Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1β inflammatory axis.METHODS Fifty 4-week-old male Wistar rats were selected,10 of which were randomly selected as the control group,and the oth-er 40 were fed a high-salt and high-fat diet to establish an obese hypertension model.The rats with successful modeling(20 rats)were randomly divided into the model group,normal-dose Huangqin decoction group,high-dose Huangqin decoction group,and IL-1β in-hibitor group,with 5 rats in each group.From the 12th week,the normal-dose group was gavaged with Huangqin decoction 2.835 g·kg-1,the high-dose group was gavaged with Huangqin decoction 5.67 g·kg-1,and the IL-1β inhibitor group was intraper-itoneally injected with 1.5 mg·kg-1 AS101,3 times a week,for 8 weeks.The rats were weighed and blood was collected 12 h after the last administration,and the thoracic aorta and perivascular fat tissue were isolated.Serum inflammatory factors were detected,patho-logical changes were observed,eNOS expression was detected by immunofluorescence,and NEK7,NLRP3,Caspase-1,ASC,and IL-1β expression levels were detected by Western blot and qPCR.RESULTS The rats in the model group had a significant increase in body weight,an increase in the area of peritubular fat lipid droplets,and severe endothelial injury;systolic blood pressure,diastolic blood pressure,serum IL-1β,IL-6,and TNF-α were significantly elevated in the model group,and the expression of eNOS was sig-nificantly reduced,and the expression levels of NEK7,NLRP3,Caspase-1,ASC,and IL-1β proteins and mRNAs were significantly elevated.Compared with the model group,rats in the Huangqin decoction and IL-1β inhibitor groups had lower body weights,reduced endothelial damage,lower systolic and diastolic blood pressures,lower serum IL-1β,IL-6,and TNF-α,and higher eNOS expression.NEK7,NLRP3,Caspase-1,ASC and IL-1β protein expression was significantly reduced in the high dose group of Huan-gqin decoction and the IL-1β inhibitor group.In addition,Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner,with the effect being more pronounced in the high-dose group.CONCLUSION Huangqin de-coction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hyper-tension by regulating the NEK7-NLRP3/IL-1β inflammatory axis.

Objective To analyze adverse drug event(ADE)signals associated with exenatide based on data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS),and to provide insights for rational medication use in clinical settings.Methods ADE reports of exenatide as the primary suspected drug were obtained by collecting the data of FAERS database from the first quarter 2014 to the second quarter 2024.ADE signals were analyzed by joint reporting odds ratio(ROR)method,proportional reporting odds ratio(PRR)method,Bayesian confidence interval progressive neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,118 745 reports of exenatide-related ADEs were collected.These ADEs spanned 14 system-organ classes and involved 185 preferred terms.Commonly reported ADEs included reactions at the injection site,hypoglycemia,reduced appetite,and cholelithiasis.Severe ADEs were primarily cases of acute pancreatitis,in consistent with the drug's labeling.Moreover,the instructions did not record ADE signals of pancreatic cancer,thyroiditis,and reduced frustration tolerance.Conclusion Prescription of the exenatide should be vigilant about the signals not listed on the product labeling,such as pancreatic cancer,thyroid cancer,and decreased frustration tolerance,to improve the safety of medication use in patients.

Objective To mine adverse drug event(ADE)signals of pioglitazone,and to provide references for the safe clinical use of the medication.Methods The reporting odds ratio(ROR)method and the Bayesian confidence propagation neural network(BCPNN)method were utilized to analyze pioglitazone ADE reports from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,spanning from the first quarter of 2013 to the second quarter of 2024.Results After data cleaning,a total of 16 904 pioglitazone ADE reports were retrieved.The ADE reports primarily involved individuals over the age of 45,with a male predominance,and were mainly reported from the United States.After screening,180 ADE signals were identified,affecting 27 system-organ classes(SOC).Out of these,34 ADE signals were classified as medium to high risk,with 9 ADE signals not mentioned in the product labeling,including ureteral cancer,urethral cancer,gallbladder tumors,malignant tumors of the renal pelvis,pericardial tamponade,left ventricular dysfunction,pulmonary edema,cystitis,and somniloquy.Conclusion In addition to closely monitoring weight gain,systemic edema,and heart failure,clinical attention should be given to left ventricular dysfunction,pulmonary edema,cystitis,and pericardial tamponade ADEs that are not mentioned in the instructions,to ensure the safety of pioglitazone use in clinical practice.

Objective To investigate post-marketing adverse drug event(ADE)signals associated with lixisenatide,and to provide guidance for safe clinical use.Methods The ADE reporting data of lixisenatide ADE were mined and the signals were detected from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the first quarter 2013 to the second quarter 2024 using the reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method.Results After data cleaning,a total of 5 162 ADE reports with lixisenatide as the primary suspected drug were collected.The 85 ADE signals identified by the two statistical analysis methods,affected 14 system-organ classes(SOC).They were primarily concentrated in injuries,poisonings,and procedural complications(25.88％),various examinations(14.12％),systemic diseases and reactions at administration sites(14.12％),gastrointestinal diseases(9.41％),and various neurological diseases(5.88％).There were 28 ADE signals such as pancreatitis,visual impairment,and color blindness,that were not included in the drug instructions.Conclusion In addition to monitoring for common ADE associated with GLP-1 receptor agonists such as hypoglycemia,gastrointestinal,and neurological effects,clinicians should also be vigilant for underlying ADE like pancreatic-related diseases,eye toxicity reaction when using lixisenatide to ensure safe and rational medication use.

bjective To mine signals of post-marketing adverse drug events(ADEs)associated with dapagliflozin,and to provide insights for safe medication in clinical settings.Methods Data on ADEs related to dapagliflozin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024.The analyses involved data mining and signal monitoring using disproportionality analysis techniques including the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method,and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,a total of 55 832 qualified dapagliflozin case reports were obtained,involving 25 090 patients,with a slightly higher percentage of males(44.99％)than females(41.18％).The predominant age group was 45 to 64 years(20.78％).A total of 379 ADE signals were detected across 22 system-organ classes(SOC).The ADEs of dapagliflozin were mainly concentrated in the SOC such as infections and infestations,general disorders and administration sites conditions,and metabolism and nutrition disorders,aligning with information provided in the drug instructions.Additionally,the ADE signals were not documented in drug inserts such as scrotal gangrene,periperineal cellulitis,scrotal abscess,hyperglycemia,ketonuria,and pancreatitis.Conclusion When clinically using dapagliflozin,it is essential to conduct a thorough medication assessment.In addition to closely monitoring diabetes ketoacidosis,fungal infection,and acute renal injury.The latent ADEs that are not mentioned in the instructions to should be noticed ensure safe medication.

Objective To mine the real-world risk signals associated with saxagliptin-related adverse drug event(ADE),and to provide insights for evidence-based use of the drug in clinical practice.Methods Data on ADE related to saxagliptin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024,and analyzed using the reporting odds ratio(ROR)and Bayesian confidence propagation neural network(BCPNN)techniques.Results After data cleaning,the study analyzed 2 036 qualified case reports from patients who were using saxagliptin,uncovering 4 497 adverse events and identifying 131 adverse event signals across 19 system-organ classes(SOCs),including cardiac organ system diseases(20.61％),various types of investigations(10.69％),and gastrointestinal tract diseases(13.74％).Among them,heart failure,pancreatitis,pancreatic cancer,and hypoglycaemic coma were high-intensity signals.Conclusion In clinical practice,the indications for saxagliptin should be strictly managed.It is advisable to avoid using saxagliptin as monotherapy in patients with a history of heart failure or in patients at elevated risk for arteriosclerotic cardiovascular disease.Continuous monitoring of essential organ functions,especially cardiac and pancreatic,is essential throughout the course of treatment to ensure the safety of the medication.

Objective To analyze adverse drug event(ADE)signals associated with exenatide based on data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS),and to provide insights for rational medication use in clinical settings.Methods ADE reports of exenatide as the primary suspected drug were obtained by collecting the data of FAERS database from the first quarter 2014 to the second quarter 2024.ADE signals were analyzed by joint reporting odds ratio(ROR)method,proportional reporting odds ratio(PRR)method,Bayesian confidence interval progressive neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,118 745 reports of exenatide-related ADEs were collected.These ADEs spanned 14 system-organ classes and involved 185 preferred terms.Commonly reported ADEs included reactions at the injection site,hypoglycemia,reduced appetite,and cholelithiasis.Severe ADEs were primarily cases of acute pancreatitis,in consistent with the drug's labeling.Moreover,the instructions did not record ADE signals of pancreatic cancer,thyroiditis,and reduced frustration tolerance.Conclusion Prescription of the exenatide should be vigilant about the signals not listed on the product labeling,such as pancreatic cancer,thyroid cancer,and decreased frustration tolerance,to improve the safety of medication use in patients.

Objective To mine adverse drug event(ADE)signals of pioglitazone,and to provide references for the safe clinical use of the medication.Methods The reporting odds ratio(ROR)method and the Bayesian confidence propagation neural network(BCPNN)method were utilized to analyze pioglitazone ADE reports from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,spanning from the first quarter of 2013 to the second quarter of 2024.Results After data cleaning,a total of 16 904 pioglitazone ADE reports were retrieved.The ADE reports primarily involved individuals over the age of 45,with a male predominance,and were mainly reported from the United States.After screening,180 ADE signals were identified,affecting 27 system-organ classes(SOC).Out of these,34 ADE signals were classified as medium to high risk,with 9 ADE signals not mentioned in the product labeling,including ureteral cancer,urethral cancer,gallbladder tumors,malignant tumors of the renal pelvis,pericardial tamponade,left ventricular dysfunction,pulmonary edema,cystitis,and somniloquy.Conclusion In addition to closely monitoring weight gain,systemic edema,and heart failure,clinical attention should be given to left ventricular dysfunction,pulmonary edema,cystitis,and pericardial tamponade ADEs that are not mentioned in the instructions,to ensure the safety of pioglitazone use in clinical practice.