Formulating a well-defined research question and developing a scientifically sound study protocol is important for ensuring the quality of pharmacoepidemiological research.Based on the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition),this research provided an interpretation of the sections related to the formulation of research questions and the development of study protocols.First,it clarified the sources and scope of research questions,outlining a two-step approach—question generation and definition—and introduces relevant evaluation tools and defining frameworks.Furthermore,it systematically explained the key elements of a study protocol and provides an in-depth explanation of the research methodology and its critical aspects.Finally,the paper highlighted the importance of feasibility assessment,emphasizing that the process of defining research questions and study protocols is dynamic and iterative.Compared with the previous edition,the 2nd edition of the guidelines offers more detailed and updated guidance on question formulation and protocol development.It added three new elements—such as protocol archiving or registration—and three new content items,including study objectives.The 2nd edition also expanded the methodological framework and strengthens feasibility assessments,thereby enhancing the comprehensiveness and rigor of its practical guidance.By integrating guideline content with practical experience,this paper provided insights into its implications for pharmacoepidemiological research and serves as a reference for researchers in the field.

Formulating a well-defined research question and developing a scientifically sound study protocol is important for ensuring the quality of pharmacoepidemiological research.Based on the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition),this research provided an interpretation of the sections related to the formulation of research questions and the development of study protocols.First,it clarified the sources and scope of research questions,outlining a two-step approach—question generation and definition—and introduces relevant evaluation tools and defining frameworks.Furthermore,it systematically explained the key elements of a study protocol and provides an in-depth explanation of the research methodology and its critical aspects.Finally,the paper highlighted the importance of feasibility assessment,emphasizing that the process of defining research questions and study protocols is dynamic and iterative.Compared with the previous edition,the 2nd edition of the guidelines offers more detailed and updated guidance on question formulation and protocol development.It added three new elements—such as protocol archiving or registration—and three new content items,including study objectives.The 2nd edition also expanded the methodological framework and strengthens feasibility assessments,thereby enhancing the comprehensiveness and rigor of its practical guidance.By integrating guideline content with practical experience,this paper provided insights into its implications for pharmacoepidemiological research and serves as a reference for researchers in the field.

Objective To study the risk factors related to the severity of post-ERCP hemorrhage in the patients with choledocholithiasis.Methods Clinical data of 56 patients with choledocholithiasis and post -ERCP hemorrhage from January 2008 to August 2015 were analyzed.Made the occurrence of severe hemorrhage as dependent variable,supposed 18 factors in patients and procedure related aspects as possible covariates,analyzed with univariate and binary logistic regression.Results Severe hemorrhage was occurred in 1 1 patients after ERCP.Among patients related factors,female,history of oral corticosteriod,level of bilirubin,size of stone,periampullary diverticula, prolonged time of bleeding-cruor,acute cholangitis,acute pancreatitis and course of disease were proved to be signifi-cant risk factors by univariate analysis(P<0.01 ).Periampullary diverticula,prolonged time of bleeding-cruor and acute cholangitis were independent risk factors in further multivariate analysis(P=0.023,0.036,0.045).Among procedure related factors,EPBD(P<0.01),EST(P<0.01),residual biliary stones(P=0.029)were proved to be significant risk factors by univariate analysis,and EPBD was found as independent risk factor(P=0.029)by multiva-riate analysis.Conclusion Appearance of periampullary diverticula,prolonged time of bleeding -cruor and acute cholangitis were considered as risk factors related to severity of post-ERCP hemorrhage in patients with choledocholi-thiasis.Moreover,EPBD was also an independent risk factor which might aggravate severity of post-ERCP hemor-rhage.

