BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

Objective:To investigate the possible mechanism of treadmill exercise(TR)in improving cognitive function of rats with chronic unpredictable mild stress(CUMS)by detecting pathological changes and the expression of sigma-1 receptor(SIR),endoplasmic reticulum stress-related proteins in hippocampus.Methods:30 SD rats were ran-domly allocated into control group(n=10),CUMS group(n=10)and CUMS exercise group(CUMS+TR,n=10).Subsequently,depressive model was established in rats of CUMS group and CUMS+TR group,meanwhile,CUMS+TR group rats were subjected to 4 weeks of moderate intensity treadmill exercise(20 m/min).After the CUMS and tread-mill exercise,the eight-arm radial maze test(RAM)was carried out to evaluate the learning-memory functions.Subse-quently,the pathological changes of neurons in the hippocampus of rats were measured by HE staining,the protein expression of the GRP78,IRE1,XBP1,CHOP,caspase-3 and SIR in the hippocampus were measured by Western blot.Results:Compared with the control group,the time of finishing the eight-arm radial maze prolonged and the num-ber of total memory errors increased(P＜0.05)in the RAM of the CUMS group rats.The morphology and structure of neurons in the hippocampus of CUMS group rats showed obvious pathological changes,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 significantly increased and SIR protein expression decreased(P＜0.05)in hippocampus in the CUMS group compared with the control group rats.4-week treadmill exercise significantly im-prove the learning and memory ability and pathological changes of neurons in hippocampus of CUMS+TR group rats.Compared with CUMS group rats,the protein expression levels of GRP78,IRE1,XBP1,CHOP and caspase-3 signifi-cantly decreased,the SIR expression in hippocampus significantly increased in the CUMS+TR group rats(P＜0.05).Conclusion:Treadmill exercise can improve cognitive impairment in CUMS rats,and its mechanism may be related to the up-regulation of SIR expression and the inhibition of ERS-mediated apoptosis pathway in hippocampus.

Background and objective Synchronous multiple primary lung cancer (sMPLC) is a sparse disease in the past, but there has been a gradual increase in the morbidity of sMPLC recently. However, studies on large sample have never been undertaken. hTe purpose of this study is to investigate the diagnosis, treatment and prognosis of sMPLC through analyzing the clinical data, and provide supports for the management of sMPLC. Methods According to Martini-Melamed criteria, 357 patients were diagnosed sMPLC. hTe pathological staging is on the basis of the 8th edition tumor-node-metastasis (TNM) staging from International Association for the Study of Lung Cancer (IASLC). Results There were 269 patients with double primary lung cancer, 65 patients with triple primary lung cancer and 23 patients with four or more primary lung cancer. Lesions (68.55%, 571/833) were frequently in upper lobe, especially the right upper lobe. Adenocarcinoma (95.56%, 796/833) was the mainly pathological type, followed by squamous cell carcinoma (2.40%, 20/833). hTe acinar predominant subtype was the main part (70.81%, 313/442) of the all adenocarcinoma specimens. Most of the lesions (68.35%, 244/357) were stage Ib or low. Among the initial lesion and the following lesions ,patients who had the same pathological type (92.72%, 331/357) were more than the different (7.28%, 26/357), of which adenocarcinoma-adenocarcinoma occupied the major pro-portion (99.40%, 329/331). hTe 3-year overall survival (OS) and 5-year overall survival were respective 91.93%and 84.37%. Multivariate analysis found that smoking history (P=0.012), the diameter of the maximum lesion (P=0.027), lymph node me-tastasis (P=0.015) and pleural invasion (P<0.001) were the independent risk factors for prognosis. Conclusion Tumours in patients with sMPLC are more frequently in the right upper lobe. Adenocarcinoma was the mainly pathological type. Smoking history, the diameter of the maximum lesion, lymph node metastasis and pleural invasion were the independent risk factors for prognosis. Early diagnosis and active operation can obtain better prognosis.

