Objective:To investigate the effect of Xuebijing injection against blood-brain barrier(BBB)damage in the mice with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis,and to elucidate its regulatory effect on the imbalance of helper T cells 17(Th17)/regulatory T cells(Treg).Methods:The active immunization models of anti-NMDAR encephalitis in the mice were established using glutamate receptor N1 subunit(GluN1)356-385 antigen peptide,and the serum anti-NMDAR immunoglobulin G(IgG)antibody levels were detected by enzyme-linked immunosorbent assay(ELISA).The healthy mice without modeling were served as control group,and the mice with successful modeling were randomly divided into model group,low dose of Xuebijing injection(XBJ-L)group,and high dose of Xuebijing injection(XBJ-H)group,with 10 mice in each group.After modeling,the mice in XBJ-L and XBJ-H groups were intraperitoneally injected with 5 and 10 mL·kg-1 Xuebijing injection,respectively.The Longa score was used to assess the neurological impairment of the mice in various groups;evans blue(EB)staining was used to determine the BBB permeability;immunofluorescence staining was used to detect the expressions of zonula occludens 1(ZO-1)and Occludin in cerebral cortex of the mice in various groups;Western blotting method was used to determine the expression levels of ZO-1,Occludin,Claudin-5,and neuron-specific nuclear protein(NeuN)in cerebral cortex of the mice in various groups;ELISA method was used to determine the levels of Th17-and Treg-related cytokines including interleukin(IL)-17,IL-22,and IL-10 in serum of the mice;flow cytometry was used to determine the percentages of Th17 and Treg cells in peripheral blood of the mice in various groups,and the Th17/Treg ratio was calculated.Results:The serum of the mice induced with the GluN1 356-385 antigen peptide was positive for NMDAR IgG antibodies,indicating that the models were successfully established.Compared with control group,the neurological impairment score of the mice in model group was significantly increased(P＜0.05),and the EB level in brain tissue was significantly increased(P＜0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were decreased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins in the cerebral cortex were significantly decreased(P＜0.05);the serum levels of IL-17 and IL-22 were significantly increased(P＜0.05),while the IL-10 level was significantly decreased(P＜0.05);the percentage of Th17 cells in peripheral blood was significantly increased(P＜0.05),while the percentage of Treg cells was significantly decreased(P＜0.05),and the Th17/Treg ratio was significantly increased(P＜0.05).Compared with model group,the neurological impairment scores of the mice in XBJ-L and XBJ-H groups were significantly decreased(P＜0.05),the EB levels in brain tissue were significantly decreased(P＜0.05),the fluorescence staining intensities of ZO-1 and Occludin in cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P＜0.05);the levels of IL-17 and IL-22 in serum were significantly decreased(P＜0.05),and the level of IL-10 was significantly increased(P＜0.05);the percentages of Th17 cells in peripheral blood were significantly decreased(P＜0.05),the percentages of Treg cells were significantly increased(P＜0.05),and the Th17/Treg ratios were significantly decreased(P＜0.05).Compared with XBJ-L group,the neurological function injury score of the mice in XBJ-H group was significantly decreased(P＜0.05),the EB level in brain tissue was significantly decreased(P＜0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P＜0.05);the serum levels of IL-17 and IL-22 were significantly decreased(P＜0.05),and the level of IL-10 was significantly increased(P＜0.05);the percentage of Th17 cells in peripheral blood was significantly decreased(P＜0.05),the percentage of Treg cells was significantly increased(P＜0.05),and the Th17/Treg ratio was significantly decreased(P＜0.05).Conclusion:Xuebijing injection can improve BBB injury,regulate Th17/Treg balance,and thereby alleviate the neurological functional damage in anti-NMDAR encephalitis.

Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3％)who received NAC(NAC group)and 30(29.7％)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P＞0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0％vs.46.7％,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6％vs.83.3％,P=0.026;45.1％vs.70.0％,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3％vs.33.8％,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P＜0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.

Objective To explore the effects of fecal microbiota transplantation(FMT)on oxalate metabolism and renal protection in rats fed a high oxalate diet.Methods Twenty-four male SD rats were randomly divided into four groups:SC,SC+FMT,OD+PBS and OD+FMT.The SC group was set as the control group and was fed standard rat chow.The OD+PBS group and OD+FMT group were fed a diet containing 5%oxalate.Starting from day 14,the OD+PBS group,OD+FMT group and SC+FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days.The 24-hour urine,feces,and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers.Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin,ACE,and OPN.Results The fecal microbiota transplantation altered the gut microbiota of rats.The gut microbiota of the SC+FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs.Compared to the OD+PBS group,the OD+FMT group exhibited significant reductions in the urinary oxalate,urinary urea,uric acid,urinary creatinine,serum urea nitrogen/creati-nine,and serum uric acid.Furthermore,after FMT treatment,the OD+FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD+PBS group;similar results were obtained from immunohistochemistry.Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut,particularly the oxalate-degrading bacteria represented by Muribaculaceae.The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate,indicating the protective effect of fecal microbiota transplantation on the rat kidneys.

