Objective To explore the feasibility of applying equivalence testing to evaluate the similarity between reference standards and test samples in the biological activity assessment of glucagon like peptide-1(GLP-1) receptor agonist drugs,so as to improve the determination standard of biological activity of various products.Methods Historical release biological activity data from 25 batches of products were collected,and the parameter estimates and standard errors of a four-parameter logistic model were obtained.The slope ratio of test samples to reference standards and dynamic range ratio(ratio of the difference between upper and lower asymptotes of test samples to that of reference standards) were selected as similarity evaluation metrics,and tolerance interval method was used to set equivalence margins for these metrics.Subsequently,biological activity data from 86 additional batches of GLP-1 receptor agonist drugs(57 reference standards with similar biological behaviors to those of test samples and 29 reference standards with non-similar biological behaviors) were analyzed using equivalence testing to determine similarity.For comparison,an F-test was also performed to assess parallelism.The agreement between the two methods was evaluated using Kappa test.Results The equivalence intervals for the slope ratio and dynamic range ratio were 0.64-1.56 and 0.87-1.15,respectively.For the 86 batches,equivalence testing correctly identified 95%(54/57) of truly similar samples as similar and 86%(25/29) of non-similar samples as non-similar.In contrast,the F-test correctly identified 88%(50/57) of parallel samples as parallel and 72%(21/29) of non-parallel samples as non-parallel.Kappa test indicated moderate agreement between the two methods(Kappa=0.417).Conclusion Equivalence testing is suitable for evaluating similarity in the biological activity of GLP-1 receptor agonist drugs and outperforms the F-test in similarity assessment.

Objective To analyze the correlation of inflammatory markers C-reactive proten(CRP),serum amyloid protein A(SAA),interleukin-6(IL-6)levels and subjective sleep characteristics in patients with first-episode acute cerebral infarction.Methods A total of 113 patients with first-episode cerebral infarction admitted to the Department of Neurology,the People's Hospital of Fuyang from March 2022 to April 2023 were prospectively and continuously selected as subjects.According to the Pittsburgh sleep quality index(PSQI),they were divided into insomnia group(PSQI＞7 points)and non-insomnia group(PSQI ≤7 points).General demo-graphic data and differences in CRP,SAA,IL-6 levels,Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD)scores were compared between the two groups.Partial correlation analysis was used to analyze the correlation between three serum markers and PSQI effect factors.Results There were no significant differences in age,gender,baseline NIHSS score and mRS score between the two groups(P＞0.05).HAMD scores(z=-3.993,P＜0.001),HAMA scores(z=-3.806,P＜0.001),CRP,IL-6,SAA(P＜0.001)in insomnia group were significantly higher than those in non-insomnia group.The history of hyperlipidemia between the two groups was statistically significant(z=5.913,P=0.015).Multivariate Logisitic regression analysis showed that CRP(OR=1.55,P＜0.01),HAMD scores,HAMA scores and hyperlipidemia were independent risk factors for chronic insomnia in patients with first-episode cerebral infarction,and HAMD scores had a greater effect than HAMA scores(OR:1.10 vs 1.04).Partial correlation analysis showed that IL-6 and CRP levels were significantly correlated with the total score of PSQI(P＜0.05),while SAA was not significantly correla-ted with the total score of PSQI(P＞0.05).IL-6 level was positively correlated with sleep quality(r=0.231)sleep efficiency(r=0.322)and sleep duration(r=0.221).SAA level was positively correlated with sleep efficiency(r=0.242),while CRP level was posi-tively correlated with sleep latency(r=0.194),sleep duration(r=0.247)and sleep efficiency(r=0.225).Conclusion The inflam-matory markers CRP,IL-6 and SAA levels were elevated in the patients with first-episode cerebral infarction accompanied by insomnia,which were correlated with the severity of insomnia.The correlation between CRP and IL-6 levels and sleep characteristics was consistent with each other.

Lipopolysaccharide(LPS),lipteichoic acid(LTA) and zymosan can be recognized by Toll-like receptors (TLRs) ex-pressing in the inflammatory cells membrane,such as macrophages,monocytes and endothelial cells,and then induce the secretion of pyrogenic cytokines followed by triggering inflammatory reaction. The signaling pathway mechanisms were summarized, including the extracellular signaling cascades from pyrogens to individual TLRs,and intracellular signaling cascades from TLRs to nucleus.

Objective To explore the possible mechanism of apoptosis induced by SARS-CoV-2 targeting cyclophilin A(CypA)/CD147 receptor pathway.Methods The pEncmv-SARS-CoV-2 S-3xflag recombinant plasmid was constructed and transfected into H9C2 cells.Apoptosis was analyzed by TUNEL assay,flow cytometry and DNA ladder.The interaction between CD147 and SARS-CoV-2 S protein was verified by CoIP.The expressions of apoptosis-related proteins were detected by Western blotting.Results Compared with the control group,TUNEL assay and flow cytometry showed that apoptosis was significantly increased in transfection group(P＜0.05),and DNA ladder analysis showed that DNA degradation was obvious.The expression levels of Caspase12 and DR3 were significantly increased(P＜0.001),the expression level of FAS was slightly increased(P＜0.01),while the expression levels of TRF1 and DR4 were decreased(P＜0.01).Conclusion SARS-CoV-2 S protein targets CypA/CD147 receptor to invade host cells,activate endoplasmic network pathway(Caspase12)and death receptor pathway(DR3,FAS),and induce apoptosis of cardiomyocytes through endogenous and exogenous apoptotic pathways.

Objective: To explore the hemorrhagic transformation(HT) and its effect on prognosis in patients with acute ischemic stroke(AIS) after mechanical thrombectomy(MT). Methods: A total of 114 patients with AIS received MT were enrolled. The modified Rankin Scale was used to evaluate the clinical outcome at 90 days of onset(0-2 points were good prognosis; 3-6 points were poor prognosis). The patients were divided into HT group(n=25) and non-HT group(n=89) according to their HT conditions. Binomial Logistic regression analysis was performed to determine the vascular risk factors of HT after MT and the effect of HT on prognosis. Results: Among 114 patients, there were 25 cases of HT and 89 cases of non HT. The proportion of patients with diabetes in HT group was significantly higher than that in non-HT group. The NIHSS score of HT group at discharge was significantly higher than that in non-HT group. The proportion with good prognosis at 90 days in HT group was significantly lower than that in non-HT group(allP<0.05). Binomial Logistic regression analysis showed that diabetes, high levels of cholesterol and smoking were the major vascular risk factors for HT after thrombectomy(allP<0.05). HT was an important factor affecting the poor prognosis after arterial thrombectomy(P=0.026). Conclusion Diabetes, high levels of cholesterol and smoking are the main risk factors of HT after MT for AIS. HT is an independent risk factor for poor prognosis after MT.