Objective: To explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization (MR) analysis，and to investigate the potential mediating role of plasma metabolites. Methods: Data on gut microbiota，plasma metabolites，and upper urinary tract stones were obtained from publicly available Genome-wide Association Studies (GWAS).Bidirectional MR analysis was performed to examine the causal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contribute to upper urinary tract stones through plasma metabolites，and the mediating effects and mediator ratio were calculated.The inverse variance weighted (IVW) method was used as the primary analytical tool，supplemented by Bayesian weighted Mendelian randomization (BWMR)，MR-Egger，and weighted median (WM) analyses.Horizontal pleiotropy and heterogeneity tests were conducted to ensure the robustness of the findings. Results: Bidirectional MR analysis identified causal associations between 7 gut microbial taxa and 6 microbial metabolic pathways with upper urinary tract stones，while the development of upper urinary tract stones affected 13 gut microbial taxa and 5 metabolic pathways.Additionally，43 plasma metabolites (including 27 identified metabolites，8 unidentified metabolites，and 8 metabolite ratios) were causally associated with upper urinary tract stones.The two-step MR analysis identified 11 potential causal pathways.After metabolic pathways and unidentified metabolites were excluded，a causal link mediated by Bacteroides faecis between galactarate and upper urinary tract stones was confirmed，with a mediation proportion of 16.99% (95%CI：5.76%-33.95%，P=0.0371). Conclusion: This study establishes a causal relationship between parabacteroides and upper urinary tract stones，and elucidates the mediating role of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

Objective:To evaluate the teaching effect of Emergency Nursing practice course using scenario simulation teaching combined with formative assessment. Methods:The subjects were selected from vocational nursing students of Batch 2015 (control group, n=49) and Batch 2016 (intervention group, n=40). The control group adopted the scenario simulation teaching method, and the intervention group added formative assessment on the basis of simulation teaching. The end-of-term theoretical scores of Emergency Nursing and the scores of students' general self-efficacy scale were used as evaluation tools. SPSS 22.0 statistical software was used for data processing and analysis. Results:The scores of the intervention group (85.20±8.05) were higher than those of the control group (79.73±8.46), with statistical significance ( P<0.05). The scores of self-efficacy in both groups were improved, while the scores of the control group after the course (2.68±0.42) were higher than those before the course (2.61±0.47), but there was no statistical significance. The scores of the intervention group after the course (2.78±0.43) were higher than those before the course (2.62±0.43), with statistical significance. Conclusion:The application of scenario simulation teaching combined with formative assessment in the practical course of Emergency Nursing can be helpful to improve students' self-efficacy and comprehensive ability of first aid.

Objective To evaluate the role of α2A adrenergic receptor (α2AAR) in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation (H/R)caused injury to alveolar type Ⅱ epithelial cells.Methods Type Ⅱ] alveolar epithelial cells of rats RLE6TN cells cultured in vitro were divided into 4 groups (n =6 each) using a random number table method:control group (group C),H/R injury group (group H/R),dexmedetomidine group (group D) and α2A AR small interfering RNA (siRNA) plus dexmedetomidine group (group α2AAR-siRNA+D).H/R was produced by exposing cells to 1％ O2-5％ CO2-94％ N2 for 24 h followed by 4-h reoxygenation.Cells were incubated for 1 h with dexmedetomidine at the final concentration of 1 nmol/L,and then H/R model was established in group D.In group α2AAR-siRNA+D,cells were transfected with 50 nmol/L α2AAR-siRNA,48 h later dexmedetomidine at the final concentration of 1 nmol/L was added,cells were incubated for 1 h,and then H/R model was established.The cell viability was measured using CCK-8 method,cell apoptosis rate was determined by flow cytometry,and the expression of TLR4 and NF-κB was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group H/R (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group H/R,the cell viability was significantly increased,the apoptosis rate was decreased,and the expression of TLR4 and NF-κB was down-regulated in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group α2AAR-siRNA+D (P＞0.05).Compared with group D,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group α2AAR-siRNA+D (P＜0.05).Conclusion The mechanism by which dexmedetomidine inhibits TLR4/NF-κB signaling pathway activation may be related to activating α2AAR during H/R-caused injury to alveolar type Ⅱ epithelial cells.