Objective:To examine the prevention effecacy and safety of preprotein convertase subtilisin-kexin 9 (PCSK9) inhibitors in stroke in patients with atherosclerotic cardiovascular disease (ASCVD) at primary and secondary prevention.Methods:PubMed, Embase, Web of Science, Cochrane Library, and Wanfang and CNKI databases were searched for randomized controlled trials comparing evolocumab, alirocumab, tafolecimab or inclisiran (experimental group) with placebo or conventional therapy (control group) in hyperlipidemia and ASCVD from inception to March 2024. Valid data were extracted after screening and applying Cochrane Literature quality assessment tool to assess the literature quality. Efficacy outcome (incidences of stroke and ischemic stroke) and safety outcome (cardiovascular mortality, and incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke) were recorded. Meta analysis of the extracted data was conducted using Stata software to calculate the risk difference ( RD). Results:Twenty articles (21 randomized controlled trials) were included with 62 799 patients. For primary prevention, no significant difference was found between PCSK9 inhibitors and control groups in stroke incidence ( RD=0.000, 95% CI: -0.002-0.003, P=0.905) or ischemic stroke incidence ( RD=0.001, 95% CI: -0.005-0.006, P=0.824); incidence of creatine kinase increased by more than 3 times in the PCSK9 inhibitors group was significantly decreased compared with that in the control group ( RD=-0.005, 95% CI: -0.010-0.000, P=0.039). For secondary prevention, PCSK9 inhibitors group had significantly reduced stroke incidence ( RD=-0.004, 95% CI: -0.006--0.002, P<0.001) and ischemic stroke incidence ( RD=-0.003, 95% CI: -0.005--0.002, P<0.001) compared with control group; no significant differences in cardiovascular mortality, or incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke were noted between the PCSK9 inhibitors group and control group ( P>0.05). Conclusion:PCSK9 inhibitors in primary prevention have no significant effect on stroke or ischemic stroke incidences, but can decrease the incidence of creatine kinase increased by more than 3 times; PCSK9 inhibitors in secondary prevention can reduce stroke and ischemic stroke incidences without increasing complications and thus enjoying certain safety.

Objective:To investigate the effect of "simulated Chinese medicine nursing clinic" teaching on syndrome differentiation ability among nursing students and the teaching effect of this method.Methods:A total of 325 students were randomly divided into conventional teaching group with 163 students (receiving conventional nursing teaching) and real situational teaching group with 162 students (receiving "simulated Chinese medicine nursing nursing clinic" teaching at the same time). A self-made questionnaire for syndrome differentiation-based nursing ability, assessment scores of traditional Chinese medicine nursing theories and skills, and a teaching satisfaction questionnaire were used for evaluation.Results:After intervention, the real situational teaching group (the treatment group and the experience group) had significantly higher socres of syndrome differentiation-based nursing ability (mastery of four diagnostic methods, diagnosis of syndromes, analysis of syndromes, determination of nursing principles, and development of nursing regimens) than the conventional teaching group (the treatment group and the conventional teaching group: 8.97±1.00/8.47±1.20/8.33±1.06/8.30±1.26/7.89±1.13 and 7.96±1.14/7.29±1.36/7.14±1.18/7.39±1.30/7.26±1.18, P<0.05; the experience group and the conventional teaching group: 8.39±1.10/8.17±1.15/8.07±1.06/7.97±1.26/7.73±1.38 and 7.96±1.14/7.29±1.36/7.14±1.18/7.39±1.30/7.26±1.18, P<0.05). The real situational teaching group had a significantly higher overall degree of satisfaction with teaching than the conventional teaching group [160 (97.6%) and 150 (92.0%), P<0.05]. Conclusions:The "simulated Chinese medicine nursing clinic" teaching program effectively enhances the thinking of syndrome differientiation and related abilities for nursing, improves the learning effect of traditional Chinese medicine nursing theories and skills, and increases the learning interest in traditional Chinese medicine nursing among nursing students.