We investigated the distribution characteristics of Yersinia enterocolitica in Ningxia ,China .In accordance with the requirements of the National Yersinia enterocolitica Disease Monitoring Scheme ,Y .enterocolitica were isolated from differ‐ent kinds of specimens collected in Ningxia in 2008 to 2013 .Then they were serotyped and detected for virulence gene and ana‐lyzed the pulsed‐field gel electrophoresis (PFGE) in Chinese CDC .It was found that 173 strains were isolated from various types of 9 643 specimens ,and the detection rate was 1 .79% .There were statistical differences among detection rates in differ‐ent years and in different specimens (P<0 .01) .Pathogenic serotypes O∶3 and O∶9 carried ail gene and ystA gene were de‐tected from specimens of pigs and diarrhea patient .Non‐pathogenic serotypes O∶5 and O∶8 and non‐typeable strains didn't carry ail gene and ystA gene ,and also can't be detected from swine ,cattle ,sheep ,chickens and dogs .In conclusion ,Y .en‐terocolitica was widely distributed in Ningxia and pigs were the dominant animal host .In all pathogenic serotypes ,the highest proportion was O∶3 following by O∶9 .It was no time and regional difference in the distribution of that in Ningxia ,China .

BACKGROUND:At present, biological agent-involved immunologic induction therapy gradual y became a key component in immunosuppression therapy of kidney transplantation. It can effectively prevent acute rejection and avoid the appearance of complications. OBJECTIVE:To evaluate the effect of different biological agents on immune state and functional status of transplanted kidney in immunologic induction therapy. METHODS:Clinical data of 110 recipients with kidney transplantation were retrospectively analyzed. In accordance with the conditions of immunologic induction therapy, recipients in the monoclonal antibody group (n=35) received basiliximab. Recipients in the polyclonal antibody group (n=43) underwent rabbit anti-human antithymocyteglobulin. Recipients in the control group (n=32) did not receive immunologic induction therapy. Absolute value of lymphocytes and the number of CD4+T lymphocyte subsets in peripheral blood were comparatively analyzed among three groups at 1, 4 and 12 weeks after kidney transplantation. Functional status of the transplanted kidney and complications of infection were evaluated at 12 weeks after transplantation.RESULTS AND CONCLUSION:The incidence of acute rejection was lower in the monoclonal antibody group and polyclonal antibody group than in the control group (P<0.05). The incidence of infectious complications was higher in the polyclonal antibody group than in the monoclonal antibody group and control group (P<0.05). The absolute value of lymphocytes was lower in the monoclonal antibody group and polyclonal antibody group at 1, 4 and 12 weeks after transplantation than in the control group (P<0.05). The number of CD4+T lymphocyte subsets in peripheral blood was lower in the polyclonal antibody group than in the monoclonal antibody group and control group at 1, 4 and 12 weeks after transplantation (P<0.05). These results suggested that biological agents participate in immunologic induction therapy of kidney transplantation, can effectively suppress the functional status of activated T lymphocytes, and decrease the occurrence of early acute rejection of the transplanted kidney. However, the incidence of infectious complications was higher after the use of rabbit anti-human antithymocyteglobulin.

Objective Toevaluateefficacyandsafetyoftwodifferentbiologicalsinimmunologic inductiontherapyonrenaltransplantrecipients.Methods Clinicaldataof78renaltransplantrecipientswho received biological immunologic induction therapy in Department of Urology of the 452nd Hospital of Chinese People's Liberation Army from June 2008 to April 2013,were retrospectively analyzed. According to different biological immunologic induction therapy,the recipients were divided into two groups,monoclonal antibody group (group A,n=35,received treatment of basiliximab)and polyclonal antibody group [group B,n=43, received treatment of antithymocyte globulin (ATG)]. And the other recipients who didn't receive immunologic induction therapy in the hospital during the corresponding period were chosen as control group (group C,n=32). The survival rates of recipient and kidney in 3 groups at 12th weeks after transplantation were analyzed.The levels of serum creatinine (Scr)of recipients in 3 groups were monitored at 7,14,30,60 d after transplantation. The occurrence rates of complications including acute rejection,delayed graft function and infectionwerecomparedamong3groups.Results At12thweeksaftertransplantation,thesurvivalratesof recipient and kidney in 3 groups were 100% and 100% in group A,97.7% and 97.7% in group B,100%and 96.9% in group C. There was no significant difference among 3 groups (all in P>0.05 ). Compared with group C,the Scr levels in group A and B decreased significantly at 7,14 d after transplantation (all in P<0.05 ). Compared with group C,the incidence rates of acute rejection decreased in group A and B(all in P<0.05 ). There was no significant difference in the incidence rates of delayed graft function among 3 groups (all in P>0.05 ). The incidence rate of infection in group B was significantly higher than those in group A and C (allinP<0.05).Conclusions Immunologicinductiontherapyissafeandeffectiveintheapplicationon renal transplant recipients.

