【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cul-tured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca2+indicator(Cal-590 AM).The effect of Piezo 1 on apop-tosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activa-tor Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank controlgroup,apoptosis increased in the fluid shear group(P＜0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 chan-nel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P＜0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.

Objective:To construct a comprehensive and targeted risk assessment index system for central venous catheter (CVC) dysfunction in patients undergoing continuous renal replacement therapy (CRRT) .Methods:The risk assessment indicators for CVC dysfunction in CRRT patients were determined based on literature review and Delphi expert consultation. From July to September 2023, 19 experts in hemodialysis were selected for expert consultation. Based on expert opinions and screening criteria, corresponding indicators were added, deleted, or modified. After the second round of consultation, the expert opinions tended to be consistent.Results:A total of 17 experts completed two rounds of consultation. In the two rounds of consultation, the effective response rates of the questionnaires were 89.5% (17/19) and 100.0% (19/19), respectively, and the expert authority coefficients were 0.87 and 0.88, respectively. The Kendall harmony coefficients were 0.131 and 0.138 ( P<0.05). The final risk assessment index system included seven primary indicators and 44 secondary indicators. Conclusions:The risk assessment index system for CVC dysfunction in CRRT patients constructed is scientific, reliable, and practical, which can provide reference for clinical medical and nursing staff to improve catheter risk management in CRRT patients.

OBJECTIVE To study the vasorelaxant effects and mechanism of polyphenol compound 2，4′，5′-trihydroxy-5，2′- dibromo-diphenyl-methanone（LM49）on isolated aortic rings of rats. METHODS Thoracic aortic vascular rings of rats were collected. Using the diastolic rate as index ， the effects of different concentrations of LM 49 on endothelium-intact and endothelium-denuded aortic rings pre-contracted by norepinephrine （NE，1×10－6 mol/L）or KCl （60 mmol/L）were investigated. After pre-culturing vascular rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester （L-NAME，0.1 mmol/L） and cyclooxygenase inhibitor indomethacin （1×10－5 mol/L），as well as pre-culturing vascular rings by 4 potassium channel blockers [BaCl 2（0.1 mmol/L），tetraethylammonium（TEA，5 mmol/L），4-aminopyridine（4-AP，0.1 mmol/L）and glibenclamide （1×10－5 mol/L）]，the vasorelaxant effect of different concentrations of LM 49 on the vascular rings were investigated by using the same method. With the percentage of vasoconstriction as the index ，using KCl （60 mmol/L），NE（1×10－6 mol/L），calcium channel blocker verapamil （1×10－6 mol/L）and sarcoplasmic Δ 基金项目 重大新药创制国家科技重大专项 （No.2018ZX097- reticulum Ca 2 +-adenosine triphosphate （ATP） enzyme pump inhibitor thacarotene （TG，1×10－6 mol/L）to induce the release of calcium in vascular rings in the absence of calcium. CaCl was added cumulatively ，and the effect of LM 49 on the cxyw06，vasoconstriction caused by calcium influx induced by CaCl 2 was investigated. RESULTS 3×10－6，5×10－6，1×10－5 mol/L LM49 had a significant relaxation effect on NE and KCl precontracted vascular rings （P＜0.01）； whether the endothelium was removed or not had no significant effect on the vasodilation of LM 49（P＞0.05）. After L-NAME ，indomethacin， TEA and 4-AP was pre-incubated ，different concentrations of LM 49 had no significant effects on aortic rings precontracted by NE （P＞0.05）. Glibenclamide and BaCl 2 could inhibit the vasorelaxant effects of LM 49 on aortic rings precontracted by NE （P＜0.01）. In the absence of calcium ，LM49 could inhibit the contraction caused by calcium influx induced by accumulated CaCl 2 after pre-incubation with KCl ，NE，verapamil and TG （P＜0.01）. CONCLUSIONS LM49 evokes significant relaxation of isolated aortic vascular rings without endothelium dependence ；the mechanism of which is inducing ATP-sensitive potassium channel ， inward rectifier potassium channel open and restraining extracellular Ca 2 + influx via voltage-gated calcium channel ， receptor-operated calcium channel and store-operated calcium channel.