Objective:To discuss the effect of Xuebijing on brain tissue damage and immune imbalance of helper T lymphocyte 17(Th17)/regulatory T lymphocyte(Treg)in cerebrospinal fluid(CSF)of the N-methyl-D-aspartate(NMDA)receptor encephalitis model mice,and to clarify its therapeutic effect.Methods:Sixty healthy male C57BL/6J mice were randomly divided into control group,model group,low dose of Xuebijing group,and high dose of Xuebijing group,and there were 15 mice in each group.Except for control group,the mice in the other three groups were injected with the antigen combined with immunostimulation to establish the NMDA receptor encephalitis models.The mice in low and high doses of Xuebijing groups were injected intraperitoneally with 5 and 10 mL·kg-1 of Xuebijing injection,respectively.HE staining was used to observe the pathomorphology of brain tissue of the mice in various groups;TUNEL assay was used to detect the apoptotic rates of the neurons in hippocampus CA1 region of brain tissue of the mice in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of interleukin(IL)-6,IL-10,IL-17,and transforming growth factor β(TGF-β)in serum of the mice in various groups;flow cytometry was used to detect the percentages of Th17 and Treg cells in CSF of the mice in various groups;Western blotting method was used to detect the expression levels of retinoic acid-related orphan receptor γt(RORγt),forkhead box protein 3(Foxp3),IL-10,and IL-17 proteins in brain tissue of the mice in various groups;immunohistochemistry method was used to detect the rates of IL-17 and Foxp3 positive cells in brain tissue of the mice in various groups.Results:The HE staining results showed that the hippocampus CA1 region of brain tissue of the mice in control group had a clear structure without obvious lesions;compared with control group,the mice in model group showed partial pyramidal cell shrinkage,elongation of apical dendrites,loss of a few neurons,and sparse tissue in the hippocampus CA1 region of brain tissue;compared with model group,the mice in low and high doses of Xuebijing groups showed that the damage of the cells in the hippocampus CA1 region of brain tissue was decreased,and the morphological recovery,more orderly arrangement,and more significant improvement could be seen in hippocampus CA1 region of the mice in high dose of Xuebijing group.The TUNEL assay results showed that compared with control group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in model group was significantly increased(P<0.05);compared with model group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05);compared with low dose of Xuebijing group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05).The ELISA results showed that compared with control group,the levels of IL-6 and IL-17 in serum of the mice in model group were significantly increased(P<0.05),while the levels of IL-10 and TGF-β were significantly decreased(P<0.05);compared with model group,the levels of IL-6 and IL-17 in serum of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05);compared with low dose of Xuebijing group,the levels of IL-6 and IL-17 in serum of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in model group was significantly increased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly decreased(P<0.05);compared with model group,the percentages of CD4+IL-17A+Th17 cells in CSF of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05);compared with low dose of Xuebijing group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in model group were significantly increased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly decreased(P<0.05);compared with model group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05);compared with low dose of Xuebijing group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05).The immunohistochemistry results showed that compared with control group,the rate of IL-17 positive cells in brain tissue of the mice in model group was significantly increased(P<0.05),while the rate of Foxp3 positive cells was significantly decreased(P<0.05);compared with model group,the rates of IL-17 positive cells in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the rates of Foxp3 positive cells were significantly increased(P<0.05);compared with low dose of Xuebijing group,the rate of IL-17 positive cells in brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the rate of Foxp3 positive cells was significantly increased(P<0.05).Conclusion:Xuebijing can effectively ameliorate the brain tissue injury,regulate the cytokine levels,and intervene in immune imbalance of Th17/Treg in the mice with anti-NMDA receptor encephalitis.

