High-quality clinical research represents the scientific foundation for generating credible medical evidence， guiding evidence-based practice， and optimizing public health strategies. The responsible conduct of research by clinical researchers serves as the core guarantee of research quality. Any act of research misconduct will not only result in the waste of research resources and damage the reputation of relevant individuals and institutions， but also undermine the validity of research evidence， mislead evidence-based medical practice， raise risks for public health decision-making， and ultimately impede the progress of medical innovation. Based on the framework of reinforcement theory， this paper elaborated on the internal correlation between reinforcement theory and the shaping of responsible conduct of research among clinical researchers， and demonstrated the necessity of shaping responsible conduct of research in the new context. It also summarized practical challenges encountered in such shaping， such as utilitarian-oriented research evaluation， complex conflicts of interest， inadequate review and supervision， constrained research resources， and insufficient education on responsible conduct of research. It further proposed countermeasures that were conducive to shaping the responsible research conduct of clinical researchers. These encompassed reconstructing the orientation of performance evaluation， dynamically managing risks arising from conflicts of interest， implementing precise constraints via ethical supervision， arranging tiered resource support， and internalizing cultural recognition of responsible research conduct.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

Objective To explore the efficacy of magnetic resonance angiography(MRA)combined with CXC motif chemokine ligand 12(CXCL12)in predicting ischemic stroke in patients with transient ischemic attack(TIA).Methods A total of 225 patients with TIA were selected,and all patients underwent MRA and CXCL12 examination before treatment.The occurrence of ischemic stroke in TIA patients was counted within 1 week of treatment,the factors influencing the occurrence of ischemic stroke in TIA patients were analyzed,and the value of MRA combined with CXCL12 in predicting the occurrence of ischemic stroke in TIA patients was ana-lyzed.Results Among the 225 patients,21 of them had ischemic stroke.Multivariate logistic regression analysis showed that Essen stroke risk scale(ESRS)score,lesion site stenosis,and CXCL12 level were the factors influencing the occurrence of ischemic stroke in TIA patients(P<0.05).The receiver operating characteristic(ROC)curve showed that the sensitivity of lesion site stenosis,CXCL12 and their combination in predicting the occurrence of ischemic stroke in TIA patients was 76.19%,71.43%,and 85.71%,respectively,the specificity was 80.39%,70.10%,and 88.73%,respectively,and the area under the curve(AUC)was 0.798,0.733,and 0.895,respectively.Conclusion MRA combined with CXCL12 has good efficacy in predicting the occurrence of ischemic stroke in TIA patients.

Objective:To explore the value of immature platelets and thromboelastography (TEG) in evaluating bleeding tendency in patients bitten by blood venomous snakes.Methods:In December 2023, a bleeding scoring system was used to grade the bleeding score and degree of bleeding in 147 patients with blood venomous snake bites. Immature platelets and TEG were also tested to analyze the correlation between the bleeding degree of patients and indicators such as TEG, immature platelet ratio (IPF), and absolute value of immature platelets (A-IPF). The measurement data were represented by Mean±SD, and ANOVA was used for comparison among groups. Statistical data were analyzed using χ2 test. Spearman correlation was used to analyze the correlation between bleeding degree and the platelet count (PLT), immature platelet and TEG. Pearson linear correlation was used to analyze the correlation of PLT, immature platelets and TEG. The indexes of immature platelets and TEG were analyzed by receiver operating characteristic curve. Results:The 147 patients were graded for bleeding severity based on their bleeding scores, and divided into mild (22 cases), moderate (119 cases), and severe groups (6 cases), and the clinical data such as age, gender and the time from bite to visit were compared among the three groups. The differences were not statistically significant ( P>0.05). The coagulation reaction time (R), clot formation time (K), and immature platelet parameters (IPF, A-IPF) in TEG parameters increased with the degree of bleeding. PLT decreased with the degree of bleeding, and the difference was statistically significant ( P<0.05). Blood venomous snake bite patients have a negative correlation between PLT and IPF ( r=-0.301, P=0.012), but no correlation with A-IPF ( r=0.072, P=0.461) ; PLT was positively correlated with coagulation Angle (αAngle) and maximum thrombus amplitude (MA) of TEG ( r=0.220、0.243, P=0.028、0.015), but negatively correlated with R value and K value ( r=-0.368、-0.362, P<0.001). IPF is positively correlated with R and K values ( r=303、271, P=0.0020、0.035) ; IPF is not correlated with MA value and Angle angle, while A-IPF is positively correlated with R value ( r=0.162, P<0.001). The degree of bleeding in patients is positively correlated with R value ( r=0.237, P<0.001), but not with K value, MA value, and Angle angle ( P>0.05) ; The degree of bleeding in patients is correlated with PLT ( r=-0.411, P<0.001). The ROC curve analysis results show that the R value, K value, and MA value are effective in evaluating the bleeding risk of blood venomous snake bites in patients, and the PLT combined with A-IPF has the best efficacy in evaluating the bleeding risk of blood venomous snake bites in patients. Conclusion:The combination of PLT and A-IPF, TEG's R value, K value, MA value indicators can accurately evaluate the bleeding risk of blood venomous snake bites, and can be widely used in clinical practice as an important prediction method for bleeding tendency in patients bitten by blood venomous snakes.

Objective To explore the efficacy of magnetic resonance angiography(MRA)combined with CXC motif chemokine ligand 12(CXCL12)in predicting ischemic stroke in patients with transient ischemic attack(TIA).Methods A total of 225 patients with TIA were selected,and all patients underwent MRA and CXCL12 examination before treatment.The occurrence of ischemic stroke in TIA patients was counted within 1 week of treatment,the factors influencing the occurrence of ischemic stroke in TIA patients were analyzed,and the value of MRA combined with CXCL12 in predicting the occurrence of ischemic stroke in TIA patients was ana-lyzed.Results Among the 225 patients,21 of them had ischemic stroke.Multivariate logistic regression analysis showed that Essen stroke risk scale(ESRS)score,lesion site stenosis,and CXCL12 level were the factors influencing the occurrence of ischemic stroke in TIA patients(P<0.05).The receiver operating characteristic(ROC)curve showed that the sensitivity of lesion site stenosis,CXCL12 and their combination in predicting the occurrence of ischemic stroke in TIA patients was 76.19%,71.43%,and 85.71%,respectively,the specificity was 80.39%,70.10%,and 88.73%,respectively,and the area under the curve(AUC)was 0.798,0.733,and 0.895,respectively.Conclusion MRA combined with CXCL12 has good efficacy in predicting the occurrence of ischemic stroke in TIA patients.

Objective:To explore the value of immature platelets and thromboelastography (TEG) in evaluating bleeding tendency in patients bitten by blood venomous snakes.Methods:In December 2023, a bleeding scoring system was used to grade the bleeding score and degree of bleeding in 147 patients with blood venomous snake bites. Immature platelets and TEG were also tested to analyze the correlation between the bleeding degree of patients and indicators such as TEG, immature platelet ratio (IPF), and absolute value of immature platelets (A-IPF). The measurement data were represented by Mean±SD, and ANOVA was used for comparison among groups. Statistical data were analyzed using χ2 test. Spearman correlation was used to analyze the correlation between bleeding degree and the platelet count (PLT), immature platelet and TEG. Pearson linear correlation was used to analyze the correlation of PLT, immature platelets and TEG. The indexes of immature platelets and TEG were analyzed by receiver operating characteristic curve. Results:The 147 patients were graded for bleeding severity based on their bleeding scores, and divided into mild (22 cases), moderate (119 cases), and severe groups (6 cases), and the clinical data such as age, gender and the time from bite to visit were compared among the three groups. The differences were not statistically significant ( P>0.05). The coagulation reaction time (R), clot formation time (K), and immature platelet parameters (IPF, A-IPF) in TEG parameters increased with the degree of bleeding. PLT decreased with the degree of bleeding, and the difference was statistically significant ( P<0.05). Blood venomous snake bite patients have a negative correlation between PLT and IPF ( r=-0.301, P=0.012), but no correlation with A-IPF ( r=0.072, P=0.461) ; PLT was positively correlated with coagulation Angle (αAngle) and maximum thrombus amplitude (MA) of TEG ( r=0.220、0.243, P=0.028、0.015), but negatively correlated with R value and K value ( r=-0.368、-0.362, P<0.001). IPF is positively correlated with R and K values ( r=303、271, P=0.0020、0.035) ; IPF is not correlated with MA value and Angle angle, while A-IPF is positively correlated with R value ( r=0.162, P<0.001). The degree of bleeding in patients is positively correlated with R value ( r=0.237, P<0.001), but not with K value, MA value, and Angle angle ( P>0.05) ; The degree of bleeding in patients is correlated with PLT ( r=-0.411, P<0.001). The ROC curve analysis results show that the R value, K value, and MA value are effective in evaluating the bleeding risk of blood venomous snake bites in patients, and the PLT combined with A-IPF has the best efficacy in evaluating the bleeding risk of blood venomous snake bites in patients. Conclusion:The combination of PLT and A-IPF, TEG's R value, K value, MA value indicators can accurately evaluate the bleeding risk of blood venomous snake bites, and can be widely used in clinical practice as an important prediction method for bleeding tendency in patients bitten by blood venomous snakes.

Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

Objective:This study focused on the importance of mutual recognition of medical ethics review and the necessity of collaborative governance, combining with the current situation of mutual recognition of medical ethics review in China, and analyzing the difficulties in promoting mutual recognition of review and exploring improvement strategies.Methods:A literature research method was used to sort, summarize, refine and conclude the findings of the literature related to mutual recognition of medical ethics review.Results:Challenges persisted in the mutual recognition of medical ethics review in China, including inadequate impetus for mutual recognition among medical institutions, insufficient system and organizational support, limited acknowledgment of the audit unit's review capacity, and a lack of coordination and cooperation mechanisms.Conclusions:Implementing effective measures in benefit coordination, system and organization coordination, ability coordination, and platform coordination will facilitate the mutual recognition of medical ethics review.

Objective To construct a predictive model of thrombus clearance rate to guide the selection of therapeutic strategies for acute lower extremity venous thromboembolism patients by studying the clinic data of patients who underwent AngioJet mechanical thromboaspiration surgery.Methods By calculating the thrombus clearance rate in 83 VTE patients treated with AngioJet surgery,correlation analysis of clinical data,combined with the characteristic factors in the LASSO regression model,multiple logistic regression analysis was applied to build a prediction model of thrombus clearance rate column line graph,and the accuracy of the prediction model was evaluated using C index,calibration curve and decision curve.Results VTE type was significantly correlated with thrombus clearance rate,and the predictors in the column line plot contained:age,sex,thrombus type,surgical history,tumor history,and smoking history.The model showed great predictive power and high accuracy with a C-index of 0.795(95％CI:0.682 3-0.905 7).Decision curve analysis showed that prediction of thrombus clearance by column line plot for AngioJet procedure was effective when the threshold probability was in the range of 0.02-0.63.Conclusion In the correlation analysis,VTE type was significantly correlated with thrombus clearance.The results of this study showed that the AngioJet thrombus aspiration procedure was able to achieve a high rate of thrombus clearance in men older than 65 years with a history of tumors,a central thrombus type,no history of surgery,and no history of smoking.

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.
NF-kappa B/metabolism* ; Hepatic Stellate Cells ; Transforming Growth Factor beta1/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; Isodon ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Lipopolysaccharides/pharmacology* ; Signal Transduction ; Colchicine/pharmacology* ; Caspases