Objective: To evaluate the status and influencing factors of the mental health of patients with COVID-19 during isolation treatment. Methods: From February 2nd to 16th, 2020, 106 COVID-19 patients were anonymously investigated for their mental health status using onlinequestionnaires (including Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7, Patient Health Questionnaire-15 scales). The patients were from Tongji Hospital Affiliated to Tongji Medical College ofHuazhong University of Science and Technology. After data processing, SPSS19.0 was used for statistical analysis. Results: Of the 106 COVID-19 patients, 46 were male and 60 were female, with an age of (35.90±11.92) years. The detection rates of depression, anxiety and somatic symptoms in those patients were 49.06% (52/106) , 56.60% (60/106) and 69.81% (74/106) respectively. The severe cases of depression (scale score greater than 19) , anxiety (scale score greater than 14) and somatic symptoms (scale score greater than 14) accounted for 9.43% (10/106) , 15.09% (16/106) and 20.75% (22/106) respectively. In addition, 67.92% (72/106) of the patients had sleep problems, 24.53% (26/106) had self-mutilating or suicidal thoughts, and 28.30% (30/106) required psychological counseling—all of which were at significantly higher percentages than those of the general population. Only 39.62% (42/106) of the examined patients had neither deression nor anxiety. By using the non-parametric test of rank conversion for analysis, and the results showed that both married patients and nucleic-acid-positive patients had more severe depressions, and both married patients and anoxemicpatients had more severe somatic symptoms. Conclusion This mental health assessment showed that depression, anxiety, and various somatic symptoms exist among the COVID-19 patients, and therefore early identification and intervention should be conducted to avoid extreme events such asself-mutilating or suicidal impulsivity, with a greater focus on both married patients and patients with severe symptoms.

Objective:To evaluate the efficacy and safety of recombinant human tumor necrosis factor-α receptorⅡ: IgG Fc fusion protein (rhTNFR:Fc) in the treatment of drug-induced toxic epidermal necrolysis (TEN) .Methods:From 2009 to 2018, 22 patients with TEN were enrolled from 8 centers such as the Second Affiliated Hospital of Soochow University, including 10 males and 12 females, whose age ranged from 22 to 75 years. These patients were subcutaneously injected with rhTNFR:Fc at a dose of 25 mg once every 3 days for 6 - 8 consecutive sessions, and the initial dose was doubled. The drug eruption area and severity index (DASI) score and DASI improvement indices (DASI50, DASI75 and DASI90) were assessed before treatment and on days 4, 7, 10, 13, 16, 19, 22 and 25 after treatment; cytometric bead array (CBA) technology was used to detect the level of tumor necrosis factor (TNF) -α in peripheral blood and blister fluid samples. During the treatment, body temperature, rash changes, liver and kidney function of patients were monitored, and adverse reactions were recorded. Statistical analysis was carried out by using repeated measures analysis of variance, paired t test and Pearson correlation analysis. Results:Of the 22 patients, the temperature stopped rising in 20 patients without infections 24 - 72 hours after the first treatment, and returned to normal after 48 - 120 hours. Among the 22 patients, new blisters stopped appearing 24 - 48 hours after the first treatment, the skin color changed from bright red to dark purple after 48 - 96 hours, and most skin lesions subsided after 2 weeks. After 2 - 4 weeks of treatment, levels of alanine aminotransferase and aspartate aminotransferase returned to normal in 19 patients with abnormal liver function. After 4 - 13 days of treatment, levels of creatinine and urea nitrogen stopped rising in 7 patients with abnormal renal function. During the treatment, the DASI score of the 22 patients gradually decreased ( F = 532.81, P < 0.01) , from 53.64 ± 8.67 before treatment to 2.05 ± 1.21 on day 25 after treatment ( t = 26.60, P < 0.001) . On day 10 after treatment, 22 patients (100%) achieved DASI50; on day 19, 22 (100%) achieved DASI75; on day 25, 20 (90.90%) achieved DASI90. The level of TNF-α in peripheral blood of the 22 patients gradually decreased along with the extension of treatment duration, from 33.95 ± 27.90 ng/L before treatment to 2.38 ± 0.79 ng/L on day 25. Before treatment, the level of TNF-α in blister fluid of 15 patients was 111.99 ± 99.41 ng/L, and the ratio of blister-fluid TNF-α level to peripheral blood TNF-α level was 1.83 - 28.21. Before treatment, no correlation was observed between the serum level of TNF-α and DASI score in the 22 patients ( P = 0.10) , while the blister-fluid TNF-α level was positively correlated with DASI score in the 15 patients ( r = 0.59, P = 0.02) . No acute adverse reactions were observed during the treatment. All the 22 patients completed the treatment and were discharged with complete recovery. During 6 months of follow-up after discharge, no recurrence or any complication was observed. Conclusion:rhTNFR:Fc is effective and safe for the treatment of drug-induced TEN.

Objective: The aim of this study was to evaluate the value for CBL and LBL teaching method in the training of refresher doctors in reproductive medicine. Methods: A questionnaire survey was conducted among 186 refresher doctors who had studied in the reproductive medicine center at Peking University Third Hospital from January 2016 and December 2017 one year after their graduation. We tested 33 refresher doctors in observe group and 33 refresher doctors in the CBL+LBL group who graduated at the same period. Results: Ninety-two refresher doctors responded to the investigation. The questionnaire survey showed that 84.78% of the refresher doctors thought that CBL and LBL teaching method could improve their learning abilities, clinical problem analysis and solving skills, and surgical techniques, which was conducive to promoting their assisted reproductive technology. Besides, 63.04% of refresher doctors believed this method improved their research abilities. In CBL+LBL group, examination scores of theoretical knowledge were significantly higher than the observe group (P<0.05). Conclusion The combination of CBL and LBL is effective and feasible in the training of refresher doctors in reproductive medicine.