Objective To evaluate the risk factors of delirium in patients of intensive care unit ( ICU) by different scale systems.Methods Totals of 440 patients were enrolled in this investigation.Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Intensive Care Delirium Screening Checklist ( ICDSC) were used when patients in-and out-ICU.Other risk factors and APACHE Ⅱ score were recorded. Multiple linear regression was done between each scale and all risk factors.Results The scores of APACHEⅡ, SAS,SDS and ICDSC were (9.8 ±3.2), (43.8 ±11.3), (43.1 ±10.8) and (2.43 ±2.00) when patients discharged from ICU.Those values were (17.3 ±5.5), (48.3 ±12.7), (48.5 ±12.3) and (1.36 ±0.81) when patients first admitted to ICU.There were significant differences ( t =7.549,3.004,3.780,-3.329, respectively;P<0.05).Multiple linear regression analysis showed that the score of SAS was correlated with duration in ICU, APACHEⅡscore and drainage catheter amount (R2 =0.515,F=14.139,P<0.001).The score of SDS was correlated with duration in ICU and drainage catheter amount ( R2 =0.444,F=16.395,P<0.001) .The score of ICDSC was correlated with education, duration in ICU, duration of mechanical ventilation and APACHEⅡscore (R2 =0.803,F=39.769,P<0.001).Conclusions The sensitivity of ICDSC is high and can be used to screen delirium in ICU.The incidence of delirium increases with the duration of ICU stays.

Objective To explore the influence of genetic and environmental factors on emotional and behavioral problems in children and adolescents using twins quantitative method. Methods One hundred fifty-six twins pairs, aged from 6 to 18, were included in the present study. The parental version of the strengths and difficulties questionnaire (SDQ)was used to evaluate their emotional and behavioral problems. The DNA test of twin zygosity was conducted using DNA extracted from buccal mucosa or venous blood samples. The influence of genetic and environmental factors on emo-tional and behavioral problems was analyzed using structural equation modeling(SEM). Results Shared environment and special environment had impact on emotional symptoms and their contribution to the total variance of emotional symp- tom was 0.42 and 0.58, respectively. Prosocial behavior was mainly affected by shared environment and the contribution of shared environment to the total variance of prosocial behavior was 0.89. Genetic factors had greater influence on hyperac-tivity/attention deficit and the contribution of genetic factors to the total variance was 0.62. Shared environment had more influence on conduct disorder and the contribution of shared environment to total variance was 0.56. Heredity, shared envi-ronment and special environment had impact on peer problems and their contribution to the total variance was 0.24, 0.33 and 0.43, respectively. Conclusion In child and adolescent period, emotional symptoms are only affected by environ-ment, while behavior problems are affected by the combination of heredity and environment. Different behavior problems are affected by different genetic and environmental factors.

Objective To evaluate the effect of percutaneous coronary intervention (PCI) or thrombolysis,in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA),in the presence of ST-elevation myocardial infarction (STEMI).We demonstrated the benefits of the two therapies on ROSC patients in hospital discharge and neurological recovery,and clarified the importance of ROSC,so as to guide the treatments for OHCA in the presence of STEMI.Methods It was performed a meta-analysis of clinical studies located in PUBMED and MEDLINE databases from January 1995 to October 2011.OHCA patients with ROSC were as our study objects,the hospital discharge and neurological recovery rates,of patients with and without PCI or thrombolysis,were assessed in patients with ROSC after OHCA in the presence of STEMI.In the same Cohort Study,between received and rejected PCI,or between received and rejected thrombolysis in OHCA patients with ROSC as treated group and control group,using Review Manager 5.1 software to analyze,respectively.Furthermore,we also compared the differences in hospital discharge and neurological recovery rates between patient groups who received PCI or thrombolysis by Pearson x2 analysis.Results The meta-analysis showed that the rate of hospital discharge improved with both PCI (odds ratio [OR],1.65 ; 95％ confidence interval [CI],1.05-2.59,P ＜ 0.01)and thrombolysis (OR,2.03 ; 95％ CI,1.24-3.34,P ＜ 0.01) in patients with ROSC after OHCA,in the presence of STEMI.We also found that there were not significant differences between with PCI and with thrombolysis in the rate of hospital discharge (63.00％ vs.65.19％,P =0.548) and neurological recovery (88.62％ vs.91.25％,P =0.351) for the patients with ROSC after OHCA (P ＞0.05).Conclusions In patients with ROSC after OHCA in the presence of STEMI,both PCI and thrombolysis improved hospital discharge rates.Furthermore,there were similar efficacy in hospital discharge and neurological recovery rates between with PCI and with thrombolysis.

