AIM: To investigate the effect of ligustrazine on hydrogen sulfide (H_2S) system in pulmonary hypertension induced by hypoxic hypercapnia in rats. METHODS: Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C), hypoxic hypercapnia group (HH), and hypoxic hypercapnia+ligustrazine group (HH+L). The change of hemodynamics was measured. The ratio of vessel wall area and total area of arteriae pulmonalis were observed under light microscope. The apoptosis of arteriae pulmonalis was tested with TdT-mediated dUTP nick end labeling (TUNEL), and the apoptosis index was calculated. Plasma level of hydrogen sulfide and activity of hydrogen sulfide generating enzymes in homogenates of rat lung tissue were evaluated by sensitive modified sulfide electrode method. Cystathionine-γ-lyase (CSE) mRNA in lung tissues was determined by RT-PCR. RESULTS: The level of mean pulmonary arterial pressure, the ratio of vessel wall area/total area and the right ventricle/left ventricle+septum were significantly higher in HH group than those in C group, and the value was obviously lower in HH+LTZ group than that in HH group (all P<0.01). The mean carotid arterial pressure of 3 groups had no significant difference (P>0.05). The apoptotic index of arteriae pulmonalis in HH group and HH+LTZ group was significantly lower than that in C group, and that in HH+LTZ group was significantly higher than that in HH group (P<0.05 or P<0.01). Plasma level of H_2S, the activity of H_2S generating enzymes in homogenates of rat lung tissue, cystathionine-γ-lyase (CSE) mRNA in lung tissues in HH group were significantly lower than those in C group (all P<0.01), and those in HH+LTZ group were significantly lower than those in HH group (all P<0.01). CONCLUSION: Ligustrazine up-regulates the expression of cystanthionine-γ-splitting enzyme (CSE), enhances the activity of CSE and increases the level of H_2S to prevent pulmonary hypertension induced by hypoxic hypercapnia.

Objective To explore the effects of oscillating blood glucose on apoptosis in renal tubular epithelial cells of diabetic rats and the role of oxidative stress.Methods Renal tubular epithelial cells (HK-2) were cultured in vitro with stable high glucose or oscillating high glucose,and MTF assay was applied to the neasurement of cell proliferation.Streptozotocin induced diabetic model was established with SD rats and the oscillating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time points every.day.12 weeks later 24 h urine protein (24hUP),blood urea nitrogen (BUN),serum creatinine (Scr),superoxide dismutase (SOD), and malondialdehyde (MDA)were determined. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),and immunohisto-chemistry was used to detect apoptosis associated gene Bax,Bcl-2,and NOX-4 expression in kidney.Changes in ultrastructure were observed.Results Oscillating high glucose may inhibit renal cells proliferation obviously when comparing with stable high glucose.In the rats with oscillating blood glucose rather than those with stable high blood glucose,there was a significant increase of BUN,Scr,24hUP,and MDA and a decrease of SOD[ (21.50 ± 1.72 vs 12.50 ± 1.85 )mmol/L,(97.51 ± 7.84 vs 82.12 ± 11.48 ) μmol/L,( 1.57 ± 0.09 vs 1.04 ± 0.12 ) mg/24 h,( 23.50 ± 1.87 vs 14.82 ± 2.96) nmol/ml,( 17.22 ± 1.12 vs 21.11 ± 1.80) U/ml,all P＜0.05 ] ; cell apoptosis was intensified with the up-regulation of Bax and NOX-4 protein expression and down-regulation of Bcl-2 in glomerular endothelial cells; and more severe pathological damages were observed.ConclusionComparing with stable high blood glucose,oscillating high blood glucose induces more apoptosis and less proliferation of renal tubular epithelial cells and the mechanism may be related to the increased oxidative stress.

Objective To analyze the discrepancy and similarities of clinical characteristics in elderly patients with ulcerative colitis (UC) and ischemic colitis (IC).Methods A total of 43 elderly patients (age≥60 yrs) with UC and 36 elderly patients with IC were enrolled from 2004 to 2015 at Peking Union Medical College Hospital.The clinical characteristics were retrospectively analyzed and compared between the two groups.Results Compared with IC group,the disease course was longer with lower incidence of cardiovascular comorbidities in UC patients (P ＜ 0.05).In UC group,more patients presented with diarrhea,mucopurulent bloody stool [39 (90.7％) vs 16 (44.4％) and 34 (79.1％) vs 2 (5.6％)respectively,both P ＜ 0.01].Yet bloody stool as the only symptom was seen in more IC patients than UC patients [61.1％ (22/36) vs 7.0％ (3/43),P ＜ 0.01].The ratio of extra-intestinal manifestations was higher [18.6％ (8/43) vs 0 (0/36)] in UC patients,while complications were lower [11.6％ (5/43) vs 30.6％ (11/36),P ＜ 0.05].As to the laboratory parameters,median platelet count [(294.38 ± 104.83) × 109/L vs (235.47±94.82) × 109/L,P ＜0.05] was higher in UC group.In addition,more patients with UC had positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) [50.0％ (15/30) vs 10.0％ (2/20),P ＜ 0.05].The most commonly involved regions of IC were descending colon and sigmoid colon,in which the lesions were clearly demarcated with the normal mucosa.Lesions in patients with UC mainly originated from rectum and might spread to the whole colon.Vascular occlusion and micro thrombosis were characteristic pathological findings of IC.The crypt abscesses were frequently seen in the UC group.Conclusion Even though UC and IC have some similar manifestations in the elderly patients,clinical and pathological discrepancy is still helpful to differentiate each other.

