AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

By collecting inspection results from medical device clinical trials from 2016 to 2023,to analyze and discuss common problems of clinical trials from both in vitro diagnostic reagents and medical devices,and propose the suggested mea-sures taken by participants in the clinical trial,so as to avoid similar problems occur and ensure the quality of clinical trials.

This paper analyzes the characteristics of highly cited papers published in Chinese Clinical Pharmacology and Therapeutics in the past ten years,in order to explore the influence and re-search value of these papers.Highly cited papers are an important index to evaluate the scientific re-search level of scholars and research institutions,so this study focuses on the characteristics of their number,citation frequency,number of co-authors and regional distribution.The paper uses bibliomet-rics to analyze the publication trend and citations of highly cited papers.The results show that during the observation period,the number of highly cited papers decreases year by year,and there is a signifi-cant correlation between cited frequency and publi-cation time.In addition,the number of co-authors presents a normal distribution,among which the number of co-authors is the largest,indicating that moderate cooperation has a positive effect on the influence of papers.From the perspective of geo-graphical distribution,the author group of the mag-azine is relatively dispersed,covering many regions of the country,among which Anhui,Hunan and Zhejiang have become the main sources of high-quality manuscripts.The finding reflects the maga-zine's wide reach across the country.The results of this study provide empirical support for under-standing the characteristics of highly cited papers and emphasize the importance of research collabo-ration and geographical factors in research publica-tion.Through the analysis of highly cited papers,this paper provides references for subsequent re-searchers in selecting research topics and coopera-tion methods,and also provides beneficial sugges-tions for improving the research level and influence of clinical pharmacology in China.

AIM:To investigate the effects of Nrf1 on neuronal apoptosis treated by oxygen-glucose deprivation/reperfusion and the mechanism.METHODS:Single-cell sequencing data was ana-lyzed by GEO database,and the correlation of Nrf1 expression with apoptotic pathways evaluated based on GSVA package calculations.PC12 cells and primary neurons were divided into the Normal group,the OGD/R group,the OGD/R+siRNA-NC group,and the OGD/R+Nrf1-siRNA-2 group.Cell images was observed by laser scanning confocal mi-croscopy;the viability of cells were detected by MTT assay;the apoptosis of cells were detected by flow cytometry;DHE fluorescent probe to detect ROS levels,the protein expression of Nrf1,bcl-2 and Bax were detected by Western blot;and nuclear translocation was observed by laser scanning confo-cal microscope.RESULTS:The results of biosigna-ture analysis revealed that Nrf1 was mainly en-riched in the apoptotic pathway;compared with normal group,the cell body became smaller,syn-apse broke,cells clustered in PC12 cells and prima-ry neurons with OGD/R treated,and the vitality of PC12 cells and neuronal were decreased significant-ly(P＜0.01);ROS levels were significantly higher(P＜0.01),the expressions of Nrf1 and Bax were in-creased significantly,and the expression of bcl-2 was decreased significantly(P＜0.05).Compared with the OGD/R group,there was no significant dif-ference in the siRNA-NC group;compared with the siRNA-NC group,the viability of cells was de-creased significantly(P＜0.01);ROS levels were sig-nificantly increased(P＜0.01),the expressions of Nrf1 and Bax were increased markedly,and the ex-pressions of bcl-2 was decreased significantly(P＜0.05)in Nrf1-siRNA-2 group.CONCLUSION:Nrf1 at-tenuates neuronal injury caused by oxygen glucose deprivation/reperfusion via inhibiting apoptosis.

AIM:To explore the regulatory mecha-nism of pinoresinol diglucoside(PDG)on angiogen-esis during osteoporotic fracture healing in vivo and in vitro.METHODS:Fifty male C57BL/6J mice were randomly divided into five groups:normal group,model group,PDG 0.005,0.015 g/kg groups,and parathyroid hormone 1-34(PTH1-34)4×10-5 g/kg group.The osteoporotic fracture model of ovariec-tomized combined with femoral fracture was estab-lished,the PDG group was given intragastric admin-istration every other day and the PTH1-34 group was given subcutaneous injection of PTH1-34 every other day for 8 weeks.Micro-CT scanning,immunofluo-rescence and immunohistochemical staining were used to detect the related parameters and protein expressions.Human umbilical vein endothelial cells(HUVECs)were cultured,normal group,PDG 1,10,100 μmol/L groups and PTH1-341 ng/mL group were set up.CCK-8 assay,scratch experiment,tubule for-mation experiment,immunofluorescence and Western blot were used to detect the related pa-rameters and protein expressions.RESULTS:In vivo experiments found,compared with the normal con-trol group,a small amount of bone callus volume of fracture site were increased in the model control group,while BMD of non-callus site of femur,tra-becular bone fraction(BV/TV),trabecular thickness(Tb.Th)and trabecular number(Tb.N)were de-creased(P＜0.01),and trabecular separation(Tb.Sp)was increased(P＜0.01).The positive expression of vascular endothelial marker vascular endothelial markers(CD31)was decreased(P＜0.01).Compared with mice in the model control group,bone callus volume,index of BMD and BV/TV were increased in the PDG 0.005 g/kg group(P＜0.05),index of BMD,BV/TV,Tb.Th,Tb.N were increased,and index of Tb.Sp was decreased in the PDG 0.015 g/kg group(P＜0.05),the positive expression of CD31 was in-creased in the PDG administration groups(P＜0.01),the protein expressions of vascular endothelial growth factor(VEGF-A)(P＜0.01),Yes-associated protein 1(YAP1)(P＜0.01),PDZ-binding motif(TAZ)(P＜0.05)and TEA domain transcription factor 2(TEAD2)(P＜0.01)were increased in callus in the PDG 0.015 g/kg groups.Cell experiments found,compared with the normal control group,PDG groups promoted the proliferation,migration and tubule formation activity of HUVECs to varying de-grees(P＜0.05),at the same time,the expression of endothelial cadherin(E-cadherin)was decreased(P＜0.01),and VEGF-A,TEAD2,TAZ and YAP1 protein expression were increased(P＜0.05).CONCLUSION:PDG may accelerate osteoporotic fracture healing by promoting bone angiogenesis through regulat-ing Hippo signal pathway.

