Objective To construct and validate a risk prediction model for delayed healing of venous leg ulcer(VLU),so as to provide a reference basis for early identification of people at high risk of delayed healing.Methods Using a convenience sampling method,331 VLU patients attending vascular surgery departments in 2 tertiary A hospitals in Sichuan Province from January 2018 to December 2022 were selected as a modeling group and an internal validation group,and 112 patients admitted to another tertiary A hospital were selected as an external validation group.Risk factors for delayed healing in VLU patients were screened using univariate analysis,LASSO regression,and multivariate logistic regression analysis,and a risk prediction model was constructed using R software,and the predictive effects of the models were examined using the area under the receiver operating characteristic curve,the Hosmer-Lemeshow test,decision curve,and the bootstrap resampling for internal validation and spatial external validation were performed,respectively.Results The predictors that ultimately entered the prediction model were diabetes(OR=4.752),deep vein thrombosis(OR=4.104),lipodermatosclerosis(OR=5.405),ulcer recurrence(OR=3.239),and ankle mobility(OR=5.520).The model had good discrimination(AUC:0.819 for internal validation and 0.858 for external validation),calibration(Hosmer-Lemeshow test:χ2=13.517,P=0.095 for internal validation and χ2=3.375,P=0.909 for external validation)and clinical validity.Conclusion The model constructed in this study has good differentiation and calibration,and it can effectively predict people at high risk of delayed healing of VLU,which facilitates targeted clinical interventions to improve ulcer outcomes and reduce the risk of delayed ulcer healing.

Objective To explore the related risk factors of hypokalemia in elderly patients with acute cerebral hemorrhage(ACH),and construct a risk prediction model based on logistic regres-sion.Methods A total of 190 elderly ACH patients treated in Foshan Hospital of Traditional Chi-nese Medicine from June 2022 to May 2024 were enrolled as study objects,and were divided into hypokalemic group(potassium＜3.5 mmol/L,n=51)and normal group(potassium 3.5-5.5 mmol/L,n=139)according to whether hypokalemia occurred.Logistic regression model was used to analyze the risk factors of hypokalemia in the elderly ACH patients.Based on the identified risk factors,a comprehensive index model was constructed.ROC curve was drawn to analyze the diag-nostic value of the index for occurrence of hypokalemia in the patients.Results Larger female ra-tio,higher NIHSS score at admission,elevated urea nitrogen and blood creatinine at admission,and higher glomerular filtration rate(GFR)≤60 ml/min,and ratio of using hydrochlorothiazide＞20 mg/d were observed in the hypokalemic group than the normal group(P＜0.01).Univariate logistic regression analysis showed that female,NIHSS score at admission,urea nitrogen at ad-mission,serum creatinine at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d were risk factors for hypokalemia in the ACH patients(P＜0.05,P＜0.01).Multivariate lo-gistic regression analysis indicated that female,NIHSS score at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d were independent risk factors for hypokalemia in the elderly ACH patients(OR=6.393,95％CI:2.138-19.112,P=0.001;OR=3.123,95％CI:2.161-4.513,P=0.000;OR=3.327,95％CI:1.137-9.736,P=0.028;OR=3.111,95％CI:1.083-8.933,P=0.035).ROC curve analysis revealed that the AUC values of female,NIHSS score at admission,GFR,hydrochlorothiazide dose and comprehensive index in predicting hypokalemia in elderly ACH patients were 0.621,0.897,0.601,0.613 and 0.857,with a sensitivity of 52.90％,76.50％,49.00％,54.90％and 72.50％,and a specificity of 71.20％,88.50％,71.20％,67.60％and 87.80％,respectively.Conclusion Female,NIHSS score at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d may affect the occurrence of hypokalemia in elderly ACH pa-tients,and our comprehensive index model based on these risk factors has high performance in predicting the occurrence of hypokalemia in elderly ACH patients.

【Objective:】 To deeply understand the current situation and hotspots of drug clinical trials risk management in China. 【Methods:】 Co-word analysis and social network analysis were used to sort out the study results of risk management in drug clinical trials in China. 【Results:】 The trend of risk research of drug clinical trials in China was generally on the rise. The research hotspots focused on four areas: drug supervision and pharmacovigilance, risk management of drug clinical trial institutions, ethical review of drug clinical trials, and risk management of drug clinical trials. 【Conclusion:】 In the future, China should gradually improve the risk management system and supervision system of drug clinical trials, explore to establish a risk-based quality management and ethical review system of drug clinical trials, and enhance the risk assessment and coping ability of institutions.

【Objective:】 To sort out the influencing factors of drug clinical trial risks and improve the risk management level of drug clinical trials in China. 【Methods:】 The literature analysis method was used to sort out the literature related to the risk management of drug clinical trials in China, and the text analysis method was used to summarize and refine the influencing factors of drug clinical trial risks. 【Results:】 The risk categories of drug clinical trials were divided into 5 parts, namely drug clinical trial institution management, ethics committee management, clinical trial designs, researchers, and subjects, involving 13 main risk influencing factors and 21 specific risk points. 【Conclusion:】 By strengthening the construction of drug clinical trial institutions and ethical management capabilities, optimizing research protocol design, enhancing researchers’ awareness and ability, and establishing a subject management system to improve the quality of drug clinical trials.