AIM:To investigate the effect of L-arginine(L-Arg) on expression of bcl-2,bax mRNA during pulmonary ischemia and reperfusion injury(PIRI) in rabbits.METHODS: Single lung ischemia and reperfusion animal model was used in vivo.The rabbits were randomly divided into three groups: sham operated group(sham,n=12),ischemia-reperfusion group(I/R,n=12) and I/R+ L-arginine group(L-Arg,n=12).Changes of several parameters,which included apoptotic index(AI),wet to dry ratio of lung tissue weight(W/D) and index of quantitative assessment of histologic lung injury(IQA),were measured at 300 min after reperfusion in lung tissue.Meanwhile the location and expression of bcl-2,bax mRNA as well as the ratio of bcl-2 mRNA/bax mRNA were observed.The lung tissue was prepared for light microscopic and electron microscopic observation at 60,180 and 300 min after reperfusion.RESULTS: As compared with I/R group,in intima and extima of small pulmonary artery,alveoli,and bronchiole epithelia,the expression of bcl-2 mRNA and the ratio of bcl-2 mRNA/bax mRNA were increased,and the expression of bax mRNA was decreased in L-Arg treatment group.The values of AI,W/D and IQA showed significantly lower than that in I/R group at 180 minutes after reperfusion in lung tissue(P

Objective:To investigate the effects of metformin on the survival of patients with advanced non-small cell lung cancer (NSCLC).Methods:PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and other databases were searched from the beginning of database construction to February 2020, relevant literatures were screened and included, and the characteristics of the literatures were extracted. RevMan 5.3 software was used to analyze progression-free survival (PFS), overall survival (OS), hazard ratio(HR) and 95% CI; the heterogeneity and publication bias were also evaluated. Results:A total of 11 studies were enrolled, and metformin did not improve PFS in patients with advanced NSCLC ( HR = 0.80, 95% CI 0.58-1.09, P = 0.15). The subgroup analysis results of different treatment strategies showed that metformin combined with tyrosine kinase inhibitor (TKI) ( HR = 0.71, 95% CI 0.32-1.57, P = 0.39), chemoradiotherapy ( HR = 0.97, 95% CI 0.59-1.61, P = 0.92), and immune checkpoint inhibitor (ICI) ( HR = 0.64, 95% CI 0.35-1.16, P = 0.14) did not improve the PFS. Metformin improved OS in patients with advanced NSCLC ( HR = 0.84, 95% CI 0.75-0.93, P = 0.001). Metformin combined with TKI ( HR = 0.68, 95% CI 0.38- 1.22, P = 0.19) and ICI ( HR =0.80, 95% CI 0.39-1.63, P = 0.54) did not improve OS of patients, while metformin combined with chemoradiotherapy could improve OS ( HR = 0.85, 95% CI 0.78-0.93, P < 0.01). No evidence of publication bias was shown in the funnel plot analysis. Conclusions:Metformin can prolong OS time in patients with advanced NSCLC, especially in patients undergoing metformin combined with radiotherapy and chemotherapy, or concurrent chemoradiotherapy.

Objective:To investigate the quality of humanistic care for nursing students in Hebei province and to analyze its influencing factors.Methods:The humanistic care quality assessment scale of nursing students was designed and used as the research tool. A questionnaire survey was conducted among 2 693 nursing students from 11 medical colleges and universities in Hebei province and the results were analyzed. SPSS 21.0 was used for statistical analysis. Measurement data were expressed by (mean±standard deviation). The single factor analysis of variance and independent sample t-test were used for comparative study, and the multiple linear regression method was used to analyze the influencing factors. Results:The total Cronbach's coefficient of the scale was 0.966, and the Cronbach's coefficient of each dimension was 0.780-0.959, proving that the scale could be used. The data showed that the overall quality of humanistic care of nursing students in Hebei province was (119.70 ± 15.35), and the overall score rate was 85.50%. Among them, the comparison results of education background, grade, participation in volunteer activities, personality, the degree of concern of surrounding people, family atmosphere, and whether the teacher mentioned humanistic care were statistically significant ( P<0.05). Conclusion:The quality of humanistic care for nursing students in Hebei province is at a relatively high level. Colleges and universities can provide targeted education according to the current situation and influencing factors, create a good humanistic classroom atmosphere for nursing students, encourage nursing students to actively participate in humanistic practice, and improve the quality of humanistic care for nursing students.

