Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative dis-eases.

Objective Zinc sulfate has anti inflammatory action in many animal models, however, the effects of zinc in colitis remained uncertain. The present study was to evaluate the role of zinc sulfate in experimental colitis and probe into its underlying mechanisms. Methods Colitis was induced by administrating 2,4,6 trinitrobenzenesulphonic acid (TNB) rectally in Spragur Dawley female rats. Beginning at the first day of TNB colitis, the rats were treated with zinc sulfate enema once daily for 6 days. The rats were sacrificed at days 8. The effects of zinc sulfate were evaluated by examining mucosal lesion area, mucosal myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, mucosal prostaglandin E 2(PGE 2) and leukotriene B 4(LTB 4) levels. Results TNB induced severe colitis as evidenced by increased mucosal lesion area, mucosal MPO activity and PGE 2 and LTB 4 levels. Six days after the application of the zinc sulfate enema, the mucosal lesion area, MPO activity, PGE 2 and LTB 4 levels were all decreased significantly, except mucosal SOD activity that was remained unchanged after zinc treatments. Conclusions The data suggest that zinc sulfate enemas have an anti inflammatory action on experimental colitis through the mechanism other than increasing SOD activity.

AIM In order to search inhibitors of protein kinase CK2, we observed the inhibitory effects of kaempferol on recombinant human protein kinase CK2 holoenzyme and its kinetics in vitro. METHODSCloning, prokaryotic expression and purification of human protein kinase CK2 α' and β subunits by gene engineering, the two subunits were mixed at equal molar ratio to reconstitute CK2 holoenzyme and identify its biological properties. The CK2 activity was assayed by detecting incorporation of 32P of [γ-32P]ATP into the substrate. The inhibitory effect of kaempferol on CK2 was assayed in the presence of different concentrations of kaempferol. Kinetic analysis of kaempferol-induced inhibition was carried out in the condition that casein concentration was fixed at 2 g·L-1 and ATP was changed at various concentrations(10, 20, 40, 80 μmol·L-1), or ATP was fixed at 10 μmol·L-1 and casein was changed at different concentrations (1, 2, 4, 8 g·L-1). RESULTS Kaempferol was shown to strongly inhibit the holoenzyme activity of recombinant human protein kinase CK2 with IC50 of 1.9 μmol·L-1, which was more effective than chrysin, morin and genistein which are both known as CK2 special inhibitors. Kinetic studies of kaempferol on recombinant human CK2 showed that kaempferol acted as a noncompetitive inhibitor with substrate ATP(Ki=1.1 μmol·L-1) and casein (Ki=3.1 μmol·L-1). CONCLUSIONKaempferol is a novel potent inhibitor of protein kinase CK2 in vitro. Discussions indicate that flavonoid inhibitors of CK2 may adopt different orientations in theactive site of CK2 and that these are determined by the number and position of their hydroxyl groups.

Background:The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is a typical global health concern.The impact of HIV/AIDS is global,and we cannot effectively solve the problem without a global effort.In this study,we report our research on global HIV/AIDS control with an innovative fourdimensional approach.Methods:Countries (n=148) with data available on area size,total population,and the total number of persons living with HIV (PLWH) were included.The HIV epidemic across the globe was described using 4 indicators,including the total count,population-based P rate,geographic area-based G rate,and population and geographic area-based PG rate.Results:A total of 35,426,911 PLWH were included,with a global prevalence rate of 0.51 per 1,000 population.The total PLWH count provided data on resource allocation in individual countries to improve HIV/AIDS care;and the top five countries with the highest PLWH counts were South Africa (7,000),Nigeria (3,500),India (2,100),Kenya (1,500),and Mozambique (1,500).The other three indicators provide a measure to assess the global risk profile of HIV transmission and to provide information on HIV/AIDS prevention strategies.The top five countries with the highest P rates (per 1,000 persons) were Swaziland (170.9),Botswana (154.7),Lesotho (145.2),South Africa (127.4),and Zimbabwe (89.7);the top five countries with the highest G rates (per 100 km2) were Swaziland (1,279.1),Malawi (1,039.5),Lesotho (1,021.1),Rwanda (810.7),and Uganda (748.1);and the top five countries with highest PG rates (per 1,000,000 persons per 100 km2) were Barbados (2,127.9),Swaziland (993.8),Lesotho (478.3),Malta (375.0),and Mauritius (319.7).With PG rate,we detected countries in two hotspots (south and middle Africa and the Caribbean region) and one belt across the Euro-Asian region with high risks of HIV transmission.Conclusions:This study expanded the conventional measures by adding two new indicators,thus forming a new four-dimensional framework to quantify the global HIV epidemic.In addition to gaining a better insight into the epidemic than before,study findings provide new data on country-level and global efforts to end the AIDS epidemic by 2030.

