Pharmacoepidemiology is an interdisciplinary field that applies epidemiological methods to study drug use,effectiveness,and associated risk in populations.Standardizing research methods in this field is crucial for ensuring research quality and promote the development of the discipline.Based on the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition),this article interprets the relevant contents about classic research types and their derivative designs.It aims to clarify the types of study methodological designs in pharmacoepidemiology,systematically describe the characteristics and applications classical derivative designs,and compare these with research design frameworks outlined in international pharmacoepidemiological guidelines.Compared to the first edition,the second edition of the guideline has updated and detailed the types of research,updating the research design to original research(interventional research and non-interventional research),secondary research(systematic review,Meta-analysis,economic analysis,etc.),and tertiary research(umbrella review,etc.).Additionally,a variety of derivative designs have been added,including target trial emulation,nested case-control and case-cohort studies,case-crossover designs,self-controlled case series and self-controlled risk interval designs,case-population studies,interrupted time-series analysis,and case-coverage(ecological)designs for vaccine surveillance.This article strengthens the operability of the theoretical guidance of pharmacoepidemiological research methods in practice and provides a reference for conducting high-quality pharmacoepidemiological research.

Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.

Objective To explore the predictive value of the atherogenic index of plasma(AIP),triglyceride-glucose(TyG)index,and cerebral small vascular disease(CSVD)imaging load score regarding the early prognosis of patients with acute ischemic stroke(AIS)after intravenous thrombolysis.Methods A total of 379 inpatients diagnosed with AIS at the Shengli Oilfield Central Hospital and treated with intravenous thrombolysis from January 2022 to December 2023 were retrospectively analyzed.Relevant data were collected,and the CSVD imaging load score was evaluated.The patients were classified into the good prognosis group(≥18％)and the poor prognosis group(＜18％)based on the early neurological improvement rate 14 d after thrombolysis.An investigation into the independent risk factors influencing the early prognostic outcomes in patients suffering from AIS was conducted utilizing binary Logistic regression analysis.The efficacy of early prognosis prediction in patients undergoing intravenous thrombolysis was assessed through receiver operating characteristic(ROC)curve analysis.Results Systolic blood pressure,AIP,TyG index,neutrophil to lymphocyte ratio(NLR),cerebral microbleeds(CMB),enlarged perivascular spaces(EPVS)and a CSVD imaging load score of 2 points or higher served as independent risk factors influencing the early prognosis in AIS patients undergoing thrombolysis.The ROC curve analysis revealed that the area under the curve(AUC)for the CSVD imaging load score was 0.821,with a sensitivity of 80.4％and a specificity of 74％.The AUC of the AIP was 0.951,with a sensitivity of 89.2％and a specificity of 91.7％.The AUC of the TyG index was 0.918,with a sensitivity of 93.1％and a specificity of 82.7％.Conclusions The AIP,TyG index,and CSVD imaging load score serve as efficacious indicators in assessing the premature prognostication of AIS patients who underwent subsequently to intravenous thrombolytic therapy.

Pharmacoepidemiology is an interdisciplinary field that applies epidemiological methods to study drug use,effectiveness,and associated risk in populations.Standardizing research methods in this field is crucial for ensuring research quality and promote the development of the discipline.Based on the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition),this article interprets the relevant contents about classic research types and their derivative designs.It aims to clarify the types of study methodological designs in pharmacoepidemiology,systematically describe the characteristics and applications classical derivative designs,and compare these with research design frameworks outlined in international pharmacoepidemiological guidelines.Compared to the first edition,the second edition of the guideline has updated and detailed the types of research,updating the research design to original research(interventional research and non-interventional research),secondary research(systematic review,Meta-analysis,economic analysis,etc.),and tertiary research(umbrella review,etc.).Additionally,a variety of derivative designs have been added,including target trial emulation,nested case-control and case-cohort studies,case-crossover designs,self-controlled case series and self-controlled risk interval designs,case-population studies,interrupted time-series analysis,and case-coverage(ecological)designs for vaccine surveillance.This article strengthens the operability of the theoretical guidance of pharmacoepidemiological research methods in practice and provides a reference for conducting high-quality pharmacoepidemiological research.

Objective To explore the predictive value of the atherogenic index of plasma(AIP),triglyceride-glucose(TyG)index,and cerebral small vascular disease(CSVD)imaging load score regarding the early prognosis of patients with acute ischemic stroke(AIS)after intravenous thrombolysis.Methods A total of 379 inpatients diagnosed with AIS at the Shengli Oilfield Central Hospital and treated with intravenous thrombolysis from January 2022 to December 2023 were retrospectively analyzed.Relevant data were collected,and the CSVD imaging load score was evaluated.The patients were classified into the good prognosis group(≥18％)and the poor prognosis group(＜18％)based on the early neurological improvement rate 14 d after thrombolysis.An investigation into the independent risk factors influencing the early prognostic outcomes in patients suffering from AIS was conducted utilizing binary Logistic regression analysis.The efficacy of early prognosis prediction in patients undergoing intravenous thrombolysis was assessed through receiver operating characteristic(ROC)curve analysis.Results Systolic blood pressure,AIP,TyG index,neutrophil to lymphocyte ratio(NLR),cerebral microbleeds(CMB),enlarged perivascular spaces(EPVS)and a CSVD imaging load score of 2 points or higher served as independent risk factors influencing the early prognosis in AIS patients undergoing thrombolysis.The ROC curve analysis revealed that the area under the curve(AUC)for the CSVD imaging load score was 0.821,with a sensitivity of 80.4％and a specificity of 74％.The AUC of the AIP was 0.951,with a sensitivity of 89.2％and a specificity of 91.7％.The AUC of the TyG index was 0.918,with a sensitivity of 93.1％and a specificity of 82.7％.Conclusions The AIP,TyG index,and CSVD imaging load score serve as efficacious indicators in assessing the premature prognostication of AIS patients who underwent subsequently to intravenous thrombolytic therapy.