AIM:To observe the effect of opioid-free anesthesia with esketamine on delirium after hip replacement surgery in elderly patients.METH-ODS:One hundred and fourteen elderly patients who underwent hip replacement were randomly di-vided into two groups:opioid-free anesthesia(OFA)group and opioid anesthesia(OA)group(n=57).During anesthesia induction and maintenance,es-ketamine was administered in OFA group,and that fentanyl and remifentanil were administered in OA group.Delirium was mainly recorded within 3 days after the surgeries,and the patients'delirium sta-tus was evaluated using the Chinese Revised Deliri-um Diagnostic Scale(CAM-CR).RESULTS:The pa-tients in OFA group had lower CAM-CR scores and delirium incidence compared to those in the OA group at 2 days after surgery.CONCLUSION:Opioid-free anesthesia based on esketamine can effective-ly reduce delirium after hip replacement in elderly patients.

Arterial thrombosis is a major cause of death in several cardiovascular diseases(CVDs),including coronary heart disease and stroke.Since platelets play a pivotal role in arterial thrombosis,antiplatelet drug is an important part of the clinical therapy of CVD patients.Currently,the long-term antithrombotic effect of the dual antiplatelet thera-py of P2Y12 antagonists combined with aspirin are showed to be effective.And αⅡbβ3 antagonists rep-resented by tirofiban are widely used for antiplate-let therapy in emergency surgery.However,the bleeding risk caused by antiplatelet therapy is a clinical issue that cannot be ignored.In order to provide a reference for further research on anti-platelet drugs,this article reviews the major tar-gets of antiplatelet drugs and the drugs that have been under clinical research in recent years.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Sepsis poses a significant threat to hu-man health due to its widespread prevalence,high mortality rate,substantial treatment costs,and the absence of effective life-saving therapies.Melato-nin,a primary hormone regulating the circadian rhythm,has demonstrated potential as a promising therapeutic agent against sepsis.Its anti-inflamma-tory,antioxidant,immunomodulatory,mitochondri-al protective,and multi-organ protective effects are noteworthy.In this review,we summarize current research on the mechanisms of action and clinical efficacy of melatonin in sepsis treatment and multi-organ function preservation,aiming to offer new perspectives and support for sepsis research and therapy.

AIM:To exploring the mechanism of Xin Mai Jia(XMJ)in inhibiting hypertensive cardiac hypertrophy through network pharmacology and animal experiments.METHODS:Retrieving the ac-tive ingredients and target points of XMJ by search-ing the TCMSP database and related literature re-ports;using the Gene Cards,OMIM,and Drug Bank databases to screen targets for hypertensive cardi-ac hypertrophy;constructing a network of tradi-tional Chinese medicine-active ingredients-poten-tial targets and a protein-protein interaction(PPI)network;using DAVID software for target gene on-tology(GO)functional enrichment analysis and Kyo-to Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis;using Auto Dock soft-ware for molecular docking.A spontaneously hy-pertensive rat(SHR)model was established,and hematoxylin-eosin(HE)staining was used to detect the morphology of cardiac tissue and cellular hy-pertrophy,Masson staining was used to detect col-lagen deposition in cardiac tissue,and Western blot to detect the expression of heat shock protein(HSP90AA1),mammalian target of rapamycin(mTOR),peroxisome proliferator-activated receptor y(PPARG),and tumor necrosis factor(TNF-α)in car-diac tissue.RESULTS:A total of 56 potential active ingredients were identified in XMJ,and 5,492 tar-gets related to hypertensive cardiac hypertrophy were obtained.The targets in the core network were ranked according to their Degree values,and four main targets were selected:HSP90AA1,mTOR,PPARG,and TNF-α.The results of HE staining showed that compared with the normal group,the average area of cardiomyocytes in the SHR group increased significantly(P＜0.05),while there was no significant change in the XMJ group.The hypertro-phy in the SHR+XMJ group was significantly alleviat-ed(P＜0.05).The results of Masson staining showed that compared with the normal group,the levels of interstitial fibrosis and perivascular fibrosis in the SHR group rats increased significantly(P＜0.01),and XMJ could significantly reduce the fibrosis levels in the SHR group rats(P＜0.01).The results of Western blot showed that compared with the normal group rats,the expression of HSP90AA1 and PPARG in the myocardial tissue of SHR group rats was downregu-lated,mTOR phosphorylation was downregulated,and TNF-α was significantly upregulated(P＜0.01).In the SHR+XMJ group,the expression of HSP90AA1,PPARG,and TNF-α in the myocardial tis-sue of rats returned to normal levels,and mTOR phosphorylation returned to normal levels.In the XMJ group,there were no significant changes in the above indicators compared with the normal group rats.CONCLUSION:The mechanism underly-ing the inhibitory effect of XMJ on myocardial cell hypertrophy in hypertension involves a comprehen-sive action through multiple components,multiple targets,and multiple pathways.