Risk assessment of clinical trials is of great significance to improve the quality of clinical trials. Through systematic comparative analysis of risk assessment tools for clinical trials in Britain, Germany and France, this paper found that the three countries’ risk assessment tools were consistent in terms of legal system guarantee and assessment process, but there were obvious differences in the basic risk classification and risk grading standards of clinical trials. Based on the experience of Britain, France and Germany, this paper proposed to improve the relevant regulations and documents of clinical trial risk management in China from the perspective of Chinese national conditions, further explore the factors affecting clinical trial risk, and develop and design clinical trial risk assessment tools with different discipline characteristics according to the specialties of the discipline to improve the quality and level of clinical trials.

Objective:To analyze the intervention effect of rehabilitation platform-based online psycho-education on patients with bipolar disorder (BD) in remission stage.Methods:In this randomized controlled study, 91 patients with BD in remission stage who attended the community health center in Xicheng District, Beijing from July to August 2021 were randomly divided into a test group (46 cases) and a control group (45 cases) according to a 1∶1 ratio using the random number table. Baseline data were collected from both groups, and the control group received conventional medication and community telephone follow-up, while the test group was given online mental health education in the form of a WeChat subscription number on this basis, including BD mental health education course push (twice a week) and disease self-management (daily recording of mood, sleep, medication, exercise and gratitude diary), and the intervention period was 6 months in both groups. During the intervention, one patient in the test group was admitted to hospital due to exacerbation of mental illness and the trial was terminated. A total of 90 cases were included in the study. The scores of Medication Adherence Rating Scale (MARS), Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS) and Perceived Devaluation-Discrimination Scale (PDD) were assessed at baseline, after 3 months and 6 months of intervention in both groups, respectively. And the differences in baseline data between the two groups were compared using two independent samples t test and χ2 test, and the repeated-measures ANOVA was used to compare the differences in MARS, HAMD, YMRS, and PDD scores between the two groups before and after the intervention, and to analyze the intervention effects of network mental health education based on the rehabilitation platform on patients in remission stage of BD. Results:After 6 months of intervention, MARS scores in the test group was significantly higher than that in the control group [(8.47±1.75) vs (7.47±1.85)], and was significantly higher than that at baseline (7.36±2.13) and after 3 months of intervention (8.04±1.68) (all P<0.05). YMRS and PDD scores in the test group were significantly lower than those at baseline after 3 and 6 months of intervention [YMRS, 2.0(1.0,4.0),2.0(0,3.0) vs 3.0(1.0,5.5); PDD, (31.18±4.65), (30.13±4.76) vs (32.51±4.51)] (all P<0.05); the differences in YMRS and PDD scores in the control group were not statistically significant (all P>0.05). There was no statistically significant difference in HAMD scores between the two groups before and after the intervention (all P>0.05). Conclusion:Combining mental health education based on rehabilitation platform with conventional medication and community management can significantly improve the medication compliance of patients with BD in remission stage, and improve their manic symptoms and reduce the stigma of the disease.

The peripherally inserted central catheter (PICC) in neonates has solved the long-term venous access needs of hospitalized infants in the Neonatal Intensive Care Unit (NICU) . The application of technology is accompanied by the risk of complications. Providing safe and high-quality vascular access for neonates through standardized operations is of great significance. The National Association of Neonatal Nurses (NANN) has formulated the Practice Guideline for PICC in Neonates and revised it into the the Practice Guideline for Peripherally Inserted Central Catheter in Neonates (Third Edition) in 2015, aiming to support the bedside nursing practice of neonatal PICC, reduce the occurrence of complications, and promote neonatal safety. This article interprets the recommended points for early identification, management, and prevention of complications after neonatal PICC catheterization in the guidelines.

Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.

BACKGROUND: Inhibiting the degradation of extracellular matrix in the intervertebral disc can delay the degenerative process of intervertebral disc. Matrix metalloproteinases-3 (MMP3) is considered as a key enzyme for degradation of extracelular matrix components such as type II collagen and aggrecan.
OBJECTIVE:To construct the short hairpin RNA lentiviral vector targeting human MMP3 gene and to detect its efficiency of gene silence by infecting human degenerative nucleus pulposus cells.
METHODS:According to the human MMP3 mRNA (NM_002422.4) sequence, four groups of the short hairpin RNA gene sequences targeting MMP3 were designed, synthesized and annealed to form double stranded DNA fragments, which were connected with the LV3 vectors digested by BamHI andEcoRI enzymes, and then transfected into the competent cels. The positive clones were identified by PCR, and analyzed by sequencing. The packaging and titer of lentivirus were determined after transfecting 293T cells. Human degenerative nucleus pulposus cels were infected with lentivirus vector, and the transfection efficiency of each group was observed under inverted fluorescence microscope. The interfering efficiency was detected by real time-PCR and western blot at 72 and 96 hours.
RESULTS AND CONCLUSION:The ds-oligo DNA was successfully inserted into the lentiviral vector as confirmed by electrophoresis and sequence analysis. The recombinant lentivirus was harvested from 293T cels with a viral titer of 1-5 ×108 TU/mL. RNA interference targeting the GCC AGG CTT TCC CAA GCA AAT sequences with the highest interfering efficiency in MMP3 gene at 72 and 96 hours resulted in suppression of MMP3 mRNA expression by 98% and 72%, respectively; and at 96 hours, the interfering efficiency of protein expression was 57.2%. The recombinant lentivirus vector containing RNA interference targeting MMP3 gene is successfuly constructed, which lays a foundation for further studies on the MMP3 function and gene therapy.