the same period were selected as control group.The levels of clinical biochemical and serum immune-related indexes were recorded.The expressions of MagT1 mRNA and protein in peripheral blood T lymphocytes were detected by quantitative real-time PCR(qRT-PCR)and Western Blot methods.The correlation between the expression of MagT1 protein in peripheral blood T lymphocytes and biochemical and immunity-related indexes was analyzed by Pearson correlation analysis.Receiver working characteristic(ROC)curve was drawn to analyze the diagnostic value of MagT1 protein expression of peripheral blood T lymphocytes in diagnosing SLE and its severity.Results Compared with the control group,the expression levels of MagT1 mRNA[0.65(0.36,0.99),0.23(0.07,0.36)vs 1.20(0.83,1.37)]and MagT1 protein[0.35(0.22,0.42),0.22(0.15,0.27)vs 0.53(0.40,0.63)]of peripheral blood T lymphocytes in the mild group and the moderate to severe group were reduced,with significant differences(Z=5.247,7.078;5.128,7.257,all P＜0.05).Compared with the mild group,the expression levels of MagT1 mRNA[0.65(0.36,0.99)vs 0.23(0.07,0.36)]and protein[0.35(0.22,0.42)vs 0.22(0.15,0.27)]of peripheral blood T lymphocytes in the moderate to severe group were reduced,with significant differences(Z=5.169,3.599,all P＜0.05).Pearson correlation results showed that MagT1 protein expression in peripheral blood T lymphocytes was positively correlated with serum hemoglobin(HGB),complement 3(C3)and C4 levels(r=0.496,0.637,0.588,all P＜0.05),but was negatively correlated with serum erythrocyte sedimentation rate(ESR),hypersensitive C-reactive protein(hs-CRP),IgG levels and SLEDAI(r=-0.598,-0.476,-0.646,-0.514,all P＜0.05).The results of the ROC curve showed that the area under the curve in diagnostic SLE for the expression level of peripheral blood T lymphocyte MagT1 protein was 0.893(95％CI:0.838～0.948),with a sensitivity and a specificity of 90.0％and 67.1％,respectively,and the area under the curve in diagnostic SLE severity was 0.739(95％CI:0.631～0.848),with a sensitivity and a specificity of 57.4％and 84.4％,respectively.Conclusion The expressions of peripheral blood T lymphocyte and MagT1 were down regulated in SLE patients,and they had a negative trend with the severity of SLE.They may have a certain diagnostic value for the diagnosis and severity of SLE.

Objective To explore the effects of remote ischemic preconditioning combined with permissive hypercapnia on brain oxygen saturation and postoperative cognition in patients which undergoing thoracoscopic lung cancer surgery.Methods A collection of 64 patients elective requiring thoracoscopic lung cancer surgery who were divided into control group and combined group according to the randomized grouping method,with 32 cases in each group.The PaCO2 in the control group of patient was maintained at normal,and patients in the combination group were given permissive hypercapnia ventilation strategies and performed remote ischemic preconditioning,PaCO2 is maintained at 45-50mmHg(1mmHg=0.133kPa).Record the cerebral oxygen saturation(rSO2)at the five time points before operation(T0),10min after one lung ventilation(T1),30min after one lung ventilation(T2),10 min after lung recruitment(T3)and the end of surgery(T4),measured the internal jugular venous blood oxygen saturation(SjvO2)and calculated cerebral arteriovenous blood oxygen content difference(CaO2-CjvO2),brain oxygen uptake rate(CERO2).Monitored the average arterial pressure(MAP)and heart rate(HR)of the hemodynamic indicators at the above five time points.The scores of cognitive function were recorded 1 day before operation and 1 day and 3 days after operation;detected the levels of serum neuron-specific enolase(NSE),amyloid β(Aβ)and S100β protein(S100β)in 1 day before surgery,24hours after surgery and 48hours after surgery;Comparison of postoperative related indicators and adverse reactions between the patients of two groups.Results The rSO2 and SjvO2 of combined group were higher than control group in the T1-T4,but CaO2-CjvO2 and CERO2 were lower than those of control group.There was no significant difference in HR and MAP between two groups from T0-T4.The mini-mental state examination(MMSE)score of the combined group was significantly higher than that of the control group on the 1 day after operation.The level of serum NSE,Aβ and S100β in the combined group was lower than those of control group at 24hours and 48hours after operation.There was no significant difference in incidence of postoperative adverse reactions and postoperative related indexes between the two groups.Conclusion Permissive hypercapnia combined with remote ischemic preconditioning can increase cerebral oxygen saturation in patients undergoing thoracoscopic lung cancer surgery,improve cerebral oxygen metabolism and reduce the levels of serum neuron-specific enolase,β-amyloid protein and S100β protein,decrease the postoperative cognitive dysfunction.

Cerebral small vessel disease （CSVD） is a dynamic vascular disease of the cerebrovascular system caused by various etiologies， resulting in a series of clinical， imaging， and pathological manifestations. With the increase in human life expectancy， CSVD has attracted much attention due to its high incidence and recurrence rates. With the research advances in imaging and neurophysiology， some progress has been made in the pathogenesis， diagnosis， and treatment of CSVD. Currently， researchers have found that the study of blood biomarkers for CSVD may help to achieve early diagnosis and intervention and improve prognosis. In addition， the accessibility， simplicity， and convenience of blood biomarkers make them promising for wide clinical application. This article reviews the research advances in blood biomarkers for CSVD.
Biomarkers

ObjectiveTo study the potential quality marker （Q-marker） of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， multivariate statistical analysis （MSA）， and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were employed to screen out the main marker components that caused differences between groups. Moreover， network pharmacology technology was applied to predict the potential "sore throat-relieving" components， and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds， including alkaloids， diterpenoid lactones， and sterols， were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA： Columbamine， jatrorrhizine， palmatine， menisperine， and columbin. Network pharmacology analysis yielded six compounds： tetrahydropalmatine， palmatine， menisperine， fibleucin， neoechinulin A， and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6， epidermal growth factor receptor， prostaglandin G/H synthase 2， matrix metalloproteinase-9， proto-oncogene tyrosine-protein kinase Src and other targets， and regulating Hepatitis B， influenza A， human T-cell virus infection， human cytomegalovirus infection， coronavirus disease-2019， and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine， menisperine， and columbin， which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix， which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

OBJECTIVE: To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years. METHODS: From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups. RESULTS: All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05). CONCLUSION Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.
Male ; Female ; Humans ; Middle Aged ; Aged ; Arthroplasty, Replacement, Hip/methods* ; Treatment Outcome ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Reoperation

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins