Influencing Factors of HIV/ AIDS Death Based on Bayesian Cox Proportional Hazard Regression Model / 中山大学学报(医学科学版)

ObjectiveTo understand the composition of related characteristics of HIV/AIDS cases in Lanzhou and analyze the influencing factors of AIDS-related deaths. MethodsThe information of HIV/AIDS cases reported in Lanzhou from 2011 to 2019 was collected， the method of survival was used analysis and Bayesian Cox Proportional Hazard Regression Model was constructed to analyze the related factors of death. ResultsA total of 2 312 HIV/AIDS patients were selected in this study， including 45 AIDS-related deaths. The results of multivariate regression showed that the older the patients were， the higher the risk of death was； the risk of death of AIDS patients at the time of diagnosis was 13.91 times higher than that of HIV-infected patients； Patients who received CD4 testing had a lower risk of death than those who did not； The risk of death was 0.22 times higher among those who received antiretroviral therapy than those who did not receive antiretroviral therapy. ConclusionsAge at diagnosis， course of disease， antiviral therapy were the influencing factors of AIDS-related death in HIV/AIDS patients in Lanzhou. Therefore， it is necessary to strengthen health education for AIDS-related groups， advocate early detection， early diagnosis， and early treatment， expand the coverage of AIDS testing and treatment， prolong the survival time of AIDS patients.

Construction of a novel bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 and evaluation of its immunogenicity in mice / 中华微生物学和免疫学杂志

Objective:To construct a bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 and to evaluate its immunogenicity in mice.Methods:The coding sequences for spike 1 (S1) protein of SARS-CoV-2 Beta variant and hemagglutinin (HA) of influenza A virus Cambodia (H3N2) strain were codon-optimized and synthesized. The two coding genes were ligated by the self-cleaving 2A peptide using over-lapping PCR to construct S1-2A-HA fragment, which was inserted into pVRC vector to construct the bivalent DNA vaccine, named as pVRC-S1-2A-HA. Indirect immunofluorescence assay (IFA) and Western blot were performed to detect the expression of S1 and HA proteins. BALB/c mice were immunized with pVRC-S1-2A-HA by intramuscular injection and electroporation. The humoral immune responses induced in mice were detected by indirect ELISA, pseudovirus neutralization assay and hemagglutination inhibition assay. Cellular immune responses were detected by IFN-γ ELISPOT, intracellular cytokine staining (ICS) and cytometric bead array (CBA).Results:The bivalent DNA vaccine pVRC-S1-2A-HA could express S1 and HA proteins in vitro. Specific cellular immune responses against S1 protein and specific IgG antibody against HA protein were significantly induced in mice with single-dose immunization. The antigen-specific immunity was significantly enhanced after booster immunization. The geometric mean titer (GMT) of specific IgG antibody increased to 3 251 for S1 protein and 45 407 for HA protein after two-dose immunization. Moreover, the S1-specific T cells increased to 1 238 SFC/10 6 cells. ICS results indicated that the booster vaccination induced CD4 + T and CD8 + T cells to produce IL-2, IFN-γ and TNF-α in mice. The secretion of various cytokines including IL-2, IL- 4, IL-6, IL-10 and IFN-γ in mouse splenocytes was induced after single-dose immunization. Conclusions:A bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 was constructed and could induce S1- and HA-specific humoral and cellular immune responses in mice, suggesting the great potential of it for further development and application.

Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells / 中国中药杂志

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

Diversity-oriented synthesis of marine sponge derived hyrtioreticulins and their anti-inflammatory activities / 中国天然药物

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.

The influence of glucose regulatory protein 78 on prognosis and tumor cell proliferation of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the influence of glucose regulatory protein 78 (GRP78) on prognosis and tumor cell proliferation of hepatocellular carcinoma.Methods:The experimental study and retrospective cohort study were conducted. Based on hepatocellular carcinoma tissue chip, in vitro culture of Huh7 and Hep3B hepatoma cells and LO2 normal hepatic cell, and combined with immunohistochemical staining, cell transfection, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot detection, cell proliferation experiments, cell clone formation experiments and high-throughput transcription histological analysis, the GRP78 expression in hepatoma cells was analyzed. Huh7 and Hep3B hepatoma cells being transfected with the GRP78 gene-specific shRNA lentiviruses or the negative control shRNA lentivirus were set as the GRP78 gene-specific shRNA lentivirus group and the negative control shRNA lentivirus group respectively. Observation indicators: (1) GRP78 expression in hepatocellular carcinoma tissue and adjacent tissue and its correlation with the clinicopathological characteristics of hepatocellular carcinoma patients; (2) analysis of factors affecting the prognosis of hepatocellular carcinoma patients; (3) effects of inhibiting of GRP78 expression on the proliferation of hepatoma cells; (4) effects of inhibiting of GRP78 expression on the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells; (5) effects of HA15 on the proliferation and the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells. Measurement data of the normal distribution were expressed as Mean± SD, and comparison of groups was conducted using the t test or ANOVA. Repeated measurement data were analyzed using repeated ANOVA. Count data were expressed as absolute numbers, and comparisons between groups was conducted using the chi-square test. COX proportional hazards regression model was used for univariate and multivariate analysis. The Kaplan-Meier method was used to calculate the survival time and draw survival curve, and the Log-rank test was used for generative analysis. Results:(1) GRP78 expression in hepatocellular carcinoma tissue and adjacent tissue and its correlation with the clinicopathological characteristics of hepatocellular carcinoma patients: results of immunohistochemical staining of hepatocellular carcinoma tissue chip showed that GRP78 was low-expressed in 53 cases and high-expressed in 37 cases of the 90 hepatocellular carcinoma tissues. GRP78 was low-expressed in 84 cases and high-expressed in 6 cases of the 90 paracancerous tissues. There was a significant difference in GRP78 expression between hepatocellular carcinoma tissues and paracancerous tissues ( P<0.05). (2) Analysis of factors affecting the prognosis of hepatocellular carcinoma patients: all 90 patients were followed up for 5 to 56 months, with a median follow-up time of 49 months. The median overall survival time and median disease progression-free survival time were 56 months and 53 months in the 53 hepatocellular carcinoma patients with GRP78 as low-expressed, versus 32 months and 19 months in the 37 hepatocellular carcinoma patients with GRP78 as high-expressed, respec-tively, showing significant differences ( χ2=17.482, 12.097, P<0.05). Results of univariate analysis showed that alanine aminotransferase (ALT), tumor pathological grading and GRP78 expression were related factors affecting the 3-year overall survival rate and disease progression-free survival rate of hepatocellular carcinoma patients ( hazard ratio=2.317, 2.039, 3.740 and 2.194, 2.177, 2.927, 95% confidence interval as 1.150?4.671, 1.201?3.462, 2.116?6.612 and 1.048?4.593, 1.093?4.336, 1.492?5.742, P<0.05). Results of multivariate analysis showed that ALT >40 U/L, tumor pathological grading as Ⅲ-Ⅳ grade and GRP78 as high-expressed were independent risk factors affecting the 3-year overall survival rate and disease progression-free survival rate of hepatocellular carcinoma patients ( hazard ratio=2.438, 2.245, 3.223 and 3.046, 2.473, 3.307, 95% confidence interval as 1.114?5.334, 1.047?4.814, 1.396?7.440 and 1.337?6.940, 1.141?5.360, 1.399?7.819, P<0.05). (3) Effects of inhibiting of GRP78 expression on the proliferation of hepatoma cells: ①results of qRT-PCR showed that the relative expression of GRP78 messenger RNA (mRNA) in Huh7, Hep3B, and LO2 cells were 3.06±0.33, 4.42±0.60 and 1.00±0.02. There were significant differences in GRP78 mRNA expression between Huh7 and LO2 cells or Hep3B and LO2 cells ( t=6.19, 5.42, P<0.05). ②Results of Western Blot detection showed that the relative expression of GRP78 protein in Huh7, Hep3B, and LO2 cells were 1.65±0.01, 1.77±0.01 and 0.99±0.02. There were significant differences in GRP78 protein expression between Huh7 and LO2 cells or Hep3B and LO2 cells ( t=75.09, 108.10, P<0.05). ③Results of cell proliferation experiments showed that the growth rates in Hu7 GRP78 gene-specific shRNA lentiviruses group cells and Hu7 negative control shRNA lentivirus group cells at 24, 48, 72 and 96 hours were 111.51%±0.35%, 144.85%±0.68%, 188.71%±3.62%, 282.51%±5.25% and 190.08%±0.58%, 285.76%±2.69%, 459.51%±4.29%, 597.88%±12.25%, showing signifi-cant differences ( Fgroups=1 360.000, Ftime=668.500, Finteraction=197.600, P<0.05). The growth rates in Hep3B GRP78 gene-specific shRNA lentiviruses group cells and Hep3B negative control shRNA lentivirus group cells at 24, 48, 72 and 96 hours were 124.47%±0.25%, 153.25%±1.25%, 195.45%±3.19%, 282.51%±10.76% and 179.69%±0.33%, 322.67%±2.46%, 486.27%±5.82%, 622.35%±12.58%, showing significant differences ( Fgroups=1 222.000, Ftime=706.200, Finteraction=179.600, P<0.05). ④Results of the cell clone formation experiments showed that the number of cells in Hu7 GRP78 gene-specific shRNA lentiviruses group cells and Hu7 negative control shRNA lentivirus group cells were 125±3 and 435±17, showing a significant difference ( t=17.86, P<0.05). The number of cells in Hep3B GRP78 gene-specific shRNA lentiviruses group cells and Hep3B negative control shRNA lentivirus group cells were 138±3 and 388±7, showing a significant difference ( t=32.29, P<0.05). (4) Effects of inhibiting of GRP78 expression on the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells: results of high-throughput transcription histological analysis showed that the relative expression rates of p53, p21, CDK2, CDK4, and CDK6 were 19%, 334%, 398%, 41% and 49% in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells comparing to the Hu7 negative control shRNA lentivirus group cells. ①Results of qRT-PCR showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.17±0.03, 4.05±0.71, 3.73±0.47, 0.49±0.09, 0.48±0.06, 0.36±0.07 in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells, versus 1.00±0.05, 1.03±0.17, 1.00±0.07, 1.01±0.09, 1.02±0.14, 1.00±0.03 in the Hu7 negative control shRNA lentivirus group cells, showing significant differences ( t=14.62, 4.17, 5.72, 4.26, 3.49, 8.82, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.11±0.01, 4.28±0.43, 4.19±0.22, 0.44±0.01, 0.25±0.03, 0.68±0.04 in Hep3B GRP78 gene-specific shRNA lentiviruses group cells, versus 1.01±0.09, 1.02±0.15, 1.00±0.06, 1.01±0.09, 1.01±0.08, 1.15±0.02 in Hep3B negative control shRNA lentivirus group cells, showing significant differences ( t=10.19, 7.14, 13.79, 6.37, 9.42, 9.61, P<0.05). ②Results of Western Blot detection showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.45±0.01, 1.98±0.05, 2.31±0.12, 0.75±0.03, 0.69±0.04, 0.82±0.03 in the Hu7 GRP78 gene-specific shRNA lentiviruses group cells, versus 1.01±0.05, 1.03±0.01, 1.00±0.02, 1.00±0.01, 1.01±0.02, 1.00±0.03 in the Hu7 negative control shRNA lentivirus group cells, showing significant differences ( t=11.07, 14.56, 11.30, 11.29, 10.55, 11.37, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.61±0.03, 1.98±0.16, 2.55±0.12, 0.85±0.03, 0.78±0.01, 0.54±0.02 in Hep3B GRP78 gene-specific shRNA lentiviruses group cells, versus 1.00±0.03, 1.05±0.02, 1.05±0.01, 1.05±0.02, 1.00±0.02, 1.00±0.02 in Hep3B negative control shRNA lentivirus group cells, showing significant differences ( t=10.97, 13.40, 12.35, 11.06, 12.45, 13.78, P<0.05). (5) Effects of HA15 on the proliferation and the gene and protein expression of p53, p21, CDK2, CDK4, and CDK6 in hepatoma cells: results of 50% inhibiting concentration (IC50) test of HA15 showed that the IC50 of HA15 for Huh7 and Hep3B cells at 48 hours were 9.98 μmol/L and 13.70 μmol/L. ①Huh7 and Hep3B cells were treated with 9.98 μmol/L and 13.70 μmol/L of HA15. Results of cell proliferation experiments showed that the growth rates at 24, 48, 72, and 96 hours were 112.81%±0.27%, 154.71%±1.45%, 237.66%±16.77%, 294.40%±14.92% in the HA15-Huh7 cells, versus 133.67%±0.49%, 352.93%±2.31%, 557.17%±4.89%, 662.60%±13.31% in the normal Huh7 cells, showing a significant difference ( Fgroups=766.800, Ftime=518.200, Finteraction=133.300, P<0.05). The growth rates at 24, 48, 72, and 96 hours were 121.27%±2.32%, 203.85%±3.18%, 240.80%±3.02%, 286.50%±7.10% in the HA15-Hep3B cells, versus 239.14%±1.02%, 362.00%±5.44%, 539.37%±10.80%, 694.79%±17.13% in the normal Hep3B cells, showing a signifi-cant difference ( Fgroups=594.300, Ftime=317.900, Finteraction=78.600, P<0.05). ②Results of qRT-PCR showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.27±0.05, 3.64±0.28, 4.13±0.41, 0.51±0.07, 0.39±0.03, 0.17±0.02 in the HA15-Huh7 cells, versus 1.02±0.14, 1.00±0.03, 1.00±0.05, 1.01±0.08, 1.01±0.09, 1.03±0.17 in the normal Huh7 cells, showing significant differences ( t=5.00, 9.25, 7.63, 4.73, 6.82, 5.01, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 mRNA were 0.28±0.03, 3.49±0.78, 4.31±0.53, 0.38±0.05, 0.36±0.04, 0.24±0.03 in the HA15-Hep3B cells, versus 1.01±0.11, 1.03±0.18, 1.01±0.08, 1.00±0.06, 1.02±0.15, 1.00±0.06 in the normal Hep3B cells, showing significant differences ( t=6.26, 3.08, 6.21, 7.97, 4.26, 11.08, P<0.05). ③Results of Western Blot detection showed that the relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.52±0.05, 1.94±0.08, 1.58±0.02, 0.89±0.00, 0.86±0.02, 0.74±0.01 in the HA15-Huh7 cells, versus 1.02±0.03, 1.00±0.03, 1.02±0.02, 1.04±0.03, 1.00±0.01, 1.01±0.02 in the normal Huh7 cells, showing significant differences ( t=11.54, 10.28, 11.03, 12.81, 13.67, 10.09, P<0.05). The relative expression of GRP78, p53, p21, CDK2, CDK4, and CDK6 protein were 0.57±0.02, 1.67±0.04, 1.41±0.04, 0.82±0.03, 0.70±0.02, 0.74±0.01 in the HA15-Hep3B cells, versus 1.03±0.01, 0.98±0.03, 1.00±0.03, 1.03±0.03, 1.01±0.01, 1.04±0.01 in the normal Huh7 cells, showing significant differences ( t=10.81, 11.54, 12.26, 13.62, 14.23, 10.17, P<0.05). Conclusions:High expression of GRP78 is an independent risk factor affecting the overall survival and disease progression-free survival of hepatocellular carcinoma patients. Inhibiting of GRP78 expression can reduce cell proliferation and the expression of p53, p21, CDK2, CDK4, and CDK6 mRNA and proteins in hepatoma cells.

Genetic analysis of 46,XY disorders of sex development in children caused by a new NR5A1 gene variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with 46,XY disorders of sex development (DSD) and explore its genotype-phenotype correlation.@*METHODS@#The child was subjected to whole exome sequencing (WES), and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis.@*RESULTS@#The patient presented with rudimentary vulva of a female with Tanner stage 1. B-mode ultrasonography has detected ovary and uterus. The child was found to have a chromosome karyotype of 46,XY. WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene, which was a novel pathogenic variant inherited from the mother. No abnormality was found in the father.@*CONCLUSION@#The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization, for which variants of the NR5A1 gene are an important cause. WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.

Correlation between genotypes with metabolic markers and microstructure of bones in children with Gitelman syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS).@*METHODS@#For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes.@*RESULTS@#The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls.@*CONCLUSION@#The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.

Effectiveness and safety of epinephrine and norepinephrine for treating non-variceal upper gastrointestinal bleeding: a meta-analysis / 中华消化内镜杂志

Objective:To systematically evaluate the effectiveness and safety of epinephrine injection and norepinephrine spraying for treating non-variceal upper gastrointestinal bleeding.Methods:Databases including the PubMed, Embase, Cochrane Library, CNKI, CBM, VIP and WanFang Data with the retrieval time from inception to December 2018 were searched to collect the related clinical trials. The references of included studies were also retrieved. Studies were screened, data were extracted, and the risk of bias was assessed by 2 reviewers separately. The meta-analysis was conducted by using RevMan 5.3 software. The grading of recommendations, assessment, development and evaluation (GRADE) quality of evidence system was used to assess the results of meta-analysis.Results:A total of 10 studies involving 884 participants were included. The results showed that compared with the norepinephrine spraying, epinephrine injection was superior in the following aspects with significant differences: the effective rate ( RR=1.21, 95% CI: 1.12-1.30, P<0.001); the one-week recurrent bleeding rate ( RR=0.28, 95% CI: 0.17-0.45, P<0.001); the immediate hemostatic rate ( RR=1.38, 95% CI: 1.25-1.52, P<0.001); and the emergent operation rate ( RR=0.35, 95% CI: 0.19-0.63, P<0.001). Conclusion:Epinephrine injection is more effective and safer for treating non-variceal upper gastrointestinal bleeding in comparison with norepinephrine spraying.

Clinical efficacy of different treatments and their impacts on the quality of life of octogenarians with coronary artery disease / 中华医学杂志(英文版)

BACKGROUND@#Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD.@*METHODS@#Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis).@*RESULTS@#The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204).@*CONCLUSION@#PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.

Clinical efficacy of different treatments and their impacts on the quality of life of octogenarians with coronary artery disease / 中华医学杂志(英文版)

Background@#Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD.@*Methods@#Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis).@*Results@#The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ2 = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204).@*Conclusion@#PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.

Analysis of early clinical efficacy of renal transplantation from extended criteria donor of the donation after cardiac death / 器官移植

Objective To compare the early clinical efficacy of renal transplantation between extended criteria donor (ECD) and standard criteria donor (SCD). Methods Clinical data of 85 recipients undergoing renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the types of donors, all recipients were divided into the ECD group (n=31) and SCD group (n=54). The level of serum creatinine (Scr), incidence of early complications and clinical prognosis within 3 months after renal transplantation were compared between 2 groups. Results No statistical significance was observed in the levels of Scr within 1 month after renal transplantation between the ECD group and SCD group (all P>0.05). At postoperative 60 and 90 d, the level of Scr in the ECD group was (189±97) and (175± 69) μmol/L respectively, significantly higher than (142±49) and (135±41) μmol/L in the SCD group (P=0.005 and 0.002). In the ECD group and SCD group, the incidence of acute rejection (AR) was 6% and 15%, the incidence of delayed graft function (DGF) was 23% and 19%, the incidence of pulmonary infection was 10% and 6%, the incidence of other early complications was 32% and 15%, respectively, no statistical significance was identified (all P>0.05). In the ECD group and SCD group, the survival rate of the recipient was 97% and 94%, the survival rate of the renal was 84% and 91%, no statistical significance was identified (all P>0.05). Conclusions Compared with the SCD, renal transplantation from ECD can achieve equivalent early clinical efficacy. In the present condition of serious deficiency of donor kidney, the application of ECD can enlarge the supply of the donor kidney.

Effects of braln-derived neurotrophic factor-modified human amniotic membrane-derived mesenchymal stem cell transplantation on learning and memory abilities of alzheimer's disease rats / 中国组织工程研究

BACKGROUND: A variety of stem cells have been found to be effective in the treatment of Alzheimer's disease in rats. However, few reports have been reported on the treatment of Alzheimer's disease rats with brain-derived neurotrophic factor (BDNF)-modified human amniotic membrane-derived mesenchymal stem cells. OBJECTIVE: To investigate the effects of BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation on the learning and memory abilities of Alzheimer's disease rats. METHODS: Forty-eight Sprague-Dawley rats were divided into control group (no treatment), model group (Alzheimer's disease model), stem cell transplantation group (human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model) and BDNF-modified stem cell transplantation group (BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model), 12 rats in each group. Learning and memory of model rats were determined in a trisection radiation maze and immunohistochemical staining was used to determine the number of p75 positive neurons at 2 weeks after cell transplantation. RESULTS AND CONCLUSION: The number of p75 positive neurons in the bevel zone and medial septal nucleus was ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). The learning and memory abilities of the rats were ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). In the BDNF-modified stem cell transplantation group, the number of learnings was negatively correlated with the number of p75 NGFR-positive neurons (P < 0.05), while the memory capacity was positively correlated with the number of p75 NGFR-positive neurons (P < 0.05). These findings reveal that human amniotic membrane-derived mesenchymal stem cell transplantation can improve learning and memory abilities of Alzheimer's disease rats, and BDNF-modified human amniotic membrane-derived mesenchymal stem cells can further improve this therapeutic effect.

Effect of acupuncture in intervening heroin-induced brain damage via regulating ubiquitin-proteasome pathway / 针灸推拿医学（英文版）

Objective:To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway (UPP),and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods:Thirty male Sprague-Dawley (SD) rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui (GV 20) and Dazhui (GV 14) at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area (VTA) of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL).The mRNA and protein expressions of ubiquitin (Ub),ubiquitin protein ligase (E3) and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR).Results:Compared with the model group,rat's hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining (P＜0.01),and its mRNA and protein expressions of Ub,E3,26S were significantly lower (P＜0.01).Conclusion:Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat's hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.

A study on the IFIH1 gene polymorphism in children with type 1 diabetes in Tianjin area / 中华内分泌代谢杂志

The blood samples of 102 type 1 diabetic children aged under 15 years and 127 normal children were collected and their genomic DNAs were extracted. The single nucleotide polymorphisms rs1990760 and rs35744605 of interferon induced with helicase C domain 1(IFIH1)gene were detected. The results showed that the allele of IFIH1 rs35744605 in diabetes group and control group was the wild type G allele. The frequency of IFIH1 rs1990760 A allele in diabetes group was higher than that in control group(22. 1％ vs 13. 0％ ,P=0. 015), suggesting that IFIH1 rs1990760 A allele is associated with type 1 diabetes in Tianjin area.

Recent research advances of 1-deoxynojirimycin and its derivatives / 中国中药杂志

The 1-DNJ named 1-deoxynojirimycinis (2R,3R,4R,5S)-2-(hydroxymethyl) piperidine-3,4,5-triol, which is the nature active components existingin mulberryresources including leaves, stems, roots and silkworm larva, silkworm chrysalis, etc.The 1-deoxynojirimycin is a polyhydroxylated piperidine alkaloid, which was first found in Streptomyces as an antibiotic. Then the Japanese researchers isolated it from the mulberry root. 1-DNJ can inhibit postprandial hyperglycemia by suppressing intestinal alpha glucosidase. Therefore, 1-DNJ is often used to treat treating diabetes and complicating disease and to prevent obesity and weight-related disorders. With the development of the researches, 1-deoxynojirimycin and its derivtiv was discovered to possess anti-hyperglycemic, anti-virus, anti-tumor functions and so on. Therefore,based on our current studythe existing knowledge on source, technique preparation process, pharmacokinetics, bioactivties,and in silico target fishing of 1-DNJ were summarized, so that the researchers may use it to explore future perspective of research on 1-DNJ.

Unfractionated Heparin with Sequential Enoxaparin in Patients with Complex Coronary Artery Lesions during Percutaneous Coronary Intervention / 中华医学杂志(英文版)

<p><b>Background</b>Unfractionated heparin (UFH), despite its limitations, has been used as the primary anticoagulant alternative during the percutaneous coronary intervention (PCI). Some studies indicated that intravenous enoxaparin could be an effective and safe option. Our team used enoxaparin alone at one time according to the guidelines (Class IIA) and found a little catheter thrombosis during PCI. We recommend a new anticoagulation strategy using enoxaparin in combination with UFH. Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI. This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease.</p><p><b>Methods</b>Between January 2015 and April 2017, 600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg (observation group) and 600 PCI patients who received UFH at a dose of 100 U/kg (control group) were consecutively included in this retrospective study. The endpoints were postoperative 48-h thrombolysis in myocardial infarction (TIMI) bleeding and transfusion and 30-day and 1-year major adverse cardio-cerebrovascular events (MACCE).</p><p><b>Results</b>Baseline clinical, angiographic, and procedural characteristics were similar between groups, except there was less stent implantation per patient in the observation group (2.13 vs. 2.25 in the control group, P = 0.002). TIMI bleeding (3.3% vs. 4.7%) showed no significant difference between the observation group and control group. During the 30-day follow-up, the rate of MACCE was 0.9% in the observation group and 1.5% in the control group. There was no significant difference in the rates of MACCE, death, myocardial infarction, target vessel revascularization, cerebrovascular event, and angina within 30 days and 1 year after PCI between groups as well as in the subgroup analysis of transfemoral approach.</p><p><b>Conclusions</b>UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.</p>

Determination of Hydroxyl Radical in Atmosphere by Molecularly Imprinted Electrochemical Sensor / 分析化学

p-Hydroxybenzoic acid can be oxidized by hydroxyl radicals ( · OH) to produce electroactive 3,4-dihydroxybenzoic acid (3,4-DHBA). Therefore, it can be used as a probe to detect ·OH. In this work, 3,4-DHBA/ PPy / TiO2 molecularly imprinted polymer film was prepared for indirect determination of ·OH based on its recognition ability for 3,4-DHBA. The sensor was constructed by using pyrrole as the functional monomer and 3, 4-DHBA as the template molecule. The sensor was characterized by scanning electron microscope and different electrochemical methods. The preparation and determination conditions, such as the electropolymerization cycle number, pH value in the electropolymerization process, and elution time, were optimized. Under the optimal conditions, a linear range of 1. 0×10-8-1. 0×10-6 mol/ L was obtained for 3,4-DHBA and the detection limit was down to 4. 2×10-9 mol/ L (S / N = 3). This new approach was of low cost and convenience, and was successfully applied to measure the concentration of ·OH in the atmosphere.