Objective To investigate the therapeutic effects of enhanced external counterpulsation (EECP) on cerebral edema and cerebral blood flow perfusion with MRI following cardiac arrest (CA) and on successful return of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in dogs.Methods Sixteen beagle dogs were induced CA with alternating current on epicardium,then were randomly (random number) divided into the EECP and control group after successful ROSC.MR scanning brain of all animals was carried out by diffusion-weighted imaging (DWI) and perfusion weighted imaging (PWI) before CA and on the first,second and third days after ROSC.Blood pressure,right common carotid artery flow,and intracranial microcirculation perfusion were measured.Results There were no significant differences in mean artery pressure at all intervals between two groups (P ＞ 0.05).There was significant increase in right common carotid artery blood flow and intracranial microcirculation of dogs in EECP group compared with the control group (P ＜ 0.05).Apparent diffusion coefficients (ADC) of water molecule on the first and third days after ROSC were significantly higher in the EECP group than those in the control group (P ＜ 0.05).Ratios of post-ROSC relative cerebral blood flow (RCBF) /original cerebral blood flow were higher in the EECP group than those in the control group on the first,second and third days after ROSC (P ＜ 0.05).Conclusions EECP treatment could improve cerebral blood flow perfusion and relieve ischemic cerebral edema,alleviating brain injury in dogs following CA and successful ROSC.

Objective To explore whether the peritoneal cooling was better than other cooling methods on protection neuron damage of the hippocampus CA1 after cardiopulmonary resuscitation (CPR) in New Zealand rabbits.Methods Forty eight adult New Zealand rabbits were induced ventricular fibrillation by AC current and were resuscitated after cardiac arrest for 5 minutes.The rabbits were randomly divided into four groups according to the way of cooling methods,nomothermia group ( NT),peritoneal cooling group (PC),surface cooling group (SC) and local cooling group (LC).The changes of tympanic membrane temperature were recorded in each animal and blood plasma concentrations of electrolyte were tested in each group at different time points after restore of spontaneous circulation (ROSC).Brain tissue were removed,the numbers of vigorous and apoptotic neurons in the hippocampus CA1 area were counted after ROSC at 72h.One-way ANOVA or Mann-Whitney rank was used to determine the statistical significance between two groups.LSD-t test for multiple comparisons,R × C test for ROSC comparisons,a two-tailed value of P ＜0.05 was considered statistically significant. Results Hypothermia was rapidly induced in PC after ROSC,and the time of arriving at target temperature was (26 ±7) min in PC,(60 ±9) min in SC,(69 ± 12) min in LC respectively; in the maintain hypothermia period,the tympanic membrane temperature was maintained at 33～ 35 ℃ in each group exception nomothermia group (NT).There were no differences with main electrolyte,acid-abase liquid balance and renal function between each group at each time point after ROSC.The numbers of vigorous neurons in hippocampus CA1 area were ( 37.07 ± 6.43 ) /40 × in NT group,(35.13 ± 6.97) /40 × in LC group,(55.76 ± 10.13 ) /40 × in PC group,and (50.70 ± 7.38 ) /40 × in SC group (PC:NT,P＜0.01,SC:NT,P＜0.01,PC:SC,P=0.043,PC:LC,P＜0.01,LC:NT,P=0.52).The numbers of apoptotic neurons were (44.07 ±6.09) /40 × in NT group,(29.88 ±4.81 ) /40× in PC group,( 33.55 ± 5.67 ) /40 × in SC group and ( 42.27 ± 5.20 ) /40 × in LC group respectively (PC:NT,P ＜0.01,SC:NT,P ＜0.01,PC:LC,P ＜0.01,SC:LC,P ＜0.01,PC:SC,P=0.026,LC:NT,P =0.364 ).Conclusions The new peritoneal cooling method could rapidly induce and maintain hypothermia,and it had better protections on neurons in hippocampus CA1 than surface cooling and local cooling method after ROSC in New Zealand rabbits.

The famous Abraham Flexner's 1910 report to the Carnegie Foundation launched the modern medical educmion.The report'S focus on the medical education standards and the curricula frameworks was laudable and appropriate.At the centennial of this report.we were still able to get a lot of inspiration and the direction of development and reforms of medical education by reviewing Flexner'd Report.