Objective:To explore the effect of fecal microbiota transplantation (FMT) on the formation of renal calcium oxalate crystals in SD rats induced by oxalate mixed diet.Methods:Six male guinea pigs were fed with standard guinea pig chow for 1 month and then given a 5% oxalate diet for 14 d. The guinea pigs on the standard chow were labeled as the standard chow guinea pig (GSC group) and those on the high oxalate diet for 14 d were labeled as the guinea pig group on the high oxalate diet (GOD group). The feces of guinea pigs in the GSC and GOD groups were collected using metabolic cages. Twenty-four male SD rats were randomly divided into standard chow (SC) group, oxalate diet(OD)+ phosphate buffered saline gavage group (OD+ PBS group), OD+ FMT group and SC+ FMT group. Among them, the SC group and SC+ FMT group were fed with standard chow. The OD+ PBS group and OD+ FMT group were fed with 5% oxalate content chow. The OD+ FMT and SC+ FMT groups were given GOD group guinea pig fecal filtrate gavage for 7 days. The 24 h urine and feces of rats in each group were collected, and the intestinal microbiota of rats and guinea pigs were detected by 16sRNA detection. The urinary oxalate excretion was detected by high performance liquid chromatography. The rats and kidneys were weighed and the renal index was calculated. HE staining was used to observe the histological morphological changes of rat kidney tissue, the calcium oxalate crystal deposition in renal tissues was detected by Pizzolato staining.Results:The relative abundance of bacteria from a total of 11 families, including Muribaculaceae family and Bifidobacteriaceae family, was significantly increased in the intestinal tract of guinea pigs (GOD) from the high oxalate diet group compared to guinea pigs (GSC) from the standard chow group. The microbial diversity of the intestinal microbiota of the rats in the OD+ PBS group was reduced compared to the SC group, and the microbial diversity of the intestinal microbiota of the rats in the OD+ FMT group was restored compared to the OD+ PBS group. When given a standard chow, the intestinal microbiota of rats receiving FMT deviated from that of normal rats and was more similar to that of guinea pigs fed a high oxalate diet. In the OD+ FMT group, bacteria from a total of 18 families, including Muribaculaceae family, Erysipelotrichaceae family and Bifidobacteriaceae family, were significantly enriched, and FMT activated the intestinal microbial network represented by bacteria from Muribaculaceae family. The renal index of rats in the OD+ PBS group was significantly increased compared to the SC group (7.63±0.67 vs. 6.12±0.53, P<0.05), whereas the renal index of rats in the OD+ FMT group was significantly decreased in comparison to the OD+ PBS group (6.53±0.64 vs. 7.63±0.67, P<0.05). Urinary oxalate excretion of rats in the SC group, the OD+ PBS group, and the OD+ FMT group were (0.61±0.05), (0.89±0.04) and (0.72±0.04) μmol/ml, respectively. In the rats of the SC group no calcium oxalate crystals were seen in the kidney (0 score) and more calcium oxalate crystals were detected in the OD+ PBS group (4.83±0.41 score). The OD+ FMT group showed significantly lower calcium oxalate crystallization scores (3.17 ± 0.75 score, P<0.01) compared to the OD+ PBS group. Conclusions:FMT activated the microbial network represented by bacteria from the family Muribaculaceae in the rat intestine, significantly reduced urinary oxalate excretion and renal calcium oxalate crystal deposition in rats on a high oxalate diet.

A case of syphilis-related membranous proliferative glomerulonephritis is reported, presenting with fever, rash, generalized lymphadenopathy, and peripheral hypocytosis as the initial symptoms. The patient was admitted to the hospital and underwent various examinations to rule out lymphoma and other diseases. Subsequently, the patient developed edema with proteinuria. The toluidine red unheated serum test (TRUST) was 1∶4 (+) and the treponema pallidum particle agglutination (TPPA) test was >1∶160 (+). The pathological results of renal biopsy revealed membranous proliferative glomerulonephritis. The diagnosis of the patient was considered syphilitic nephropathy. Treatment with penicillin resulted in improvement of the condition. The coexistence of syphilitic nephropathy and membranous proliferative glomerulonephritis is rare and should be given careful attention in clinical practice. Antisyphilitic treatment improves the prognosis.

