A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC50 values at micromolar range. Compounds I1 (IC50 value of 0.086 μmol · L(-1)) and I2 (IC50 value of 0.080 μmol · L(-1)) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC50 value of 0.094 μmol · L(-1)). Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.

A series of novel 4-substituted-3-nitrobenzamide derivatives were designed and synthesized. The structures of the target compounds were confirmed with 1H NMR, 13C NMR, MS and element analysis. Anti-tumor activities against HCT-116, MDA-MB435 and HL-60 cell lines in vitro were evaluated by SRB assay. The results indicated most of the target compounds exhibited potent anti-tumor activity. Compound 4a showed the most potent inhibitory activities against three cancer cell lines with the GI50 values of 1.904-2.111 micromol x L(-1). Compounds 4g, 41-4n exhibited more potent inhibitory activities against MDA-MB435 and HL-60 cell lines with the GI50 values of 1.008-3.586 micromol x L(-1) and 1.993-3.778 micromol x L(-1), respectively. The structure-activity relationship of these compounds is discussed preliminarily.

Objective:To explore the effect of chemotherapy administration sequence combined with programmed cell death protein-1(PD-1)monoclonal antibody on the efficacy and immune-related adverse events(irAEs)in patients with advanced non-small cell lung cancer(NSCLC).Methods:The clinical data of 110 patients with advanced NSCLC treated at The First Affiliated Hospital of Zhengzhou University between November 2019 and January 2022 were retrospectively collected.The factors influencing irAEs were analyzed by univariate and multivariate Logistic regression analyses,while those influencing curative effect were analyzed by Kaplan-Meier curve analysis,Log-rank test,and univariate and multivariate Cox regression analyses.Results:Treatment with PD-1 monoclonal antibody after 2 days of chemotherapy(sequential treatment group,n=36)significantly prolonged progression-free survival(PFS)compared with PD-1 monoclonal antibody admin-istration on the same day of chemotherapy(simultaneous treatment group,n=74)(17.2 months vs.11.3 months,respectively;P＜0.05).The disease control rate(DCR)was better in the sequential treatment group than in the simultaneous treatment group(94.4％vs.79.7％,re-spectively;P=0.045),while the objective response rate(ORR)did not differ significantly(69.4％vs.51.4％,respectively;P=0.072).The Cox re-gression analysis showed that cytokerat in 19 fragment(Cyfra21-1)and d-dimer(D-dimer)affected the efficacy of combination therapy(P＜0.05).The Logistic regression analysis showed that age and lactic dehydrogenase(LDH)influenced the occurrence of irAEs(P＜0.05),while the administration sequence did not significantly affect the occurrence of irAEs(P=0.130).Conclusions:Administration sequence influences the efficacy of combination therapy,and patients with advanced NSCLC who receive sequential therapy may experience better efficacy.Age and LDH are negatively correlated with the occurrence of irAEs.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

OBJECTIVE: This study aimed to investigate the expression and clinical significance of proline-rich tyrosine kinase 2 (Pyk2) and phospho-protein kinase B (p-AKT) in tongue squamous cell carcinoma (TSCC) and adjacent nontumor tissues. METHODS: The Pyk2 and p-AKT protein levels were detected via immunohistochemistry in 45 cases of TSCC tissues and 30 cases of adjacent nontumor tissues. The relationships of the two protein levels and clinicopathological characteristics were also analyzed. RESULTS: Pyk2 and p-AKT levels were significantly higher in the TSCC tissues than in the adjacent nontumor tissues (P<0.05). Nontumor tissues showed poor or no expression. The expression levels of the two proteins were positively correlated (γs=0.412). The expression of Pyk2 was associated with histopathological differentiation type, regional lymph node metastasis, and TNM staging (P<0.05), but not with age and gender. The expression of p-AKT was only related to histopathological differentiation types (P<0.05). CONCLUSIONS The abnormal expression of Pyk2 and p-AKT proteins might be closely related to the development and progression of TSCC. Joint detection can be used as an indicator to estimate the degree of TSCC.
Carcinoma, Squamous Cell ; metabolism ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Prognosis ; Proto-Oncogene Proteins c-akt ; metabolism ; Tongue Neoplasms ; metabolism