Objective:To investigate the expression of cancer-associated fibroblasts(CAFs) marker proteins in papillary thyroid carcinoma(PTC) using immunohistochemistry and explore their correlation with clinicopathological characteristics.Methods:The clinicopathological data of 90 PTC patients at Tianjin Medical University General Hospital from December 2019 to January 2021 were retrospectively analyzed. Surgical pathological cancer tissue samples were selected for immunohistochemical staining, and control group tissues were obtained from normal thyroid tissue adjacent to the tumor lesion. Four CAFs marker proteins, including fibroblast-activated protein(FAP), α-smooth muscle actin(α-SMA), Vimentin, and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored, followed by statistical analysis.Results:The immunoreactivity score of the CAFs marker proteins were correlated with extrathyroid invasion, lymph node metastasis, and multi-focality of PTC. FAP and α-SMA demonstrated better performance in this regard. Multivariate logistic regression analysis and receiver operating characteristic(ROC) curve analysis showed that high immunoreactivity scores of FAP and α-SMA were risk factors for poor clinical pathological features, with good predictive sensitivity and accuracy.Conclusion:Strong expression of CAFs was the risk factor for extrathyroid invasion, lymph node metastasis, and mutli-focality of PTC. FAP has the highest clinical value compared with other CAFs marker proteins.

Objective:To investigate the safety and effectiveness of the laparoscopic hepatectomy guided by three-dimensional visualization technology for treating hepatolithiasis in military flying personnel and to discuss the aeromedical assessment.Methods:The diagnosis and treatment of a military flying personnel with hepatolithiasis admitted to the Air Force Medical Center in December of 2021 and the conclusions of aeromedical assessment were analyzed. The literature was reviewed in combination with the progress of new technologies.Results:This case, a 40-year-old male helicopter aerial machinist, had been found gallbladder stones for 12 years, hepatolithiasis for 8 years, and intermittent right upper abdominal pain for more than 3 months. Ultrasound and CT examination showed multiple gallbladder stones, intrahepatic bile duct stones in the right posterior lobe of the liver with bile duct dilatation. Under the guidance of three-dimensional visualization technology, laparoscopic liver segment 6 precise resection, cholecystectomy, common bile duct exploration and stone removal, and T-tube drainage were performed. The patient was well recovered and waivered to flight after 6 months of the operation. As of the submission date, he has safely flown for 50 h.Conclusions:Laparoscopic anatomical hepatectomy guided by three-dimensional visualization technology in the military flying personnel with hepatolithiasis shows good safety and effect, and those who recover well after surgery can be waivered to flight.

Objective:To investigate the safety and effectiveness of the laparoscopic hepatectomy guided by three-dimensional visualization technology for treating hepatolithiasis in military flying personnel and to discuss the aeromedical assessment.Methods:The diagnosis and treatment of a military flying personnel with hepatolithiasis admitted to the Air Force Medical Center in December of 2021 and the conclusions of aeromedical assessment were analyzed. The literature was reviewed in combination with the progress of new technologies.Results:This case, a 40-year-old male helicopter aerial machinist, had been found gallbladder stones for 12 years, hepatolithiasis for 8 years, and intermittent right upper abdominal pain for more than 3 months. Ultrasound and CT examination showed multiple gallbladder stones, intrahepatic bile duct stones in the right posterior lobe of the liver with bile duct dilatation. Under the guidance of three-dimensional visualization technology, laparoscopic liver segment 6 precise resection, cholecystectomy, common bile duct exploration and stone removal, and T-tube drainage were performed. The patient was well recovered and waivered to flight after 6 months of the operation. As of the submission date, he has safely flown for 50 h.Conclusions:Laparoscopic anatomical hepatectomy guided by three-dimensional visualization technology in the military flying personnel with hepatolithiasis shows good safety and effect, and those who recover well after surgery can be waivered to flight.

Hepatocellular carcinoma is one of the malignant tumors with highest mortality.Nuclear factor κB (NF-κB) as the mediator of many pathways,such as metabolic pathway,angiogenesis and adherence factor,is implicated in the onset and progression of hepatocellular carcinoma.Through the literature retrieval,the activity of NF-κB and its implication in the onset,progression,invasion and metastasis have been reviewed in the article.

Objective Fluctuation of glucose levels is more likely to cause oxidative stress which contributes to the development of insulin resistance through activating c-Jun N-terminal kinase (JNK).Such antio xidants as vitamin C or vitamin E do not appear very helpful.Radix Astragali (RA) is an herbal medicine with antioxidative ability.The study was to explore whether RA would lower the risk of insulin resistance in diabetic rats.Methods Diabetic rats received RA,insulin or both RA and insulin after diabetes were induced in male Wistar rats.Serum levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNFα),advanced glycation endproducts(AGEs) levels in kidney,the expression of insulin receptor (IR),insulin receptor substrate 1 (IRS-1),p38 mitogen-activated protein kinase (MAPK),p-p38 MAPK,p-JNK,p-IRS-1 Ser307,and p-IRS-1 Tyr612 in skeletal muscles were determined.Results Compared to diabetic rats treated with insulin,the diabetic rats treated with both insulin and RA demonstrated significantly lower levels of IL-6,TNF-α and AGEs (P ＜ 0.05),significantly lower activation of p-p38 MAPK and JNK (P ＜0.05),significantly higher expressions of IRS-1 (P ＜0.05),p-IRS-1 Tyr612,and significantly lower expression of p-IRS-1 Ser307 (P ＜ 0.05).Conclusions RA can lower the risk of insulin resistance through fighting oxidative stress in diabetic rats.