Objective To observe the effect of 7 flavonoids on recombinant human protein kinase CK2 holoenzyme activity and investigate their structure-activity relationship. Methods Recombinant hu-man protein kinase CK2 α' and β subunits were mixed at equal molar ratio to reconstitute CK2 holoen-zyme. The CK2 activity was assayed by detecting incorporation of 32p of [γ-32P] ATP into the substrate for the inhibitory effect by flavonoids and calculation of IC50 was performed according to probability unit (PROBIT) method. Results Myricetin, quercetin, morin, luteolin, kaempferol, apigenin, and chrysin were shown to obviously inhibit recombinant CK2 holoenzyme activity in a concentration-dependent man-ner with IC50 values of 1.18, 0.51, 16.16, 0.86, 1.88, 1.72, and 13.63 umol/L, respectively. Myricetin, quercetin, luteolin, kaempferol, and apigenin were more effective than DRB and A3, which were known as CK2 inhibitors in vitro. Whereas morin and chrysin displayed a similar effect to DRB. Structure-activity study indicated that the major structural requirements for the potent inhibition of CK2 by these flavonoids were hydroxyl group at position 6, 3' and 4'. Different from these requirements, absence of a hydroxyl group at position 3 did not modify their inhibitory potency, while addition of hydroxyl groups at positions 2' or 5' was detrimental to the inhibitory effect on CK2. Conclusion The inhibitory effect of flavonoid on protein kinase CK2 in vitro may be determined by the position of their hydroxyl groups.

Background and purpose:Postoperative recurrence of esophageal cancer is one of the main factors that affect the patients’ prognosis and quality of life. This study mainly investigated the clinical features of thoracic stomach cancer (TSC) after surgical treatment for esophageal carcinoma. Methods:We retrospectively reviewed 51 cases of postoperative TSC in our hospital. Results:10.97% of the cases with TSC were diagnosed by endoscopy. There were 13 cases who also had anastomotic recurrence. The locations of 46 cases (90.2%) in 51 patients were same as the primary cancer. 48 cases of them were squamous cell carcinoma and 3 cases were adenocarcinoma at the time of esophagectomy for esophageal carcinoma. Endoscopic manifestations were puffiness-infiltrating type 39.2%(20/51), massive type 15.7%(8/51), ulcerative type 7.8%(4/51) and ulcer-infiltrating type 33.3%(17/51) and diffuse infiltrating type 3.9(2/51). Conclusion:The incidence of TSC after surgical treatment for esophageal carcinoma was high. The main cause was that the local residual cancer invaded the gastric wall. The gastroscopic features of TSC were different from gastric cancer. The follow up with endoscopy for the postoperative patients with esophageal carcinoma is a primary way to diagnose TSC.

