Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.

Objective To establish a method for testing isolated mitral valve in vitro and quantitatively evaluate the effect of transcatheter edge-to-edge repair technology(TEER)on functional mitral regurgitation(FMR)(non-A2-P2 regurgitation).Methods In this study,an FMR(non-A2-P2 regurgitation)model was developed by dilating the annulus orifice and displacing the papillary muscle in isolated porcine mitral valve.The hydrodynamics characteristics of 6 valves were tested by a pulsatile flow testing system under different physiological and pathological conditions before and after TEER.Results The results show that the valve regurgitation improved from moderate-severe[regurgitant fraction(60.2±17.5)％]to mild-moderate[regurgitant fraction(34.7±12.0)％]by repair(P＜0.001).The EOA[(3.8±1.6)cm2 vs.(2.2±0.5)cm2,P＜0.001]and the forward cross valve pressure difference[(1.8±1.3)mmHg vs.(3.8± 1.8)mmHg,P＜0.001],which characterize the forward flow performance of the valve,were compared before and after repair,and the differences were statistically significant.At the same time,the repair caused valve stenosis(the effective orifice area decreased by 40％and the positive differential pressure increased by 110％),but the valves was still within the normal physiological range,and no iatrogenic stenosis was caused.Conclusions It can be seen that TEER has an effect on FMR.This study provides validation and evaluation methods in vitro for expanding indications and improving TEER,and reference for developing standards of transcatheter valve repair testing in vitro.

Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.

DNA replication is a fundamental DNA metabolism process in living organisms. In human cells, thousands of DNA replication origins are activated simultaneously within the chromatin environment to initiate the replication process and eventually complete genome duplication. This process is regulated by the chromatin environment and coordinated with other chromatin metabolism events, ensuring accurate inheritance of genomic and epigenetic information. With the rapid development of research techniques and the massive accumulation of research data, the systematic understanding of DNA replication in eukaryotic cells, especially in mammals, within complex chromatin environments is a future research trend. Here, we review the multilayered regulatory modes of DNA replication from initiation to termination in the chromatin environment, offering insights for future research.

Objective: To investigate the effect of activation of the stimulator of interferon genes(STING) pathway on macrophage polarization function and its role in T-cell response. Methods: Mouse macrophage RAW264.7 cells were used.STING signaling related proteins in RAW264.7 macrophage treated with STING agonist diABZI were analyzed by Western blot,including TANK-binding kinase-1(TBK1),interferon regulatory factor-3(IRF3),STING,p-TBK1,p-IRF3,p-STING.The polarization of macrophage RAW264.7 cells treated with diABZI was analyzed by flow cytometry.Co-culture of diABZI-treated RAW264.7 macrophage and T cells was applied to evaluate the change of T cell response. Results: STING signaling related proteins were upregulated in macrophage RAW264.7 cells treated with diABZI for 3 hours.The expression of CD86 was upregulated on the surface of macrophages after 12 hours of diABZI treatment,and the CD86/CD206 ratio was elevated,which presented the M1 polarization phenotype.When coculturing diABZI-treated macrophage RAW264.7 cells with T cells,the cytokine secretion ability of T cells including CD4+T and CD8+T cells was enhanced and the expression of CD107a in CD8+T cells was upregulated. Conclusion STING signaling induces M1 polarization of macrophages which enhance the function of T cells,especially CD8+T cell immune response.

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.