Objective To study the significance of S100A12 in patients with acute pancreatitis (AP).Methods 139 patients with AP were divided into the severe acute pancreatitis (SAP) and moderate acute pancreatitis (MAP) groups.61 patients in the SAP group were further subdivided into the infection group (n =32) and the non-infection group (n =29) based on the presence/absence of secondary infection.Serum samples of these patients were collected on the 3rd,7th and 14th day after treatment.ELISA was used to determinate the S100A12,IL-1 β and IL-6 levels in serum.The area under ROC was used to evaluate the predictive role of S100A12,IL-1β,IL-6 and CRP for infection in patients with SAP.Results The S100A12,IL-1β and IL-6 levels in SAP patients were markedly higher than those in MAP patients and normal controls on the 3rd,7th and 14th day after treatment.These levels decreased toward normal range in MAP patients.They were persistently high in SAP patients after treatment for 7 days,but decreased significantly after 14 days.The serum levels of S100A12,IL-1β,IL-6 and CRP were significantly higher in the infection subgroup(647.5 ± 300.1,155.9 ±48.5,95.7 ±25.5,166.8 ±53.0) than the non-infection subgroup(249.0 ± 176.3,108.0 ± 46.1,64.0 ±38.5,117.9 ±34.9) (P ＜0.05).The sensitivity and specificity of serum S100A12 in diagnosing secondary infection in SAP were 96.8％ and 83.3％,which were higher than those of serum IL-1β,IL-6 or CRP.Conclusion The level of S100A12 was associated with systemic inflammatory response syndrome (SIRS) in AP,and it may serve as a new marker in early diagnosis of SAP and in secondary infection in SAP.

Objective To evaluate the correlation between human serum S100A12 level and severity of acute pancreatitis (AP).Methods Serum S100A12 were tested in 64 AP patients in 24 hours after the onset.S 100A12 levels was compared to the severity of AP,and the area under the curve (AUC) of the receiver operating characteristic curve(ROC) of serum S100A12 levels for estimating the severity of AP were made and compared with laboratory parameters and APACHE-Ⅱ,Ranson' s scoring system.Results S100A12 levels in early AP patients were higher than healthy controls (P ＜ 0.05).S100A12 levels increased and correlated with MCTSI scores:patients scored 7-8 ＞ patients scored 4-6 ＞patients scored less than 4 (P ＜ 0.01).S100A 12 levels increased with organ failure (P ＜ 0.01).The AUC of S100A12 in 24 hours after onset for distinguishing MAP between MSAP and SAP was 0.80,cut-off point was 61.83 ng/ml,sensitivity was 70.01％ and the specificity was 73.52％.Serum S100A12 levels were higher in SAP than in MSAP(P =0.01).The AUC of S100A12 in early AP for distinguishing between MSAP and SAP was 0.84,cut-off point was 285.32 ng/ml,the sensitivity was 76.94％ and the specificity was 94.12％,Youden index was 71.00％,positive likelihood ratio was 13.00,negative likelihood ratio was 0.20,the diagnostic performance was better than APACHE-Ⅱ,Ranson and Marshall scoring systems and serum CRP concentration.Conclusions Human serum S100A12 levels elevated at early stage of AP.S100A12 ＞285.32 ng/ml represents high risk of SAP,which is more sensitive and accurate than APACHE-Ⅱ and Marshall scoring system.

Objective To understand the prevalence of mild cognitive impairment(MCI) and to compare the geographical distribution for the early prevention and treatment of disease,and to provide the reference basis for the establishment of related policies.Method Systematical search method and inclusion criterion were made and relative English and Chinese database such as China biology medicine disc (CBMdisc),China national knowledge infrastructure (CNKI),VIP database (VIP),WanFang,Pubmed,excerpta medica database (EMBASE),the cochrane library were searched.Tailored quality evaluation standard of epidemiological research was used to evaluate study quality for each included study.I2 was used to measure the heterogeneity between studies,and relevant model of meta-analysis and subgroup analysis were carried out to merger and analyze data.Subgroup analysis was used to explore heterogeneity.Results Overall,in the present 40 relevant articles were included.The quality assessment was good (median score was 15).Meta-analyses were conducted for 40 cross-sectional studies investigating the prevalence of MCI,the pooled prevalence of MCI was 14.5％ (95％CI 12.8％-16.2％).Subgroup results showed that in recent years,the prevalence rate has been gradually increased over time.There was a higher prevalence in those who were older.The prevalence rate of female were higher than that of male(16.0％(95％CI 14.2％-17.9％) vs.12.6％(95％CI 10.8％-14.4％)),rural were higher than that of urban (18.2％(95％CI 14.2％-22.1％) vs.13.6％ (95％ CI 11.9％-15.3％)).Prevalence was decreased while cultural level rising,and that of single (including single,divorce or live alone) elderly was higher than married people.Conclusion MCI in China have a high prevalence.Over the past decade,the prevalence and incidence of MCI were significantly affected by age,gender,education level,marital status,place of residence and other factors.

