OBJECTIVE:To provide reference for promoting the development of related legislation work on ensuring pediatric drug use in China. METHODS:The legislation process of pediatric drug use in US,the effects of current Best Pharmaceuticals for Children Act and Pediatric Research Equity Act on pediatric drug use in US were intrduced and analyzed,suggestions on guarantee-ing the accessibility and safety on pediatric drug use in China were put forward. RESULTS & CONCLUSIONS:The policy6-month period of pediatric exclusive protectionin Best Pharmaceuticals for Children Act has motivated the enthusiasm of phar-maceutical companies developing pediatric studies,while it affects the marketing of generic drugs. Pediatric Research Equity Act has achieved remarkable effect in terms of ensuring the safety of pediatric drug use by forcing pharmaceutical companies to carry out pediatrics assessments,while there is no enough force for the marketed drugs that has not been widely used for children. En-couragement and enforcement are useful methods for promoting development of pediatric drug use. It is suggested to take measures like modifingone drug two formsin Prescription Management Regulations,accelerating approvals of related pediatric drugs on the premise that safety is guaranteed,implementing tax preference for related pharmaceutical companies that produced pediatric drugs,promoting the entry of drug reimbursement list and empowering CFDA to force pharmaceutical companies to implement pedi-atric studies to promote the accessibility and safety of pediatric drugs.

Aim To investigate the effect of asiatic acid on apoptosis and autophagy in human glioblastoma T98G cells. Methods MTT colorimetry was employed to assay the cellular proliferating activity. The fluores-cence microscope and Hoechst 33258 staining were used to detect the morphological changes. The cell ap-optosis and autophagy were analyzed by flow cytometry with Annexin-V/7-AAD and MDC staining respective-ly. The expressions of associated proteins were detected by Western blot to analyze the mechanism of apoptosis and autophagy. Results MTT assay showed that the growth of T 9 8 G cells was inhibited by asiatic acid ( IC50 =46. 3 μmol · L-1 ) . Annexin V/7-AAD stai-ning and Western blot revealed that asiatic acid in-duced apoptosis in T98 G cells by reducing the expres-sion of Akt, decreasing the mitochondrial membrane potential, and increasing the expression of Caspase-3. MDC staining and Western blot showed that the per-centage of MDC-positive cells was decreased and the expressions of Beclin-1 , LC3-II and Atgs were inhibi-ted by asiatic acid treatment. 5 μmol·L-1 chloroquine was used to up-regulate the expressions of LC3-Ⅱand Beclin-1 . Asiatic acid-inhibited autophagy was blocked and the total apoptotic rate was reduced remarkably. Conclusion Asiatic acid suppresses T98 G cells pro-liferation by inducing apoptosis and inhibiting cell au-tophagy, and the very role of inhibiting autophagy could promote apoptosis to a certain extent.

Objective To study the influence of carboxymethyl-chitosan(CM-chitosan)on chondro- cyte apoptosis induced by recombinant human interleukin-1?(rhIL-1?)and explore its mechanism.Methods Rabbit chondrocytes were isolated and cultured.Chondrocytes were pretreated with different concentrations of CM-chitosan for 1 h,then 10 ng/ml IL-1?were added into the culture medium.After 24 h,the apoptotic rates of chondrocytes were measured by flow cytometry with AnnexinⅤ-FITC and PI staining.The morphology of nuclei was observed by fluorescent microscopy with Hoechst 33342 staining.The mitochondrial membrane po- tentials were tested by confocal laser scanning microsocopy with Rhodamine-123 and ATP contents were mea- sured by luciferase reaction.Results CM-chitosan could inhibit chondrocyte apoptosis and restore the func- tion of mitochondria induced by IL-113 in a dose-dependent manner.Conclusion CM-ehitosan can inhibit chondrocyte apoptosis by protecting mitochondrial function.