Objective:To evaluate the preventive role and safety of evolocumab and alirocumab in ischemic stroke in hyperlipidemia and atherosclerotic high-risk cardiovascular patients.Methods:PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases were searched for randomized controlled trials (RCTs) comparing evolocumab or alirocumab (experimental group) with placebo or usual care (control group) in hyperlipidemia and atherosclerotic high-risk cardiovascular patients from database inception to March 2023. References were screened and data were extracted according to the preset inclusion and exclusion criteria; incidence of ischemic stroke was as the efficacy index, and incidences of cardiovascular death, cognitive impairment, aminotransferase increased for more than 3 times and creatine kinase increased for more than 3 times were as the safety index. Cochrane Reviewer Handbook 2.0 was used to evaluate the RCTs literature quality. Meta analysis was performed using Stata software.Results:A total of 11 articles were included, including 12 studies with a total of 53 666 patients. Compared with the control group, the incidence of ischemic stroke in the experimental group was significantly decreased (risk difference [ RD]=-0.004, 95% CI: -0.005--0.002, P<0.001); there were no significant differences in the incidence of cardiovascular death, cognitive impairment, aminotransferase increased for more than 3 times and creatine kinase increased for more than 3 times between the 2 groups ( RD=-0.001, 95% CI: -0.004-0.001, P=0.401; RD=0.000, 95% CI: -0.003-0.002, P=0.638; RD=-0.001, 95% CI: -0.004-0.002, P=0.443; RD=-0.001, 95% CI: -0.003-0.000, P=0.137). Subgroup analysis was performed according to drugs: compared with the control group, the incidence of ischemic stroke was significantly reduced in the evolocumab group and alirocumab group ( RD=-0.004, 95% CI: -0.007--0.001, P=0.006; RD= -0.003, 95% CI: -0.006-0.000, P=0.024); there were no significant differences in incidences of cardiovascular death ( RD=0.001, 95% CI: -0.002-0.004, P=0.619; RD=-0.003, 95% CI: -0.007-0.001, P=0.100), cognitive impairment ( RD=0.001, 95% CI:-0.002-0.004, P=0.463; RD=-0.002, 95% CI: -0.005-0.001, P=0.145), aminotransferase increased for more than 3 times ( RD=0.000, 95% CI: -0.003-0.003, P=0.888; RD=-0.002, 95% CI: -0.007-0.003, P=0.392) or creatine kinase increased for more than 3 times ( RD=0.000, 95% CI: -0.002-0.002, P=0.668; RD=-0.002, 95% CI: -0.005-0.000, P=0.106) between the evolocumab group and alirocumab group. Subgroup analysis was performed according to the medication duration: compared with the control group, no significant differences in incidences of cardiovascular death ( RD=0.000, 95% CI:-0.022-0.022, P=1.000; RD=-0.003, 95% CI: -0.009-0.002, P=0.193; RD=-0.001, 95% CI:-0.004-0.002, P=0.521), cognitive impairment ( RD=-0.003, 95% CI: -0.014-0.008, P=0.569; RD=-0.001, 95% CI: -0.006-0.004, P=0.696; RD=0.000, 95% CI: -0.003-0.002, P=0.735), aminotransferase increased for more than 3 times ( RD=-0.002, 95% CI: -0.016-0.012, P=0.749; RD=-0.002, 95% CI: -0.013-0.010, P=0.773; RD=-0.001, 95% CI: -0.004-0.002, P=0.489) or creatine kinase increased for more than three times ( RD=-0.015, 95% CI: -0.032-0.003, P=0.099; RD= -0.011, 95% CI: -0.025-0.002, P=0.104; RD=0.000, 95% CI: -0.002-0.001, P=0.722) were noted among medication duration<1 year group, medication duration of 1-2 years group and medication duration>2 years group. Conclusion:Both evolocumab and alirocumab can reduce the incidence of ischemic stroke in hyperlipidemia and atherosclerotic high-risk cardiovascular patients, with good safety.

Objective:To investigate the associations between plasma trimethylamine-N-oxide (TMAO) level and premature coronary heart disease (PCHD).Methods:From July 2018 to July 2020, total of 166 patients with suspected coronary heart disease were enrolled from the Heart Center of Shenzhen Bao′an Hospital affiliated to Southern Medical University. According to the coronary imaging results and age of onset, they were divided into young control group ( n=30), PCHD group ( n=49), middle-aged and elderly control group ( n=30) and the middle-aged and elderly coronary heart disease group ( n=57). Plasma TMAO concentration in each group was determined by stable isotope liquid chromatography/mass spectrometry, and the correlation of plasma TMAO level with PCHD and SYNTAX score was analyzed. Results:The plasma TMAO level in PCHD group was significantly higher than that in young control group [(7.54±2.10) μmol/L vs. (4.60±1.89) μmol/L; t=6.73, P?0.001] and middle-aged and elderly coronary heart disease group [(3.90±1.75) μmol/L; t=2.45, P=0.015]. The plasma TMAO level was positively correlated with SYNTAX score in PCHD group ( r=0.66, P?0.001) and in middle-aged and elderly coronary heart disease group ( r=0.27, P=0.042). Multivariate logistic regression analysis showed that plasma TMAO level was an independent risk factor for PCHD ( OR=2.30, P?0.001). Receiver operating characteristic (ROC) curve analysis showed that when the cutoff level of plasma TMAO was 6.08 μmol/L, the sensitivity and specificity for diagnosis of PCHD were 73.5% and 76.7%, respectively. Conclusion:The plasma TMAO level is significantly correlated with PCHD and had certain predictive value for PCHD.