Objective To understand the prevalence of mild cognitive impairment(MCI) and to compare the geographical distribution for the early prevention and treatment of disease,and to provide the reference basis for the establishment of related policies.Method Systematical search method and inclusion criterion were made and relative English and Chinese database such as China biology medicine disc (CBMdisc),China national knowledge infrastructure (CNKI),VIP database (VIP),WanFang,Pubmed,excerpta medica database (EMBASE),the cochrane library were searched.Tailored quality evaluation standard of epidemiological research was used to evaluate study quality for each included study.I2 was used to measure the heterogeneity between studies,and relevant model of meta-analysis and subgroup analysis were carried out to merger and analyze data.Subgroup analysis was used to explore heterogeneity.Results Overall,in the present 40 relevant articles were included.The quality assessment was good (median score was 15).Meta-analyses were conducted for 40 cross-sectional studies investigating the prevalence of MCI,the pooled prevalence of MCI was 14.5％ (95％CI 12.8％-16.2％).Subgroup results showed that in recent years,the prevalence rate has been gradually increased over time.There was a higher prevalence in those who were older.The prevalence rate of female were higher than that of male(16.0％(95％CI 14.2％-17.9％) vs.12.6％(95％CI 10.8％-14.4％)),rural were higher than that of urban (18.2％(95％CI 14.2％-22.1％) vs.13.6％ (95％ CI 11.9％-15.3％)).Prevalence was decreased while cultural level rising,and that of single (including single,divorce or live alone) elderly was higher than married people.Conclusion MCI in China have a high prevalence.Over the past decade,the prevalence and incidence of MCI were significantly affected by age,gender,education level,marital status,place of residence and other factors.

Objective To study clinical effects and adverse reactions of hepatic artery intervention combining targeted therapy on hepatic metastasis of colonic carcinoma. Methods Eighty cases of patients with hepatic metastasis of colonic carcinoma, patients in the control group were selected, patients in the control group were subject to hepatic artery in-tervention therapy according to different methods of treatment , and patients in the observation group were subject to targeted therapy on the basis of that applied to patients in the control group , clinical effects and adverse reactions of patients in two groups were observed. Results The comparison in the total effective rate of patients in two groups (χ2=6.9520,P=0.0084), and the comparison in one-year survival rate of patients in two groups(χ2=4.7760,P=0.0289), the comparison in two-year survival rate of patients in two groups (χ2=5.6144,P=0.0178), the comparison in three-year survival rate of patients in two groups(χ2=4.3988,P=0.0360), and the comparison in five-year survival rate of patients in two groups (χ2=4.4443,P=0.0350), the differences were statistically significant. The comparison in adverse reaction of patients in two groups was not significantly different. Conclusion The hepatic artery intervention combining targeted therapy on hepatic metastasis of colonic carcinoma delivers great effect and significantly prolong the life of patients , being worthy of clinical application.

Objective To investigate the effects of back massage on chemotherapy-related fatigue and anxiety in cancer patients .Methods A total of 94 patients with pathology diagnosis of cancer from October 2013 to July 2014 were selected and divided into experimental group and control group on average by random number table.The control group had been given routine care while the patients in experimental groupreceived back message and routine care at the same time .In the first day of third circle chemotherapy , we compared fatigue score of Fatigue Self-assessment Scale (FSAS)and Self-Rating Anxiety Scale (SAS) between two groups, and recorded and analyzed the side effects such as nausea , vomiting and heart failure .Results The incidence of adverse reactions in the experimental group was less than that in the control group , the difference was statistically significant (P<0.05).Before intervention, FSAS and SAS score between the two groups had no significant differences [(42.6 ±6.8) vs (41.9 ±7.3),(52.8 ±9.3) vs (53.4 ±9.0);P>0.05)].After intervention, the scores of FSAS and SAS in experimental group were (35.2 ±4.7),(41.8 ±4.6), lower than the control group [(45.3 ±5.8),(59.4 ±7.1)], the differences were statistically significant (t =6.267,9.558;respectively;P<0.01).Fatigue and anxiety in the experimental group of patients after intervention decreased , while anxiety scores in the control group increased , the differences were statistically significant ( P <0.05). Conclusions The back massage treatments should be popularized due to reducing the incidence of adverse reactions , fatigue and anxiety , and increase comfort .