BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Objective To analyze the causal relationship between genetically predicted body mass index(BMI)and prostate cancer(PCa)risk with Mendelian randomization(MR),in order to explore the potential risk factors for PCa and the development of prevention strategies.Methods Two-sample MR was performed using BMI genome-wide association study(GWAS)data of 339 224 samples and PCa GWAS data of 463 010 samples.After that,69 single nucleotide polymorphisms(SNP)of BMI were used as instrumental variables to perform MR analysis on PCa.MR analysis adopted the inverse variance weighting method(IVW),MR-Egger method,weighted median method(WME),simple mode method(SM)and weighted mode method(WM).Heterogeneity test,plciotropy test and leave-one-out sensitivity test were used to verify the stability and reliability of the data.Results In the IVW analysis,it was found that BMI was associated with the risk of PCa(OR:0.997,95％CI:0.995-0.999,P=0.001).In the WME(OR:0.996,95％CI:0.994-0.999,P=0.009),and WM(OR:0.995,95％CI:0.991-1.000,P=0.045),the same results were obtained.There was no statistical significant difference between the MR-Egger method(OR:0.996,95％CI:0.991-1.002,P=0.205)and SM(OR:0.995,95％CI:0.990-1.000,P=0.079).Conclusion There is a causal relationship between a genetically predicted higher BMI and a lower risk of PCa by two sample MR analysis.This finding can prove a reference for identifying potential risk factors for PCa and the development of prevention strategies.

Objective To explore the correlation between healthcare-associated infection(HAI)and partial inde-xes in the diagnosis-related groups(DRGs)of patients in thoracic surgery intensive care unit(ICU).Methods DRGs,case mix index(CMI),relative weight(RW),and HAI of patients in thoracic surgery ICU and four subspe-cialty departments(pulmonary surgery group,esophageal surgery group,mediastinum group[mainly thymic sur-gery],and trachea group)in a tertiary chest hospital in Shanghai from January to December 2022 were retrospec-tively analyzed and compared through DRGs index grouping.Results A total of 1 429 patients in the department of thoracic surgery ICU were analyzed,including 59 HAI cases,with a HAI rate of 4.13％.The incidences of HAI in pulmonary surgery group,esophageal surgery group,mediastinum group and trachea group were 3.74％(30/803),5.84％(25/428),1.27％(2/157)and 4.88％(2/41),respectively.There was no statistically significant differ-ence in the incidences of HAI among different subspecialty groups(P＞0.05).A total of 35 DRGs were involved,with CMI of 2.75,3.41,2.35 and 1.25 in pulmonary surgery group,esophageal surgery group,mediastinum group and trachea group,respectively,and RW ranged from 0.53 to 12.62.In the pulmonary surgery group,inci-dence of HAI in male patients was higher than that in female patients.Higher RW score level was associated with higher incidence of HAI.Differences were all statistically significant(all P 0.05).Among patients in the esophageal surgery group,the age of HAI group was higher than that of the non-HAI group(P＜0.05).Higher RW score level was associated with higher incidence of HAI(P＜0.05).Among patients in the mediastinum sur-gery group,the age of patients in the infected group was higher than that in the non-infected group(P＜0.05).Among the 59 HAI cases,31 were infected with MDROs.Conclusion Focusing on CMI and RW in the DRGs in-dex system,analyzing HAI from the perspectives of disease complexity and overall technical difficulties of medical services can provide reference for the precise management of HAI in the new era.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

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.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.