BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.

Objective:To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.Methods:We identified strong,independent single nucleotide polymorphisms(SNPs)of insomnia from the most up to date genome wide association studies(GWAS)within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus.After excluding SNPs that were significantly associated with smoking,physical activity,alcohol consumption,educational attainment,obesity,or type 2 diabetes mellitus,we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting(IVW)method.Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association.We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables.We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from ze-ro.In addition,the leave-one-out method was used for sensitivity analysis to verify the stability and relia-bility of the results.Results:We selected 248 SNPs independently associated with insomnia at the genome-wide level(P＜5 ×10-8)as a preliminary candidate set of instrumental variables.After clum-ping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs,a total of 167 SNPs associated with insomnia were included as final instrumental variables.The F statistic of this study was 39.74,which was in line with the relevance assumption of Mendelian randomi-zation.IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1.14 times more likely to develop type 2 diabetes mellitus than those without insomnia(95％CI:1.09-1.21,P＜0.001).The weighted median estimator(WME)method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus.And MR-Egger re-gression also showed that the effect was less likely to be triggered by pleiotropy.Sensitivity analyses pro-duced directionally similar estimates.Conclusion:Insomnia is a risk factor of type 2 diabetes mellitus,which has positively effects on type 2 diabetes mellitus.Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

【Objective】 To explore the risk factors of severe postoperative hemorrhage in patients with staghorn renal calculi treated with mini-percutaneous nephrolithotomy (M-PCNL), and to construct a Bayesian network model to predict postoperative hemorrhage. 【Methods】 A retrospective analysis was conducted on 160 patients with staghorn renal calculi who were treated with M-PCNL by surgeons with equivalent qualifications at the First Affiliated Hospital of Xinxiang Medical College during Jan. 2020 and Jan. 2022.A computer-generated random number method was used to divide them into a modeling group (120 cases) and a validation group (40 cases).Patients in the modeling group were divided into severe bleeding group (38 cases) and non-severe bleeding group (82 cases).The general information of the two groups was compared, and the independent risk factors of severe postoperative hemorrhage were analyzed.A Bayesian network model was constructed using R software, the inference prediction was conducted using Netica software, and the performance of the model was evaluated with receiver operating characteristic (ROC) curve. 【Results】 Multivariate logistic regression analysis showed that renal insufficiency (OR: 2.845, 95%CI: 1.563-6.515), mixmum diameter of stones ≥2 cm (OR: 2.063, 95%CI: 1.824-4.555), operation time ≥90 minutes (OR: 3.632, 95%CI: 2.365-7.11), one-stage operation (OR: 2.321, 95%CI: 1.874-6.332), and multi-channel stone removal (OR: 1.842, 95%CI: 1.366-3.687) were independent risk factors of postoperative severe hemorrhage (P<0.05).Based on the above parameters, a Bayesian network model was established, which was then evaluated with the modeling and validation groups internally and externally.The AUC of the modeling group was 0.879 (95%CI: 0.804-0.931, P<0.001), with sensitivity and specificity being 87.68% and 89.63%, respectively.The AUC of the validation group was 0.875(95%CI: 0.818-0.908, P<0.001), with sensitivity and specificity being 87.55% and 89.40%, respectively.The model showed good discrimination. 【Conclusion】 Renal dysfunction, mixmum diameter of stones ≥2 cm, operation time ≥90 minutes, one-stage operation, and multi-channel stone removal are risk factors of severe hemorrhage in patients after M-PCNL.The prediction model has good predictive ability and can effectively describe the complex mechanism between diseases and risk factors.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Objective:To analyze and evaluate the equity of children's health in countries along the"the Belt and Road",promote further attention to children's health in countries along the route,and promote cooperation and exchanges on children's health between China and countries along the"the Belt and Road".Methods:Using concentration index and concentration curve to measure overall equity,and using the Thiel index for intraregional and interregional euqity measurement.Results:The under-five mortality concentration index is 0.349 7,the concentration curve is below the absolute fair line.The Thiel index shows that inequality in low-income countries,lower-middle-income countries,upper-middle-income countries and high-income countries is the leading cause of child health inequities in the"the Belt and Road"countries.Conclusion:There is inequity in the health of children in countries along"the Belt and Road Initiative",countries along the"the Belt and Road"should take comprehensive measures to reduce the under-five mortality rate,at the same time strengthen international cooperation to further promote equity in children's health in"Belt and Road"countries.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D² (R²= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