Objective To summarize the pathological survey of time-zero renal biopsy (T0-RBx ) . Methods The material qualities and pathological features were analyzed retrospectively for T 0-RBx (n=176) between March 2008 and May 2016 .According to the source of donor kidney ,T0-RBx specimens were divided into living donors (LD) group (n=137) and Deceased donation (DD) group (n=39) .Furthermore , the DD group was divided into cerebral hemorrhage group (n= 10) and brain trauma group (n= 29) according to the causes of death .The inter-group differences of pathological characteristics and the effects of abnormal pathological lesions on allograft function were observed .Results All T0-RBx specimens contained cortical kidney tissue .The average microscopic length of renal tissue was (0 .39 ± 0 .23) cm and the median glomerular number 11 . The abnormal pathological lesions included glomerulosclerosis (GS ,30 .7 ％ ) , segmental glomerulosclerosis (1 .1 ％ ) ,mesangial increase (MI ,19 .3 ％ ) ,tubular atrophy (TA ,35 .2 ％ ) , acute tubular necrosis (ATN ,9 .1 ％ ) ,vacuolar degeneration of tubular epithelium (27 .3 ％ ) ,losses in tubule epithelial brush border (97 .7 ％ ) , protein cast (25 ％ ) , interstitial fibrosis (IF ,34 .1 ％ ) , inflammation (I ,42 .6 ％ ) ,arteriolar hyalinosis (AH) (26 .1 ％ ) and vascular fibrous intimal thickening (CV ,23 .3 ％ ) .Among them ,23 .9 ％ ,1 .1 ％ ,0 .55 ％ and 0 .55 ％ cases were diagnosed as IgA nephropathy ,immune complex associated with glomerular disease and focal segmental glomerulosclerosis diabetic nephropathy respectively .And the reminders were of ischemic injury .The incidence rates of TA ,IF and I were lower in DD group than those in LD group ( P< 0 .05 ) . However , ATN and vacuolar degeneration of tubular epithelium were higher (P<0 .001) .The incidence of GS was significantly higher in cerebral hemorrhage group than that in brain trauma group (P<0 .01) .No statistical difference existed in other lesions or disease constitution among the groups (P>0 .05) .Further analysis showed GS was related with allograft function at 6/12 months post-transplantation in both LD and DD groups (P<0 .05) .IF and AH were also related to short-term renal function of recipients post-transplantation in LD and DD groups (P>0 .05) .Conclusions T0-RBx may detect the abnormal lesions of donor kidney .Some differences exist in types and degree of abnormal lesions among different donor kidneys .LD group has a higher risk for chronic histological injury such as TA and IF while DD group is more susceptible to acute renal tubular interstitial injury .Thus it is valuable for predicting allograft function post-transplantation .Material quality is essential for ensuring the reliability of T 0-RBx .

Objective The nursing staff's output and journals distribution of core scientific journals papers were analyzed, providing evaluation data and a decisive basis for scientific research management. Methods A retrospective analysis was performed to the publication of core journals papers of nursing staff in 2013-2015 based on the publication from different nursing positions , the ranking of published nursing papers from different departments and different journals by using analysis method of bibliometric. Results About 1550 nursing papers were published , of which the number of authors whose paper was published in core journals was 216 , the number of papers published in core journals was 378, and 38 authors published more than 3 papers (17.6%). The core journals papers published rate in different position was statistically significant (P<0.01). The papers published journals were concentrated in nursing class. Dominated the first 3 places in the list of core journals paper number of departments were department of nursing , cancer center and operation room, respectively. Conclusion In order to improve the nursing scientific research level of nursing staff, it is necessary to establish a theoretical system of scientific knowledge training , formulate a long-term effective mechanism in paper management , focus on scientific research talent introduction and training and mobilize the nursing research enthusiasm of nursing staff.

Objective To design the ISO15189 management information middleware based on laboratory information management system (LIS) and evaluate its application.Methods The ISO15189 management information middleware was designed based on LIS and the middleware technology as underlaying platform,and the multifunction management of LIS was implemented by the data warehouse technology and the data cleaning and extraction technology.Results The designed middleware made LIS implement the functions such as data exchange and transmission,data sharing,and data intelligence processing ISO15189 management information across multiple systems.It constructed a data warehouse by extracting,transforming,and loading useful data from multiple profession systems in laboratories,and flexibly presented data to the users by operating multidimensional data set from various aspects.Conclusion The ISO15189 management information middleware based on LIS has high value in the management of ISO15189 accredit,which may make the management work more standard,efficiency,and intelligence.