AIM To study the expression, purification and activity assay of recombinant mouse protein kinase CK2? subunit from Escherichia coli. METHEDS The recombinant plasmid containing mouse protein kinase CK2? subunit cDNA constructed successfully was transformed into Escherichia coli BL21 (DE3) and specifically induced by IPTG. The recombinant mouse CK2? subunit was sequentially purified by DE 52, P11 phosphocellulose and Heparin Sepharose chromatography. The purified recombinant protein was analysed by SDS PAGE. RESULTS One protein with molecular mass of 42 ku was overexpressed by inducing ITPG. The recombinant protein was composed of approximately 30 6% of the total bacterial proteins. From 278 mg soluble proteins, the yield of the CK2? protein was 4 7 mg. SDS PAGE analysis of the purified recombinant protein showed only one band in agreement with native mouse CK2? subunit. The recombinant mouse CK2? and ? subunits were mixed at the same molar ratio. The produced CK2 holoenzyme displayed full activity. The characteristics and functions of reconstituted CK2 holoenzyme were consistent with those of the given native CK2. CONCLUSION The recombinant protein is mouse protein kinase CK2? subunit.

Objective To observe the changes of plasma ghrelin in patients with severe sepsis and to explore the correlation of the plasma ghrelin and cytokines with sepsis.Methods Choose the healthy volunteer(n=10)as control group,and measure the plasma ghrelin(by ELISA),TNF-?,IL-1?,PCT(procalcitonin)and CRP at the 1st day,3rd day and 10th day in sepsis group(n=26).Results The plasma ghrelin level in sepsis group increased significantly compared with control group(P

Objective: To study the clinical features of primary biliary cirrhosis (PBC) in order to facilitate cognition of the disease. Methods: Clinical data of 42 patients clinically and/or histologically diagnosed with PBC were reviewed. Anti mitochondrial antibody (AMA) negative/positive patients as well as the patients who were/were not associated with Sj?gren Syndrome (SS) were compared in terms of clinical, biochemical and immunological features. Results: Among the 42 patients, 78.6%(33/42) of the cases were females; the mean age at diagnosis was (61.1?10.8) years. The most frequent symptoms were fatigue. Serum alkaline phosphatase (ALP), ?-glutamyltranspeptidase (?-GT) and total bile acid (TBA) levels were markedly elevated in the majority of the patients, whereas ALT and AST levels were mildly to moderately elevated. Thirty-one patients had a total bilirubin (TBil) level above normal. The levels of TBil and prothrombin time had positive correlationship with years of the course (P=0.000, r=0.696; P=0.005, r=0.424), whereas serum albumin level had negative correlationship with years of the course (P=0.002, r=-0.462). Thirty-seven patients had elevated serum IgM and 34 patients were AMA/AMA-M2 positive. AMA negative and AMA positive patients were similar in terms of clinical manifestations and liver biochemistries findings. Serum IgM and IgA levels were significantly lower, whereas total cholesterol level was higher in AMA negative patients when compared with AMA positive cases. Fifteen cases were associated with SS, which were similar in terms of clinical, biochemical and immunological features when compared with the PBC patients were not associated with SS. Conclusion: PBC is mostly found in middle aged and old women. Elevated serum ALP, TBA and ?-GT levels together with positive AMA/AMA-M2 can help to diagnose PBC. AMA negative PBC patients are characterized by relatively lower serum IgM and IgA levels and higher total cholesterol level. PBC patients who are associated with SS have not substantial differences in the clinical, biochemical and immunological spectra of the disease.

Objective To assess the effects of different administration timing of prophylactic antibiotics on infections after hip arthroplasty. Methods 535 patients having undergone arthroplasty were divided into two groups: the experiment group (n=273)and the control group (n=262): The former groupwere administered with antibiotics until 24 hours postoperatively and the latter until 72 hours postoperatively. The two groups were compared in terms of postoperative infection rate. Results The infection rates in the experimental groupand the control group were 4.396%and 3..817%, with insignificant differencebetween them. Conclusion For those patients undergoing hip arthroplasty, extended administration of antibiotics after operation (over 48 hours) may not reduce the risk of recent the infection rate.