Objective:To discuss the type, treatment and results of different therapies of biliary fistula after orthotopic liver tansplantation(OLT).Methods:Data of 24 patients who developed biliary fistula after OLT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to March 2019 were retrospectively analyzed. Patients with biliary fistula were classified into 4 types according to presence or absence of stricture. All patients were treated by endoscopic retrograde cholangiopancreatography (ERCP) or interventional therapy, including endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary drainage (ERBD) or percuteneous transhepatic cholangial drainage (PTCD). Main outcome measurements were the onset time of biliary fistula, the site of biliary fistula, the complications of ERCP or PTCD, the time of removing abdominal or biliary drainage tube, and the onset of new biliary stricture.Results:Biliary fistula was found in (46.5±36.6) days (6-122 days) after OLT. The numbers of patients in four types of biliary fistula were 6, 14, 2 and 2, respectively. Biliary fistula was cured in 22 patients, with clinical cure rate of 91.7%. All patients underwent ERCP first, and the technical success rate and clinical cure rate were 87.5% (21/24) and 85.7% (18/21), respectively. The clinical cure rates of ERCP forⅠ-Ⅳ biliary fistula were 6/6, 84.6%(11/13), 1/2, and 0, respectively. The clinical cure rates of ENBD and ERBD were 8/10 and 6/8, respectively. Five cases in whom ERCP failed, underwent PTCD, with technical success and clinical cure rates of 4/5 and 3/4 respectively. Eight patients(33.3%)developed cholangitis after treatment, and the incidence rate seemed higher in type Ⅱ biliary fistula than that in type Ⅰ [35.7% (5/14) VS 16.7% (1/6)]. Incidence of cholangitis was higher in patients with non-anastomotic stricture than those with anastomotic stricture [83.3%(5/6) VS 16.7%(3/18)].Conclusion:The first line treatment for biliary fistula after OLT is ERCP, followed by PTCD. The best procedures of biliary fistula typeⅠ-Ⅳ were ENBD, ENBD combined with ERBD, ENBD and PTCD, respectively.

Objective To analyze the expression of IFIT4,PRKR and investigate the clinical and immunology features of different types of liver involvement in patients with systemic lupus erythematosus (SLE).Methods Clinical data of 62 cases of SLE with liver damage and 62 cases of SLE without liver damage were collected.Peripheral venous blood samples were obtained and total RNA were extracted and transcribed into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression levels of IFIT4,PRKR in patients with SLE.Clinical parameters were analyzed by ANOVA,Chi-square test,Pearson's or Spearman's test.Results ① The increase of γ-GT or ALP was correlated with rash and oral ulcer (x2=5.625,P=0.018),lupus nephritis (x2=5.631,P=0.019),anemia,thrombocytopenia (99±21,P=0.028; 81±45,P=0.004,),CRP (33±43,P=0.004).The positive rate of nRNP (x2=4.862,P=0.027 ) and SSA (x2=8.087,P=0.004) was higher in patients with liver damage than other groups; ② The positive rate of anti-Rib antibody in SLE with liver damage was significantly higher than SLE without liver damage (x2=19.542,P=0.000); ③ There was no difference in the expression of IFIT4 among these groups,but higher expression of PRKR was detected in the group of patients with increased γ-glutamyl transpeptidase (γ-GT) or ALP(F=3.54,P=0.018).Conclusion The different types of liver damage in SLE patients have different clinical and immunology characteristics.The expression of PRKR is higher in patients with increased γ-GT or ALP.

Aged ; Branchioma ; pathology ; Carcinoma, Squamous Cell ; pathology ; Head and Neck Neoplasms ; pathology ; Humans ; Male

Objective Overexpressions of epidermal growth factor(EGF)and EGF receptor have been associ- ated with progression and invasive phenotype of pancreatic cancer.However,the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood.In this study,effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated.Methods The effects of EGF on the proliferation,adhesion and invasion of pancreatic cancer cells were detected by WST-1 prolif- eration assay,adhesion assay and invasive assay,respectively.The activity and expression of MMP-2 and MMP-9 were examined by zymography,Western blot and RT-PCR,respectively.The activity of NF-?B was examined by EMSA.Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion.The expressions of NF-?B and MMP-9 were significantly increased by EGF,but EGF did not affect the activity and expression of MMP-2.Furthermore,EGF stimulated the NF-?B binding activity.Pre- treatment with NF-?B inhibitors,pyrrolidine dithiocarbamate(PDTC),could significantly inhibit the activity of NF-?B induced by EGF.Meanwhile,the EGF-induced expression and activity of MMP-9,as well as cell invasiveness were also inhibited by NF-?B inhibitor.Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF-?B in pancreatic cancer cells,which implies that NF-?B inhibitant,such as PDTC,may diminish the invasiveness of pancreatic cancer cells.

