Objective To observe the therapeutic effect and mechanism of allicin on uremic-induced myocardial injury in rats.Methods Twenty-four rats were randomly divided into sham-operated group,model group,and low-,and high-dose allicin groups,with six rats in each group.Except for the sham-operated group,the uremic-induced myocardial injury model was constructed using the 5/6 nephrectomy method in all other groups of rats.After successful modeling,corresponding interventions were carried outed.At the end of the intervention,the renal function of rats was observed,the cardiac mass index was calculated,the levels of serum high-sensitive cardiac troponinⅠ(hs-cTnI)and creatine kinase isoenzyme(CK-MB)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological changes of rat cardiac tissues were observed by hematoxylin-eosin(HE)staining,the changes of autophagosomes and autolysosomes were observed by transmission electron microscopy,and the protein expressions of PTEN-induced putative kinase 1(PINK1)and E3 ubiquitin protein ligase(Parkin)in myocardial tissues were detected by Western Blot.Results Compared with the sham-operated group,the serum creatinine(SCr),blood urine nitrogen(BUN),cardiac mass index,CK-MB and hs-cTnI in rats in the model group were elevated(P<0.05),the pathological damage of cardiac tissues were obvious,and the autophagosomes and autolysosomes were decreased,and PINK1 and Parkin protein expressions in myocardial tissues were decreased(P<0.05);compared with the model group,SCr,BUN,cardiac mass index,CK-MB and hs-cTnI in allicin low-and hogh-dose groups were decreased,the changes of pathological damage of cardiac tissues were relieved,the autophagosomes and autolysosomes were increased,and PINK1 and Parkin protein expressions in myocardial tissues were increased(P<0.05).Conclusion Allicin can reduce myocardial injury in uremic rats,and its mechanism may be related to the up-regulation of PINK1/Parkin-mediated mitochondrial autophagy.

Myocardial injury is the leading cause of death in uremic patients.PINK 1/Parkin-mediated mitochondrial autophagy is involved in the progression of myocardial injury.In recent years,pathogenic turbidity has been gradually accepted as a representative of a new type of toxic pathogens by the researchers of traditional Chinese medicine(TCM).This paper sorts out literature about pathogenic turbidity,analyzes the etiological and pathogenic characteristics of pathogenic turbidity,and suggests that the pathogenesis of uremia-induced myocardial injury can be more comprehensively clarified from the perspective of healthy-qi deficiency resulting in latent pathogenic turbidity.In the patients with uremia,the down-regulation of PINK1/Parkin causes the weakening of mitochondrial autophagy,which leads to the elevation of levels of reactive oxygen species(ROS)and inflammatory factors,and eventually causes the injury of myocardial cell.The above pathogenic mechanism is similar to the process of traditional Chinese medicine(TCM)in which the deficiency of the healthy-qi(in particular kidney deficiency)results in the production of the pathogenic turbidity(showing as dampness,blood stasis,phlegm,toxin and so on)and then causes the pathogenic turbidity hide in vessels and collaterals and gradually injure the heart vessels,and eventually results in the deficiency of heart vessels.The mitochondrial autophagy mechanism mediated by the PINK1/Parkin pathway is suitalbe for explaining the TCM pathogenesis of uremia-induced myocardial injury,characterized by healthy-qi deficiency resulting in latent pathogenic turbidity,and also is suitable for interpretating the principle of supporting healthy-qi to eliminate pathogenic turbidity for treating uremia-induced myocardial injury.Under the guidance of the theory of health y-qi deficiency and turbid pathogens in TCM,the development of specific PINK 1/Parkin agonists may expand the approach for the treatment of uremia-induced myocardial injury.

Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.

The poly ADP-ribose polymerase (PARP) is a class of nuclear enzymes highly expressed in eukaryotic cells and plays a key role in DNA damage repair. In recent years, PARP inhibitors have shown great potential in tumor therapy, and several PARP inhibitors have been approved by the FDA for maintenance therapy of a variety of cancers. PARP inhibitors mainly inhibit PARP enzymes and PARP trapping, resulting in the persistence of DNA single strand breaks, which are converted to double strand breaks during DNA replication. Studies have shown that PARP inhibitors not only have a significant anti-tumor effect, but also have a synergistic effect with radiotherapy. This paper reviewed the potential theoretical basis of PARP inhibitor combined with radiotherapy, summarized the recent progress of preclinical and clinical research on PARP inhibitors in tumor radiotherapy, sorted out the urgent problems in this field, and looked into the application prospect of PARP inhibitors in anti-tumor therapy.