ObjectiveTo adapt the Stanford Expectations of Treatment Scale（SETS） into Chinese（C-SETS） and test the feasibility， validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome（IBS-D） with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine（TCM）. MethodsWe obtained authorisation from the developer of the SETS， and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment； the feasibility was assessed by the recall rate， completion rate and the duration of filling out the scale； the reliability was assessed by Cronbach's α； the structural validity was assessed by exploratory and confirmatory factor analysis， and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items， with the 1st， 3rd， and 5th rating items constituting the Positive Expectations subscale， and the 2nd， 4th， and 6th rating items constituting the Negative Expectations subscale， each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%（96/96）， the completion rate was 89.58%（86/96）； Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854， respectively； exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4， and that the six entries could be used by both factors to explain 77.092% of the total variance； validation factor analysis showed that the goodness-of-fit index， comparative fit index， root mean square of approximation error， canonical fit coefficient， and chi-square degrees of freedom ratio took the values of 0.943， 1.003， 0， 0.943， and 0.626， respectively； and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility， reliability， and validity， which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.

Objective·To construct a probiotic(Escherichia coli Nissle1917,EcN)system(EcN@PVA-ALG)loaded on polyvinyl alcohol(PVA)/alginate(ALG)hydrogel(PVA-ALG)rich in negative hydroxyl groups,and to explore its colonization in the inflammatory site of colon and its therapeutic effect on dextran sulfate sodium salt(DSS)-induced inflammatory bowel disease(IBD).Methods·EcN suspension was added to the PVA-ALG hydrogel,and then EcN@PVA-ALG hydrogel probiotic complex was obtained after screening and centrifugation.The synthesis of PVA-ALG hydrogel was verified by rheometer.The surface charge of EcN@PVA-ALG was detected by potentiometer and the load of EcN on PVA-ALG was observed by fluorescence microscope.The absorbance of EcN@PVA-ALG at 600 nm was detected by enzyme labeling instrument.Meanwhile,the bacterial plate count of EcN@PVA-ALG complex suspension was taken to study the growth activity of EcN in EcN@PVA-ALG.The CCK-8 kit was used to assess the inhibitory ability of EcN@PVA-ALG on HEK cell proliferation.In vivo imaging system(IVIS)was used to firstly analyze the enrichment of PVA-ALG on inflammatory colon to study its inflammatory targeting property;then EcN was loaded on PVA-ALG,and IVIS was used to observe the enrichment of EcN@PVA-ALG on inflammatory colon to study its ability to colonize the inflammatory site.To establish the model of IBD mice induced by DSS,EcN@PVA-ALG group(n=5)was given 1×108CFU EcN@PVA-ALG every day for 5 d,and PVA-ALG group,EcN group,PBS group and healthy control group with 5 mice were set up.During the treatment,the body mass of the mice was recorded every day.After treatment,the colonic tissue was taken,and the length of colon was measured.The disease activity index(DAI)score was graded.The levels of inflammatory cytokines,including tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-10 and transforming growth factor-β(TGF-β)were detected,and the pathological evaluation of colonic tissue was made by H-E staining.Results·Both PVA-ALG and EcN@PVA-ALG were negatively charged.EcN was successfully loaded onto PVA-ALG and PVA-ALG did not affect the growth viability of EcN,which contributed to the subsequent colonization of inflammatory colons.PVA-ALG had a favorable safety profile on normal cells.Compared with healthy controls,PVA-ALG had more than 2-fold enrichment effect on inflammatory colon tissue.In vitro and in vivo experiments revealed that EcN@PVA-ALG complex loaded with EcN had 8 times higher enrichment effect on inflammatory tissue than EcN without any modification.After EcN@PVA-ALG treatment,the body weight of mice recovered rapidly.The increase of DAI was significantly inhibited.The length of colon was similar to that of healthy mice.The levels of TNF-α and IL-6 decreased,while the levels of IL-10 and TGF-β increased.The crypt structure of colon tissue recovered.Conclusion·Compared to unmodified EcN,EcN@PVA-ALG promotes the colonization of EcN at inflammatory sites of colon and allows it to exert better efficacy on treating DSS-induced IBD.