Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To analyze the changes in serum levels of neurofilament light chain(NFL),binding protein S100 β(S100 β),and C-reactive protein(CRP)in patients with cognitive impairment after cardiac surgery,and to analyze the correlation between these indicators and patient prognosis.Methods:124 patients with heart disease who underwent surgical treatment from January 2022 to January 2025 were selected.One week after surgery,the patients were evaluated using the Montreal Cognitive Assessment Scale(MoCA).60 patients with MoCA scores＜26 were divided into the cognitive impairment group,and 64 patients with MoCA scores ≥ 26 were divided into the non cognitive impairment group.Compare the general information of two groups,including changes in serum NFL,S100 β,and CRP levels before and after surgery.Using logistic regression to analyze the influencing factors of cognitive impairment after cardiac surgery.Following a 4-month postoperative follow-up,the cognitive impairment group was assessed using the MoCA score.Patients with a MoCA score＜26 were categorized as having a poor prognosis,while the remaining patients were classified as having a good prognosis.The NfL,S100β,and CRP levels in both groups were compared,and the ROC curve was used to evaluate the predictive value of serum NFL,S100β,and CRP for poor prognosis in patients with postoperative cognitive impairment.Results:There was no significant difference in gender,BMI,education level,comorbidities(hypertension,diabetes),disease type,ASA classification,intraoperative blood loss,intraoperative fluid replacement,and cardiopulmonary bypass time between cognitive impairment group and non-cognitive impairment group(P＞0.05).The cognitive impairment group had a higher incidence of age,anesthesia maintenance time during surgery,no analgesia after operation and agitation during awakening than the non-cognitive impairment group(P＜0.05);There was no significant difference in the levels of serum NFL,S100β,and CRP between the two groups of patients before surgery(P＞0.05).On postoperative day 3,the levels of serum NFL,S100β,and CRP increased in both groups,with the cognitive impairment group being higher than the non cognitive impairment group(P＜0.05);Using cognitive impairment(occurrence=1,no occurrence=0)as the dependent variable,logistic regression analysis showed that age,intraoperative anesthesia maintenance time,agitation during the recovery period,postoperative 3-day NFL,S100 β,CRP were independent influencing factors of cognitive impairment after cardiac surgery(P＜0.05);The serum levels of NFL,S100β,and CRP in the good prognosis group and poor prognosis group were higher than those before surgery,and the NFL,S100 β,and CRP levels in the poor prognosis group were higher than those in the good prognosis group before and after surgery(P＜0.05);Using poor prognosis as positive samples and good prognosis as negative samples,a ROC curve was plotted.The results showed that the sensitivity and specificity of the combined prediction of three indicators before and after surgery for poor prognosis of cognitive impairment in cardiac surgery were higher than those of a single indicator(P＜0.05).Conclusion:The serum levels of NFL,S100β,and CRP are significantly elevated in patients with cognitive impairment after cardiac surgery,and the early postoperative elevation of NFL,S100β,and CRP is a contributing factor to the occurrence of cognitive impairment.Preoperative and early postoperative detection of these indicators can predict the prognosis of patients with cognitive impairment after cardiac surgery.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Objective:To investigate the prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Objective:To analyze the changes in serum levels of neurofilament light chain(NFL),binding protein S100 β(S100 β),and C-reactive protein(CRP)in patients with cognitive impairment after cardiac surgery,and to analyze the correlation between these indicators and patient prognosis.Methods:124 patients with heart disease who underwent surgical treatment from January 2022 to January 2025 were selected.One week after surgery,the patients were evaluated using the Montreal Cognitive Assessment Scale(MoCA).60 patients with MoCA scores＜26 were divided into the cognitive impairment group,and 64 patients with MoCA scores ≥ 26 were divided into the non cognitive impairment group.Compare the general information of two groups,including changes in serum NFL,S100 β,and CRP levels before and after surgery.Using logistic regression to analyze the influencing factors of cognitive impairment after cardiac surgery.Following a 4-month postoperative follow-up,the cognitive impairment group was assessed using the MoCA score.Patients with a MoCA score＜26 were categorized as having a poor prognosis,while the remaining patients were classified as having a good prognosis.The NfL,S100β,and CRP levels in both groups were compared,and the ROC curve was used to evaluate the predictive value of serum NFL,S100β,and CRP for poor prognosis in patients with postoperative cognitive impairment.Results:There was no significant difference in gender,BMI,education level,comorbidities(hypertension,diabetes),disease type,ASA classification,intraoperative blood loss,intraoperative fluid replacement,and cardiopulmonary bypass time between cognitive impairment group and non-cognitive impairment group(P＞0.05).The cognitive impairment group had a higher incidence of age,anesthesia maintenance time during surgery,no analgesia after operation and agitation during awakening than the non-cognitive impairment group(P＜0.05);There was no significant difference in the levels of serum NFL,S100β,and CRP between the two groups of patients before surgery(P＞0.05).On postoperative day 3,the levels of serum NFL,S100β,and CRP increased in both groups,with the cognitive impairment group being higher than the non cognitive impairment group(P＜0.05);Using cognitive impairment(occurrence=1,no occurrence=0)as the dependent variable,logistic regression analysis showed that age,intraoperative anesthesia maintenance time,agitation during the recovery period,postoperative 3-day NFL,S100 β,CRP were independent influencing factors of cognitive impairment after cardiac surgery(P＜0.05);The serum levels of NFL,S100β,and CRP in the good prognosis group and poor prognosis group were higher than those before surgery,and the NFL,S100 β,and CRP levels in the poor prognosis group were higher than those in the good prognosis group before and after surgery(P＜0.05);Using poor prognosis as positive samples and good prognosis as negative samples,a ROC curve was plotted.The results showed that the sensitivity and specificity of the combined prediction of three indicators before and after surgery for poor prognosis of cognitive impairment in cardiac surgery were higher than those of a single indicator(P＜0.05).Conclusion:The serum levels of NFL,S100β,and CRP are significantly elevated in patients with cognitive impairment after cardiac surgery,and the early postoperative elevation of NFL,S100β,and CRP is a contributing factor to the occurrence of cognitive impairment.Preoperative and early postoperative detection of these indicators can predict the prognosis of patients with cognitive impairment after cardiac surgery.

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia