BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury （NSSI） behaviors， which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However， research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient， limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors， and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024， who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5， patients were divided into NSSI group （n=108） and non-NSSI group （n=76）. The Barratt Impulsiveness Scale-11 （BIS-11）， the Emotion Regulation Questionnaire （ERQ）， the Adolescent Self-Harm Questionnaire， and the Positive and Negative Suicide Ideation （PANSI） were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group， the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity （Z=-4.181， P<0.05）， action impulsivity （t=4.944， P<0.05）， cognitive impulsivity （Z=-3.392， P<0.05）， and total score （t=4.763， P<0.05）， and lower scores in the cognitive reappraisal of ERQ （t=-4.094， P<0.05） and total score （Z=-2.299， P<0.05）， and higher scores in the expression inhibition of ERQ （Z=-3.019， P<0.05）. The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 （r=0.434， P<0.05）. Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group （B=0.855， P<0.05）， explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. ［Funded by Wuxi Municipal Health Commission Research Project （number， Q202320）］

Objective To prepare a multifunctional mesoporous silica-based nanocarrier system(MMSN@Gem)with gemcitabine and investigate its effect on bladder cancer cells BIU-87.Methods The multifunctional meso-porous silica-based nano drug-carrying system was prepared by a modified method.Transmission electron microsco-py,high-performance liquid chromatography,and thermal imaging were used to characterize the morphology,drug-carrying and photothermal properties of MMSN@Gem.The effect of MMSN@Gem on BIU-87 bladder cancer cells was detected by in vitro experiments.Results MMSN@Gem exhibited a well-defined spherical morphology with an average particle size of(102.48±1.03)nm with a drug loading capacity of 25.04％±0.17％,and an average zeta potential of(-24.84±0.07)mV.The photothermal conversion efficiency was 40.7％which significantly enhanced the release of Gem under near-infrared irradiation.In vitro studies showed that MMSN@Gem significantly inhibited BIU-87 cell activity,induced apoptosis of BIU-87 cells,reduced migration and invasion ability,and enhanced its uptake by BIU-87 cells.Conclusions MMSN@Gem exhibits excellent photothermal properties,enhances cellular uptake efficiency,inhibits the proliferation and migration of BIU-87 cells,and promotes apoptosis,providing a promising drug delivery system for the clinical treatment of bladder cancer.

BACKGROUND:Previous studies have shown the correlation between lumbosacral sagittal plane parameters and natural absorption of lumbar disc herniation.However,the lumbosacral sagittal plane parameters included lumbar lordosis angle,lumbosacral joint angle,sacral inclination angle and many other parameters.The effects of each parameter on the natural absorption of the herniated disc were different.In addition,there are few studies on the reabsorption of a specific segment of intervertebral disc herniation at present,and most of the measured data are obtained from digital radiography or CT,while the correlation between lumbosacral sagittal plane parameters measured from MRI and reabsorption after L5/S1 intervertebral disc herniation is rarely reported. OBJECTIVE:To study the corresponding changes of lumbar sagittal plane parameters after L5/S1 intervertebral disc herniation reabsorption and to screen out the lumbosacral sagittal plane parameters with the most significant changes during intervertebral disc reabsorption. METHODS:Totally 57 patients with lumbar disc herniation who had complete MRI image data were selected and met the diagnostic criteria for lumbar disc herniation and only received non-surgical treatment for reabsorption of L5/S1 protrusion segments.MRI measured the protrusion area of the maximum protrusion plane in the coronal plane,lumbosacral sagittal plane parameters[lumbar curvature index,lumbar lordosis(α),L5/S1 disc angle(β),intervertebral height measurement,lumbosacral joint angle,sacral platform angle,sacral inclination angle,and lower lumbar lordosis angle].Besides,lumbosacral sagittal plane parameters were ranked in the importance of variables by random forest model in R software,and then significant variables were fitted with multiple linear regression.The changes between parameters before and after treatment were analyzed and compared by paired sample t-test. RESULTS AND CONCLUSION:(1)A total of 57 patients with L5/S1 lumbar disc herniation were included in this study,and the symptoms and imaging features of the patients were significantly relieved to a large extent.(2)Before treatment,there were 4 cases of grade 1,29 cases of grade 2 and 24 cases of grade 3 according to the Classification of Michigan State University.After treatment,there were 48 cases of grade 1 and 9 cases of grade 2.(3)The random forest model suggested that intervertebral height,lumbar curve index,sacral inclination angle,and lower lumbar lordosis angle changed significantly in L5/S1 disc herniation reabsorption,and the order of their change significance was lumbar curve index>intervertebral space height>sacral inclination angle>lower lumbar lordosis angle.(4)Lumbar curve index,lumbar lordosis and sacral platform angle increased,with statistical significance(P<0.05).There were no significant differences in disc angle,intervertebral height,lower lumbar lordosis angle,sacral inclination angle or lumbosacral joint angle(P>0.05).(5)Lumbar curvature index was the most significant parameter of the lumbosacral sagittal plane in herniated disc reabsorption.In addition,lumbar curve index,sacral inclination angle,and lower lumbar lordosis angle are commonly used clinically to describe the change of lumbar curvature,suggesting that L5/S1 disc herniation reabsorption is correlated with the change of lumbar curvature.It is indicated that in the treatment of lumbar disc herniation,a clinical cure can be achieved by improving or restoring the disordered lumbar curvature.

Objective To explore the process and main behavior characteristics of behavioral characteristics of patients with recurrent hypoglycemia in the degeneracy of blood glucose management.Methods A mixed-method convergent design was used to collect data.From June 2022 to April 2023,382 patients with recurrent hypoglycemia were admitted to the endocrine department of a tertiary hospital in Jiangsu were recruited to score of ego depletion.K-means clustering was conducted to analyze the distribution characteristics of patients'characteristics in blood glucose management.At the same time,19 patients who were selected from the participants of the quantitative study were recruited to attend semi-structured interviews.Results Quantitative results analysis:the average score of blood glucose management loss was(49.20±6.58),and the average scores of cognitive control,behavioral control and emotional control were(17.90±4.12),(15.49±3.64)and(15.81±3.58),respectively.The results of cluster analysis showed that behavioral characteristics could be divided into 3 groups:a cognitive depletion group,an emotional depletion group and a self-control group.Qualitative data analysis:the process of deterioration of management in patients included 3 major themes,including the antecedents of ego depletion,the process of ego depletion and the aftereffects of ego depletion.Analysis of the mixed results showed that the status of ego depletion is serious;patients ignore the behavioral elements of active participation in blood glucose management,show many irrational decision-making behaviors,and the degradation behavior characteristics of patients'blood glucose management are different.Conclusion The degeneration behavior of blood glucose management was serious and affected by single or multiple factors,continuously consuming self-control energy and causing ego depletion.To promote the long-term maintenance of blood glucose management,priority should be given to take actions to enhance patients'perceptions,emotion and behaviors,help them learn about the possible blood glucose changes,improve their understanding and recognition of the value of scientific management.

Objective Given the extensive application of machine learning(ML)in medical models and its remarkable learning and generalization capabilities,this study employed automated ML(AutoML)combined with patient demographics and clinical conditions to early assess the risk of failure in bowel preparation prior to colonoscopy.Methods A retrospective analysis was conducted on patients who underwent colonoscopy examinations in Hospital 1 and Hospital 2 from January 2022 to January 2023,and their general and clinical information was collected.According to the Boston bowel preparation scale(BBPS),a BBPS of≤5 was defined as a failure in bowel preparation,>5 was deemed satisfactory.From the data of the two hospitals,we randomly divided the dataset into a training set(n=303)and a validation set(n=76)at an 8∶2 ratio.Least absolute shrinkage and selection operator(LASSO)logistic regression(LR)model was used for feature selection,a nomogram scoring system was constructed,and models were established using AutoML based on five algorithms.Model performance was evaluated through receiver operator characteristic curve(ROC curve),calibration curves,LR-based decision curve analysis(DCA),SHAP plots,and force plots.Results Among the 379 patients,105 cases(27.7%)experienced bowel preparation failure(BBPS≤5).21 study variables were narrowed down to 10 through LASSO with 5-fold cross-validation,resulting in the development of a Nomogram chart with demonstrated reliability via calibration curves.Using the H2O platform and five algorithms[gradient boosting machine(GBM),deep learning(DL),generalized linear model(GLM),Stacked Ensemble and distributed random forest(DRF)],67 models were developed.Stacked Ensemble outperformed the others with an area under the curve(AUC)of 0.871,LogLoss of 0.403,and RMSE of 0.354,surpassing traditional LR model and other models.Variable importance contribution plots indicated significant predictive influences from factors such as the interval between laxative ingestion and examination,history of constipation,completion of laxative regimen,age,and presence of a companion during the procedure.Finally,SHAP plots and force plots revealed variable distribution patterns in binary classification predictions and the impact of variables on predictive outcomes.Conclusion The AutoML model based on the Stacked Ensemble algorithm exhibits clear clinical utility in early prediction of bowel preparation failure risk.Moreover,a clinically applicable column chart scoring tool is constructed.

Objective Rapid health technology assessment(HTA)was used to evaluate the efficacy,safety and economy of argatroban in the treatment of acute ischemic stroke,so as to provide evidence-based reference for clinical treatment decision making.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP,SinoMed databases and HTA website were electronically searched to collect the HTA report,systematic review/Meta-analysis and pharmacoeconomic research of argatroban in the treatment of acute ischemic cerebral infarction from inception to February 6,2024.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,and descriptively analyzed and summarised the results.Results A total of 21 articles were included,including 15 systematic reviews/Meta-analysis and 6 pharmacoeconomic studies.The analysis results of effectiveness showed that argatroban could improve the clinical effective rate,neurological deficit score compared with placebo,routine treatment,or other drugs(such as alteplase),but a few studies were inconsistent with the current results.The analysis results of safety showed that argatroban alone or in combination with other drugs did not increase the risk of systemic hemorrhage,intracranial hemorrhage,mortality and other adverse reactions compared with the control group,and had a favorable safety profile.The analysis results of pharmacoeconomic studies that argatroban combined with routine treatment or argatroban combined with urokinase had economic advantages.Conclusion Argatroban is generally effective and safe in the treatment of acute ischemic stroke,and it has economic advantages for patients to choose argatroban combined with routine treatment or urokinase treatment.

BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male ; Humans ; Female ; Coronary Artery Disease/genetics* ; Biological Specimen Banks ; East Asian People ; Risk Assessment/methods* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Genome-Wide Association Study

Lamin B1 (LMNB1) is highly expressed in liver cancer tissues, and its influence and mechanism on the proliferation of hepatocellular carcinoma cells were explored by knocking down the expression of the protein. In liver cancer cells, siRNAs were used to knock down LMNB1. Knockdown effects were detected by Western blotting. Changes in telomerase activity were detected by telomeric repeat amplification protocol assay (TRAP) experiments. Telomere length changes were detected by quantitative real-time polymerase chain reaction (qPCR). CCK8, cloning formation, transwell and wound healing were performed to detect changes in its growth, invasion and migration capabilities. The lentiviral system was used to construct HepG2 cells that steadily knocked down LMNB1. Then the changes of telomere length and telomerase activity were detected, and the cell aging status was detected by SA-β-gal senescence staining. The effects of tumorigenesis were detected by nude mouse subcutaneous tumorigenesis experiments, subsequent histification staining of tumors, SA-β-gal senescence staining, fluorescence in situ hybridization (FISH) for telomere analysis and other experiments. Finally, the method of biogenesis analysis was used to find the expression of LMNB1 in clinical liver cancer tissues, and its relationship with clinical stages and patient survival. Knockdown of LMNB1 in HepG2 and Hep3B cells significantly reduced telomerase activity, cell proliferation, migration and invasion abilities. Experiments in cells and tumor formation in nude mice had demonstrated that stable knockdown of LMNB1 reduced telomerase activity, shortened telomere length, senesced cells, reduced cell tumorigenicity and KI-67 expression. Bioinformatics analysis showed that LMNB1 was highly expressed in liver cancer tissues and correlated with tumor stage and patient survival. In conclusion, LMNB1 is overexpressed in liver cancer cells, and it is expected to become an indicator for evaluating the clinical prognosis of liver cancer patients and a target for precise treatment.
Animals ; Mice ; Telomerase/metabolism* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Telomere Shortening ; In Situ Hybridization, Fluorescence ; Mice, Nude ; Telomere/pathology* ; Carcinogenesis

BACKGROUND: Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults. METHODS: We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality. RESULTS: Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 - 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 - 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 - 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 - 1.37) with every additional disease. CONCLUSION Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.
Aged ; Arthritis, Rheumatoid ; Asians ; China/epidemiology* ; Humans ; Hypertension ; Middle Aged ; Multimorbidity

Objective:To investigate the expression of forkhead box protein O3(FOXO3) in pancreatic cancer and its effect on the motility and proliferation of pancreatic cancer cells.Methods:The FOXO3 expression in pancreatic cancer and adjacent tissues was retrieved from LinkedOmics database. Western blotting and real-time quantitative polymerase chain reaction were used to detect FOXO3 expression in pancreatic cancer cells and human pancreatic stellate cells. PANC-1 and MIAPaCa-2 pancreatic cancer cells with low FOXO3 expression were selected to transfect FOXO3 overexpression plasmid and negative control plasmid, respectively. The motility and proliferation ability of pancreatic cancer cells were detected by colony formation assay, cell scratch assay, Transwell assay and flow cytometry.Results:In the LinkedOmics database, the relative expression of FOXO3 protein in the cancer tissues of 64 patients with pancreatic cancer was significantly lower than that in the adjacent tissues ( t=8.36, P<0.001). The number of clones in PANC-1 cell line was (30.0±6.6) after overexpressed FOXO3, which was lower than that in negative control cells (92.7±6.7), and the difference was statistically significant ( t=11.54, P<0.001). After overexpressed FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the scratch repair rate was significantly decreased compared with the control group. In Transwell experiment, the number of cells in FOXO3 overexpressed group in PANC-1 cell lines was (21.0±6.6), which was lower than that of negative control groups (55.7±8.5), and the difference was statistically significant ( t=5.59, P=0.005). The results of MIAPaCa-2 cell line were consistent with that of PANC-1 cell line. After overexpressing of FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the proportion of cells in the G0/G1 phase decreased, while the proportion in the S phase increased. Conclusion:The expression of FOXO3 was decreased in pancreatic cancer. Overexpression of FOXO3 could significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells and induce cell cycle arrest, which is a potential target for the treatment of pancreatic cancer.