Objective To study the effects of diacerein and its metabolite rhein on plasma inflammatory cytokine level and expression of perirenal adipose tissue chemerin in type 2 diabetes mellitus (T2DM) rats and its role in regulating glucose and lipid metabolism.Methods We randomly divided 56 SD male rats into 5 groups: normal control group (Group A), T2DM group (Group B), pioglitazone group (Group C), diacerein group (Group D), and pioglitazone+diacerein group (Group E).Group A was fed with ordinary feed whereas the other groups were fed with high-fat diet.At the end of week 8, rats in Groups B, C, D and E were injected intraperitoneally with 30mg/kg of STZ solution to create the model.Those in Group A were injected with the same volume of sterile sodium citrate solution.OGTT examination was taken to screen the model rats at the end of week 10.The successful mode was chosen according to OGTT result.Then Group C was treated with pioglitazone 10mg/(kg·d) orally, Group D with diacerein 50mg/(kg·d), Group E with pioglitazone 10mg/(kg·d)+diacerein 50mg/(kg·d), and Group A and B were given the same volume of normal saline.The intervention lasted 4 weeks.At the end of experiment weeks 10 and 14, FBG, FINS, TC, TG, LDL-C, IL-1β, IL-6, and TNF-α were detected in the fasting rats with free access to water.After blood sample was taken at the end of week 14, all rats were killed and theperirenal adipose tissue was isolated, the expression of chemerin in perirenal adipose tissue was detected by Western blotting.Results At the end of week 10, FBG, FINS, TG, TC, LDL-C, IL-1β, IL-6, and TNF-α were higher in Groups B, C, D and E than in Group A while HDL-C was lower (all P<0.01).At the end of week 14, TC, TG, and LDL-C were lower in Groups C, D and E than in Group B but higher than Group A while HDL-C was lower than in Group A (all P<0.05).Group E had greater changes in glucose and lipid metabolism and inflammatory cytokine level than Groups C and D (P<0.05).Western blotting results showed that the expression of chemerin in perirenal adipose tissue increased higher in Group B than in Groups A, C, D and E (P<0.05).The expression of chemerin were also higher in Groups C and D than in Groups A and E (P<0.05), but there was no significant difference between Groups A and E.Conclusion Diacerein can regulate the metabolism of glucose and lipid, improve insulin resistance by reducing the expression of chemerin and the level of inflammatory cytokines.

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.

Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P<0.05) , and the levels of TC , TG, FINS, LDL-C, ALT, AST, IL-1βin the other 3 groups increased significantly compared with normal control group (P<0.05).At the end of 10th week, in comparison with normal control group , the levels of FBG , FINS, TC, TG, LDL-C, ALT, AST and IL-1βincreased significantly ( P<0.05) , while the levels of HDL-C and ISI decreased significantly (P<0.01).Moreover, the levels of FINS, TC, TG, LDL-C, ALT, AST and IL-1βat 10th weekend increased significantly compared with those at 8th weekend(P<0.05).At the end of 14th week, the FBG levels in T2DM group, pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.01), while compared with T2DM group, the FBG level in pioglitazone intervention group decreased and the levels of HbA 1c, TC, TG, LDL-C and ALT in pioglitazone intervention group and diacerein treatment group decreased ( P<0.05) along with the increased ISI and HDL-C levels ( P<0.05) .Compared with the results at 10th weekend , the levels of FBG , HbA1c, LDL-C, ALT, AST in T2DM group in-creased (P<0.05) while the levels of HbA1c, TC, ALT, AST and IL-1βin pioglitazone intervention group and diacerein treatment group decreased significantly at 14th weekend(P<0.01).The expression level of PPAR-γin pioglitazone intervention group (0.91± 0.03) was significantly higher than normal control group (0.82±0.15), T2DM group(0.75±0.28) and diacerein treatment group (0.83± 0.34) ( P<0.01) , and no significant difference was found between diacerein treatment group and normal control group( P>0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.

OBJECTIVETo investigate the epidemic status of Hepatitis B in children aged 1-14 in 3 counties of Guangdong province in 2013, and to evaluate the effect of hepatitis control in children aged 1-14 after hepatitis B vaccine was integrated into the national immunization program in 2002 and catch-up vaccination was conducted from 2009 to 2011.

METHODSA multi-stage stratified random sampling was designed to survey 1 621 children aged 1-14 in rural area of Nanxiong county, Haifeng county and Xinxing county by questionnaires including general information, medical history and risk factors. The samples were tested with chemiluminescence method to detect hepatitis B virus (HBV) surface antigen (HBsAg), antibody to HbsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc). Chi-square test was used to compare the positive rate of HBV serum markers in different age groups, vaccine histories, birth weight and HBV infection status of mother.

RESULTSAmong the children aged 1-14 in 3 counties rural regions of Guangdong province, the positive rate of HBsAg, anti-HBs, and anti-HBc was 1.11% (18/1 621), 60.69% (982/1 618) and 1.92% (31/1 617), respectively. The HBsAg positive rate of vaccinated children (0.84%, 13/1 547) was lower than that of unvaccinated children (1/13) or children with unknown vaccination status (6.56%, 4/61) (χ² = 22.64, P < 0.001). The HBsAg positive rate (0.45%, 5/1 118) of the children with birth-dose given within 24 hours was lower than those that of children given beyond 24 hours (2.63%, 61/190) (χ² = 10.21, P < 0.001). The HBsAg positive rate (5/18) of children with birth weight under 2 kilogram was higher than that of children with birth weight above 2 kilogram (0.78%, 12/1 548) (χ² = 120.8, P < 0.001). The HBsAg positive rate of children born to HBsAg-positive mothers (2.80%, 3/107) was higher than that of children born to HBsAg-negative mothers (0.21%, 1/470) (χ² = 8.50, P = 0.004). With the age increasing, the coverage and timely birth-dose coverage of Hepatitis B vaccine (HepB) decreased, and the positive rate of anti-HBs gradually decreased.

