As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective:To evaluate the clinical efficacy of endoclip papillaplasty (ECPP) for preventing recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on 1 941 patients who underwent ERCP for choledocholithiasis in Henan Provincial People's Hospital from January 2019 to December 2023. A total of 250 patients who received ECPP were assigned to the ECPP group, while 251 matched controls were selected via 1∶1 year-stratified sampling into the control group. After follow-up, 209 ECPP cases and 190 controls were ultimately included in the analysis. Stone removal success rate, incidence of perioperative complications, and postoperative choledocholithiasis recurrence were compared between the two groups. Univariate and multivariate logistic regression were used to determine the risk factors for choledocholithiasis recurrence after ERCP.Results:Both groups achieved 100.0% stone removal success rate. There was no significant difference in the incidence of intraoperative perforation [0.5% (1/209) VS 1.1% (2/190), χ2=0.01, P=0.934], postoperative hyperamylasemia [21.5% (45/209) VS 17.4% (33/190), χ2=1.10, P=0.295] or post-ERCP pancreatitis [3.8% (8/209) VS 8.1% (9/190), χ2=0.20, P=0.653] between the ECPP group and the control group. The ECPP group showed significantly lower bleeding rate [5.1% (11/209) VS 12.3% (23/190), χ2=5.98, P=0.014] and choledocholithiasis recurrence rate [10.5% (22/209) VS 18.9% (36/190), χ2=5.68, P=0.017] compared with the control group. The multivariate logistic regression identified dilated common bile duct diameter ( OR=1.881, 95% CI: 1.101-3.213, P=0.021) as an independent risk factor for choledocholithiasis recurrence, while being female ( OR=0.482, 95% CI: 0.266-0.875, P=0.016) and ECPP ( OR=0.497, 95% CI:0.278-0.887, P=0.018) were protective factors. Conclusion:ECPP effectively reduces choledocholithiasis recurrence rate and bleeding risk after ERCP. ECPP and being female serve as protective factors for choledocholithiasis recurrence, while dilated bile duct diameter is an independent risk factor.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective:To evaluate the clinical efficacy of endoclip papillaplasty (ECPP) for preventing recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on 1 941 patients who underwent ERCP for choledocholithiasis in Henan Provincial People's Hospital from January 2019 to December 2023. A total of 250 patients who received ECPP were assigned to the ECPP group, while 251 matched controls were selected via 1∶1 year-stratified sampling into the control group. After follow-up, 209 ECPP cases and 190 controls were ultimately included in the analysis. Stone removal success rate, incidence of perioperative complications, and postoperative choledocholithiasis recurrence were compared between the two groups. Univariate and multivariate logistic regression were used to determine the risk factors for choledocholithiasis recurrence after ERCP.Results:Both groups achieved 100.0% stone removal success rate. There was no significant difference in the incidence of intraoperative perforation [0.5% (1/209) VS 1.1% (2/190), χ2=0.01, P=0.934], postoperative hyperamylasemia [21.5% (45/209) VS 17.4% (33/190), χ2=1.10, P=0.295] or post-ERCP pancreatitis [3.8% (8/209) VS 8.1% (9/190), χ2=0.20, P=0.653] between the ECPP group and the control group. The ECPP group showed significantly lower bleeding rate [5.1% (11/209) VS 12.3% (23/190), χ2=5.98, P=0.014] and choledocholithiasis recurrence rate [10.5% (22/209) VS 18.9% (36/190), χ2=5.68, P=0.017] compared with the control group. The multivariate logistic regression identified dilated common bile duct diameter ( OR=1.881, 95% CI: 1.101-3.213, P=0.021) as an independent risk factor for choledocholithiasis recurrence, while being female ( OR=0.482, 95% CI: 0.266-0.875, P=0.016) and ECPP ( OR=0.497, 95% CI:0.278-0.887, P=0.018) were protective factors. Conclusion:ECPP effectively reduces choledocholithiasis recurrence rate and bleeding risk after ERCP. ECPP and being female serve as protective factors for choledocholithiasis recurrence, while dilated bile duct diameter is an independent risk factor.

Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P＜0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P＜0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

As a long-standing research focus in electroanalytic chemistry,electrochemical biosensors have attracted immense interest in detection of biological targets such as small molecules,proteins,enzymes,nucleic acids,exosomes,circulating tumor cells (CTCs),bacteria,and viruses. etc. The highly sensitive and selective electrochemical detection of biological targets relies on the use of the specific biorecognition elements (BREs) and efficient signal amplification strategies. In this review,the typically used BREs and amplification strategies in electrochemical biosensing were summarized. On the basis of the interactions between BREs and targets,the enzyme/substrate-based and receptor/ligand-based electrochemical biosensors were first introduced,focusing on the BREs used in the electrochemical detection of nucleic acid targets and non-nucleic acid targets. Then,the representative use of various isothermal nucleic acid amplification technologies,catalytic reactions,functionalized nanocarriers,and polymer materials in amplified electrochemical detection of biological targets were introduced. The challenges with respect to the practical use of electrochemical biosensors and the prospect of electrochemical biosensing were discussed.

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.