Objective To observe the effects of rosuvastatin on the homocysteine (Hcy)-induced expression of matrix metalloproteinase 2 (MMP 2) and cell migration in rat vascular smooth muscle cells (VSMCs), and to explore the possible mechanism of Hcy-induced atherosclerosis and the role of statins in reversing atherosclerosis. Methods In one cell culture plate, the cultured rat VSMCs were incubated with different concentrations of Hcy (0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L) in vitro for 24 h, 48 h and 72 h. And in another cell culture plate, the different concentrations of rosuvastatin (10-9, 10-8, 10-7, 10-6, 10-5 mol/L and 0 mol/L) were added to the cultured rat VSMCs (while the concentration of Hcy was 1000 μmol/L). The MMP 2 expression and enzyme activity were determined by gelatin zymography and Western blotting. The effects of Hcy and rosuvastatin on cell migration and invasiveness of VSMCs were observed. Results Hcy (50-5000 μmol/L) increased the protein expression, and Hcy (50-1000 μmol/L) increased enzyme activity of MMP 2 significantly. But Hcy (5000 μmol/L) inhibited activity of MMP 2 (F=9.31, 6.44 and 5.97, all P＜0.05). Rosuvastatin (10-9-10-5 mol/L) inhibited Hcy-induced expression and enzyme activity increasing of MMP 2. The counts of cell migration of VSMCs were 18.32±2.17, 32.68±4.34, 44.75±4.08, 61.39±5.21, 79.74±5.54 and 90.78±5.83, while the concentration of Hcy was 0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L respectively (F=5.31, P＜0.05). The counts of cell migration of VSMCs were 79.74±5.54, 62.53±6.41, 48.37±5.66, 31.41±4.79, 19.27±3.62 and 11.17±2.33, while the concentration of rosuvastatin was 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L respectively (F=4.99, P＜0.05). Rosuvastatin could decrease the stimulation of Hcy-induced migration of VSMCs. Conclusions Hcy can influence the MMP 2 protein expression/activity in VSMCs, and rosuvastatin can inhibit augmentation of Hcy-induced MMP 2 expression/activity and migration of VSMCs. It may be one of the multiple-effects of rosuvastatin reducing atherosclerosis.

AIM: To study the possibility that yellow wine improves the pathological changes of atherosclerosis in vivo. METHODS: Six weeks old LDL receptor knockout mice (n=48) on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. The animals were randomly divided into yellow wine group, red wine group, ethanol group and control group (n=12 in each group) and were sacrificed after 14 weeks. The levels of plasma lipids and homocysteine in serum were examined. The morphological changes of aorta artery and the atherosclerosis of aorta sinus were observed under microscope. The expression and activation of matrix metalloproteinase-2 (MMP-2) were determined by the method of immunohistochemistry. RESULTS: No significant difference of plasma total cholesterol, triglyceride or high density lipoprotein cholesterol among groups was observed. Plasma homocysteine was significantly decreased in yellow wine group as compared to other three groups (P<0.01). Compared to ethanol and control groups, use of yellow wine and red wine significantly reduced the atherosclerosis lesion area (P<0.01). However, no significant discrepancy between the yellow wine group and red wine group was found. Compared to control group, the expression of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 26.3%, 27.6% (P<0.01) and 5.7% (P>0.05), respectively. The activity of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 31.7%, 32.5% (P<0.01) and 6.7% (P>0.05), respectively. CONCLUSION: Yellow wine and red wine inhibit the expression of MMP-2 and improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.