Objective: To understand the epidemiological characteristics of nonfatal injury and its influencing factors among middle school students in Zhejiang Province,and to provide evidence for prevention and control of nonfatal injury of adolescents. Methods: Using multi-stage stratified cluster sampling method,24 157 middle school students from 442 schools in 30 counties（cities,districts）of Zhejiang Province were selected to investigate socio-demographic characteristics,the occurrence of nonfatal injury and injury-related behaviors from April to May of 2017. Logistic regression model was used to analyze influencing factors for nonfatal injury among middle school students. Results: The incidence of nonfatal injuries in 23 462 secondary school students in the past 12 months was 20.86%. The incidence of nonfatal injury was 24.15% in boys,which was higher than 17.33% in girls（P<0.05）. The incidence of nonfatal injury was 20.17% in urban students and 21.19% in rural students,and the difference between them was not statistically significant（P>0.05）. The incidence of nonfatal injury was 22.17% in junior high school students,19.42% in senior high school students and 19.51% in vocational high school students,and there was statistically significant difference between them（P<0.05）. The results of the multivariate logistic regression analysis showed that boys（girls：OR=0.805,95%CI：0.728-0.890）,poor academic performance（OR=1.149,95%CI：1.018-1.298）,smoking（OR=1.260,95%CI：1.083-1.466）,drinking（OR=1.410,95%CI：1.279-1.553）,more physical activity（OR：1.244- 1.527,95%CI：1.098-1.767）,loneliness（OR：1.336-1.500,95%CI：1.219-1.682）,sadness（OR=1.308,95%CI：1.186-1.441）,absenteeism（OR=1.390,95%CI：1.182-1.634）,running away from home（OR=1.242,95%CI：1.076- 1.435）,fighting（OR=1.771,95%CI：1.594-1.967）and being bullied（OR=2.071,95%CI：1.869-2.294）were risk factors for nonfatal injury in middle school students. Conclusion The incidence of nonfatal injuries among secondary school students was 20.86%. Male students were the high risk group. The incidence of nonfatal injury was related to gender,smoking,drinking,negative emotions and violence.

Objective:To investigate roles of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice.Methods:A total of 152 male Balb/c mice (8-week old) were randomly divided into a sham group,a septic model group,an allicin treatment group,and an autophagy inhibition group.Septic mouse model was established by cecal ligation and puncture (CLP).Mice in the allicin treatment group were given allicin (30 mg/kg,intra-peritoneal injection) at 6 and 12 h,while those in the autophagy inhibition group were given autophagy inhibitor 3-MA (15 mg/kg,intra-peritoneal injection) at half an hour after allicin administration.Mice in the model and sham group were administered with the same amount of saline.Twenty mice in each group were randomly chosen to observe the 7 d survival rate.The other 12 mice were killed at 24 h,and the bronchoalveolar lavage fluid (BALF) (n=6) and lung tissues (n=6) were collected.ELISA was used to detect the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF.Hematoxylin-eosin staining was preformed to show the morphological changes in the lung tissues.Malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) in the lung tissues were examined.The expression of LC3B and Beclin-1 was determined by immunohistochemical analysis.Results:Compared with the sham group,the 7 d survival rate and lung SOD activity were decreased in the CLP group (P<0.05);the lung morphological damage score,the levels of TNF-α and IL-6 in the BALF,MDA content in the lung,and expression of LC3B and Beclin-1 were increased greatly in the CLP group (P<0.05).Compared with the CLP group,the 7 d survival rate,lung SOD activity and the expressions of LC3B and Beclin-1 were increased significantly in the allicin treatment group (P<0.05);the lung morphological damage scores,the levels of TNF-α and IL-6 in the BALF and MDA content in the lung were decreased obviously in the allicin treatment group (P<0.05).Compared with the allicin treatment group,the 7 d survival rate,lung SOD activity,and the expressions of LC3B and Beclin-1 were decreased in the 3-MA group (P<0.05);the lung morphological damage scores,the levels of TNF-α and IL-6 in the BALF,and MDA content in the lung were increased significantly in the 3-MA group (P<0.05).Conclusion:Allicin may ameliorate sepsis-induced acute lung injury in mice by enhancing the level of autophagy.

Objective To understand the pattern of and influencing factors on leisure time physical exercises among adults in Zhejiang. Method Totally 17 437 residents aged 18 years and over selected by stratified cluster random sampling in Zhejiang in 2010 were investigated. Result Overall 21.82%(95%CI:17.12%-27.38%) of adults took part in leisure time physical exercises in 2010. The proportion was higher in urban (29.04%,95%CI:23.46%-35.33%) than in rural (18.81%,95%CI:12.89%-26.61%) (χ2=222.06, P<0.05) areas, and also higher in females (22.91%,95%CI:17.66%-29.15%) than in males (20.56%,95%CI:16.39%-25.48%) (χ2=13.94, P<0.05). Adults aged 18-24 and 55-74 years were more likely to take apart in physical exercises (χ2=266.73, P<0.05), and the lowest proportion was found among farmers (5.33%,95%CI:3.99%-7.11%) (χ2=2 078.40, P<0.05). These proportions both increased along with education level and family income increase (χ2=444.87, P<0.05;χ2=332.20, P<0.05). Overall 83.04%and 90.08%of physical exercisers took part in exercises at least 3 times per week and 30 minutes per time, only 30.67% of those reached moderate or vigorous intensity, and overall 5.38% (95%CI: 3.85%-7.48%) of adults took part in regular leisure time physical exercises in 2010. Multiple logistic regression showed that age, education level, occupation and chronic disease history have influence on regular physical exercises. Conclusion The leisure time physical exercises level was generally low among adults in Zhejiang. Young and middle-aged adults with less education and low income especially farmers should be put on emphasis.