The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe ^-/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Objective: To analyze the trend of lung cancer incidence rate among rural residents in Feicheng city between the years 2000 and 2012,and predict the incidence rate between the years 2013 and 2018,and subsequently provide baseline data for lung can-cer control and prevention.Methods:With the cancer registration data in Feicheng rural areas,the time trend of lung cancer inci-dence rate and the annual percentage change(APC)were calculated by the Joinpoint model,while the incidence of lung cancer from 2013 to 2018 were predicted by the ARIMA(p,d,q)model.Results:A total of 3,908 new cases of lung cancer were diagnosed be-tween 2000 to 2012.The incidence rate was 40.77/105,the age-specific cancer incidence rate in the Chinese population(ASRC)and world population(ASRW)were 32.95/105 and 32.97/105,respectively.The incidence was 2.14 times higher among males than females (P<0.001).The incidence of lung cancer which apparently rose from 25.13/105to 64.92/105 with an APC value of 9.74%(P<0.001),was increasing every year.The change in the trend of lung cancer with respect to age could be divided into three segments,the incidence rate in the 0 to 59 years group showed a rapid upward trend(APC=113.38,P<0.001),which was lower in the 60 to 79 years group (APC=20.39,P<0.05)and began to decline in the 80 years or older group(APC=-21.20,P>0.05).The incidence of lung cancer was also observed to be increasing yearly from 2013 to 2018,and with an average annual growth rate of 4.92%,was predicted to reach 87.92/105 in 2018.Conclusions:The occurrence of lung cancer was closely related to population aging,unhealthy habits,and environmental risk factors.Due to the increasing aging population,the incidence of lung cancer will continue to increase.In order to formulate specif-ic strategies,the control and prevention of lung cancer must be based on its incidence features.

Objective To observe the clinical efficacy of electroacupuncture at cervical Jiaji (EX-B2) points plus behavioral intervention in treating cervical spondylosis. Method The cervical spondylosis patients were randomized into two groups at a ratio of 3:1, 90 cases in the electroacupuncture group and 30 cases in the medication group. The patients who received electroacupuncture were also given cupping and behavioral intervention (raising head for 1 min every 20-30 min and correcting sleep habits). The clinical efficacy was evaluated according to the symptoms and body signs assessment scale. Result Respectively after 4-week, 8-week, 4-month and 6-month treatments, the clinical control rate, markedly control rate and total effective rate in the electroacupuncture group were significantly higher than that in the medication group. Conclusion Electroacupuncture at Jiaji points plus behavioral intervention is an effective solution to prevent and treat cervical spondylosis.

Objective To study the protective effects of choline on myocardial ischemia rat heart and its potential mecha -nisms .Methods Ischemia hypoxia environment was simulated with low value of pH (pH 6 .8) and lack of oxygen .Calcium currents were recorded by whole cell patch under the voltage clamp configuration .The alternations in[Ca2 + ]induced by KCl was detected by laser scanning confocal microscope in ventricular myocytes ,then disccuss the effects of choline on calcium and calcium store in cells . Results The normalized peak currents of ICa-L in ventricular myocytes were larger in pH 6 .8 group than those in pH 7 .4 group , which can be attenuated by choline .The(Ca2 + )i induced by KCl in ventricular myocytes were significantly increased in pH 6 .8 Ty-rode solution and its increasing can be suppressed by choline .4-DAMP can inhibit the suppressing effect of choline .Conclusion The possible mechanism of M 3 receptor involved in the protection of ischemic myocardium by inhibiting myocardial cells in ICa-L ,in-hibiting intracellular calcium overload .

Our previous work found that DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl]quinoline) was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II) (CDDP)-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU)-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.

Objective To study the clinical characteristics and to summarize our experience in the diagnosis and treatment of ectopic splenic autotransplantation (ESAP) many years after splenic rupture and splenectomy.Methods The clinical data of 15 patients with ESAP who were treated in the People's Hospital of Zhengzhou from January 1998 to January 2013 were retrospectively analyzed.Results Of the 15 patients,2 patients presented with intestinal obstruction due to the ectopic splenic tissues and required partial resection of small intestine.In 5 patients,the ectopic splenic tissues were in the greater omentum which required resection of part or the whole of the greater omentum.In 4 patients,the ectopic splenic tissues were in the mesentery which required partial or total resection of the tissues.The ectopic tissues were in the pelvis in 3 patients and resection of the left fallopian tube was carried out in 2 patients and resection of the pelvic tissues in 1 patient.In 1 patient the diagnosis was made under laparoscopic biopsy,thus avoiding open surgery.Three patients had multiple implanted sites for these ectopic splenic tissues.Conclusions ESAP is an uncommon disease and it has no clinical characteristics.It is easy to confuse the condition with metastatic deposits.A diagnosis could be made only by combining the history with magnetic resonance imaging,or 99mTc study of red blood cells,or laparoscopic exploration and biopsy.

Objective To investigate the state of hospital nursing assistants occupational protection knowledge and its relative factors .Methods One hundred nursing assistants in a three general hospital were investigated by using self-designed questionnaire , their knowledge of occupational protection and its effect factors were analyzed.Results The total score of occupational protection knowledge was (31.87 ±0.244), with range of the correct item rated from 71.13% to 100%.Correlation analysis showed that work years significantly relative to total protection knowledge score (r =0.358,P <0.05).The physical and chemical protection knowledge score of trained person were higher than the untrained person , the differences were statistically significant (Z=-2.314,-2.00, respectively; P<0.05).Conclusions Scores of occupational protection knowledge among nursing assistants still need to improve , and the occupational standards of nursing assistants also necessary to establish .So according nursing assistants work experiences and situations to emphasize their specialize training are very necessary in the future .