CONCLUSIONAfter the catch-up vaccination was conducted in unvaccinated children aged 1-14 years from 2009 to 2011, the HBsAg and anti-HBc positive rate decreased, while the anti-HBs positive rate increased significantly.

Adolescent ; Birth Weight ; Child ; Child, Preschool ; China ; epidemiology ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; Humans ; Immunization Programs ; Infant ; Risk Factors ; Rural Population ; Seroepidemiologic Studies ; Surveys and Questionnaires

Objective To investigate the epidemic status of Hepatitis B in children aged 1-14 in 3 counties of Guangdong province in 2013,and to evaluate the effect of hepatitis control in children aged 1-14 after hepatitis B vaccine was integrated into the national immunization program in 2002 and catch-up vaccination was conducted from 2009 to 2011. Methods A multi-stage stratified random sampling was designed to survey 1 621 children aged 1-14 in rural area of Nanxiong county, Haifeng county and Xinxing county by questionnaires including general information, medical history and risk factors .The samples were tested with chemiluminescence method to detect hepatitis B virus (HBV) surface antigen ( HBsAg), antibody to HbsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc).Chi-square test was used to compare the positive rate of HBV serum markers in different age groups, vaccine histories, birth weight and HBV infection status of mother. Results Among the children aged 1-14 in 3 counties rural regions of Guangdong province, the positive rate of HBsAg,anti-HBs,and anti-HBc was 1.11% (18/1 621), 60.69%(982/1 618) and 1.92% (31/1 617), respectively. The HBsAg positive rate of vaccinated children (0.84%, 13/1 547) was lower than that of unvaccinated children (1/13) or children with unknown vaccination status (6.56%,4/61) (χ2=22.64,P<0.001). The HBsAg positive rate (0.45%,5/1 118) of the children with
birth-dose given within 24 hours was lower than those that of children given beyond 24 hours (2.63%, 61/190) (χ2=10.21 ,P<0.001). The HBsAg positive rate(5/18) of children with birth weight under 2 kilogram was higher than that of children with birth weight above 2 kilogram(0.78%,12/1 548)(χ2=120.8,P<0.001).The HBsAg positive rate of children born to HBsAg-positive mothers (2.80%,3/107) was higher than that of children born to HBsAg-negative mothers (0.21%,1/470)(χ2=8.50,P=0.004). With the age increasing, the coverage and timely birth-dose coverage of Hepatitis B vaccine(HepB) decreased,and the positive rate of anti-HBs gradually decreased . Conclusion After the catch-up vaccination was conducted in unvaccinated children aged 1-14 years from 2009 to 2011, the HBsAg and anti-HBc positive rate decreased, while the anti-HBs positive rate increased significantly.

Objective To investigate the epidemic status of Hepatitis B in children aged 1-14 in 3 counties of Guangdong province in 2013,and to evaluate the effect of hepatitis control in children aged 1-14 after hepatitis B vaccine was integrated into the national immunization program in 2002 and catch-up vaccination was conducted from 2009 to 2011. Methods A multi-stage stratified random sampling was designed to survey 1 621 children aged 1-14 in rural area of Nanxiong county, Haifeng county and Xinxing county by questionnaires including general information, medical history and risk factors .The samples were tested with chemiluminescence method to detect hepatitis B virus (HBV) surface antigen ( HBsAg), antibody to HbsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc).Chi-square test was used to compare the positive rate of HBV serum markers in different age groups, vaccine histories, birth weight and HBV infection status of mother. Results Among the children aged 1-14 in 3 counties rural regions of Guangdong province, the positive rate of HBsAg,anti-HBs,and anti-HBc was 1.11% (18/1 621), 60.69%(982/1 618) and 1.92% (31/1 617), respectively. The HBsAg positive rate of vaccinated children (0.84%, 13/1 547) was lower than that of unvaccinated children (1/13) or children with unknown vaccination status (6.56%,4/61) (χ2=22.64,P<0.001). The HBsAg positive rate (0.45%,5/1 118) of the children with
birth-dose given within 24 hours was lower than those that of children given beyond 24 hours (2.63%, 61/190) (χ2=10.21 ,P<0.001). The HBsAg positive rate(5/18) of children with birth weight under 2 kilogram was higher than that of children with birth weight above 2 kilogram(0.78%,12/1 548)(χ2=120.8,P<0.001).The HBsAg positive rate of children born to HBsAg-positive mothers (2.80%,3/107) was higher than that of children born to HBsAg-negative mothers (0.21%,1/470)(χ2=8.50,P=0.004). With the age increasing, the coverage and timely birth-dose coverage of Hepatitis B vaccine(HepB) decreased,and the positive rate of anti-HBs gradually decreased . Conclusion After the catch-up vaccination was conducted in unvaccinated children aged 1-14 years from 2009 to 2011, the HBsAg and anti-HBc positive rate decreased, while the anti-HBs positive rate increased significantly.