Tumor extracellular matrix (ECM) is the center component of tumor microenvironment (TME), ECM diversity constitutes the inherent heterogeneity of TME that contributes to tumor growth, dormancy, drug resistance, and metastasis. Discoidin domain receptor 1 is one of the ECM receptors that interact with multiple ECM ligands. It also regulates the occurrence and development of tumors. Accordingly, DDR1 plays an increasingly important role in the prevention, diagnosis, and treatment of cancer. In this review, we primarily summarize the research of ECM and its receptors with components, regulation, cell receptors, and signaling pathways in tumor progression.

Objective To evaluate the testing capabilities of laboratories,analyze existing issues,and improve testing quality,through carrying out the external quality assessment(EQA)of clinical laboratories for human papillomavirus(HPV)type 6 and 11 nucleic acid detection.Methods EQA plan was carried out twice a year.Each panel contains 4 positive samples,including one strong positive sample and one weak positive sample of HPV6 and HPV11,made from cervical secretions from patients with clinical manifestations of condyloma acuminata(CA)and positive for HPV6 or HPV11(from Shanghai First Maternity and Infant Hospital).One negative sample was cultured from the C-33A cell line(from Chinese Academy of Sciences).Samples were sent to participating laboratories by cold chain,and laboratories were required to detect test samples and upload their results within the specified time.Shanghai Center for Clinical Laboratory(SCCL)calculated the scores of each laboratory based on the return results.Results A total of 163 sample panels were sent out in the 6 rounds of EQA plan and 140 valid reports were received.The laboratory qualification rate was 96.43%(135/140)and the sample compliance rate was 97.86%(685/700).There were 13 false negative results and 2 false positive results,with weakly positive samples accounting for 76.92%(10/13)of the false negative results.Conclusion The detection accuracy of HPV6/11 nucleic acid in each laboratory was relatively high,and the detection ability of weak positive samples in individual laboratories may need to be improved.The laboratory could discover problems and improve its quality management by participating in EQA.

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 performance of MTHFR 677 genotyping external quality assessment ( EQA) program using plasmid DNA constructed in vitro as quality control samples and discuss the problems in clinical laboratories enrolled in the program .Methods Recombinant plasmid carrying MTHFR 677C locus sequence was constructed as wild type sample and plasmid with MTHFR 677T mutation was generated with site-directed mutagenesis as mutant type sample .Heterozygous mutant samples were obtained after equal proportion of the two plasmids .EQA scheme were held twice a year in 2016 and 2017, and sample panels contained 5 different samples using recombinant plasmid DNA containing all types of MTHFR 677 locus genotypes.Participating laboratories were asked to test samples using their routine methods and report the results before deadlines .26, 28, 52 and 56 effective reports were received respectively in the four EQA schemes .The scores of each lab were calculated based on their results and the overall compliance of different samples as well as the sensitivity and specificity of different methods were calculated using Microsoft Excel .Results MTHFR 677 locus genotypes of the constructed plasmid were verified by Sanger sequencing and there was no failure of sample detection in the four EQA schemes , which suggest that the plasmid has good clinical applicability .About 96.15％( 25/26 ) ,100％( 28/28 ) ,96.15％ (50/52)and 98.21％(55/56) of the laboratories submitted correct results for all samples in the four EQA schemes.The overall compliance rate were 99.23％ ( 129/130 ) , 100％( 140/140 ) ,96.92％ ( 252/260 ) and 98.93％(277/280) respectively.All laboratories using digital FISH and microarrays got full marks in four EQA schemes.The compliance rates for fluorescent PCR were 97.5％ ( 39/40 ) , 100％ ( 45/45 ) , 94.29％(66/70) and 100％ (95/95) respectively, while the rates were 100％ (20/20), 100％ (15/15), 90％(36/40) and 92.5％(37/40) for Sanger sequencing.Conclusions The recombinant plasmid DNA constructed in this study can effectively detect the performance of reagents with good clinical applicability.The results of EQA programs suggested that the overall accuracy rate of laboratories enrolled was high enough , while some laboratories′performance still needs to be improved .Quality controls in clinical laboratories were essential to assure the accuracy of results .