Clinical study of early infection of multi-drug resistant organisms after renal transplantation from organ donation after citizen's death / 器官移植

Objective To investigate the clinical characteristics, prevention and treatment of multi-drug resistant organisms (MDROs) infection early after renal transplantation from donation after citizen's death. Methods Clinical data of 166 patients undergoing allogeneic renal transplantation and regular follow-up in Xijing Hospital from November 2011 to September 2016 were retrospectively analyzed. General conditions were statistically compared between the recipients undergoing renal transplantation from donation after cardiac death (DCD) and their counterparts receiving living related donor renal transplantation. The incidence of MDROs infection, onset time, course of diseases, complications, infection site and etiological type were observed. The therapeutic methods and clinical prognosis were summarized. Results The incidence of MDROs infection early after renal transplantation in the recipients undergoing DCD renal transplantation was 14%, significantly higher than 2% in those receiving living related donor renal transplantation, and 13% and 2% for the incidence of delayed graft function with statistical significance (both P<0.05). The incidence of renal graft loss was 8%and 2%, and 5% and 1% for the mortality rate without statistical significance between two groups (both P>0.05). MDROs infection occurred in 11 patients after DCD renal transplantation. The most common infection site was urinary system(n=6) and the most prevalent pathogenic bacterium was Escherichia coli (n=4). All patients infected with MDROs were treated with a sufficient dosage of effective antibiotics according to the outcomes of bacterial culture and drug sensitivity test. Eight patients obtained favorable clinical prognosis, one underwent nephrectomy and two died. Conclusions The incidence of MDROs infection early after DCD renal transplantation is higher than that after living related-donor renal transplantation. Strict donor screening, early detection, intimate monitoring and timely treatment can effectively reduce the risk of MDROs and enhance clinical prognosis.

Effect of hypothermia status in donors on renal graft function after renal transplantation from donation after citizen's death / 器官移植

Objective To evaluate the effect of hypothermia status in the donors upon the renal graft function after renal transplantation from donation after citizen's death. Methods Thirty-six eligible donors were randomly divided into the normal temperature (body temperature 36.5-37.5 ℃ , n=19) and hypothermia groups (body temperature 34.0-35.0 ℃ , n=17). The matched recipients undergoing renal transplantation were also assigned into the normal temperature (n=38) and hypothermia groups (n=34). Perioperative conditions of the donors and recipients were compared between two groups. And postoperative renal graft function of the recipients were statistically compared between two groups, including the incidence of delayed graft function (DGF) and primary nonfunction (PNF). Results No statistical significance was identified in the perioperative amount of urine volume, serum creatinine (Scr), systolic blood pressure, saturation oxygen, warm ischemia time and cold ischemia time of the donors between two groups (all P>0.05). No statistical significance was noted in terms of the operation time, intraoperative mean blood glucose and intraoperative mean arterial pressure of the recipients between two groups (all P>0.05). Postoperative incidence of DGF of the recipients in the hypothermia group was 6%, significantly lower than that in the normal temperature group (24%) (χ2=4.393, P=0.036). Postoperative incidence of PNF of the recipients was 3% in both the hypothermia and normal temperature groups with no statistical significance (χ2=0.000, P=1). Conclusions The hypothermia status of the donors can significantly reduce the incidence of DGF, whereas exerts no evident effect upon the incidence of PNF in the recipients.

Lornoxicam,clinical observation and peptide drugs in the treatment of osteoarthritis / 中国生化药物杂志

Objective To investigate the combined use of osteoarthritis treatment effect of lornoxicam and peptide drugs.Methods 260 patients with osteoarthritis treated in our hospital from May 2014 to June 2016 were selected, were randomly divided into study group and control group, each group of 130 cases.The patients in the control group were treated with sodium hyaluronate and lornoxicam, the study group was given bone peptide on the basis of the control group. The pain scores, knee function and adverse reactions were compared between the two groups.Results There was no significant difference in VAS and WOMAC scores between the two groups before treatment; after treatment, the improvement of VAS and WOMAC score in the study group was better than that in the control group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups. Conclusion Sodium hyaluronate, bone peptide, lornoxicam and other drugs in the treatment of patients with osteoarthritis clinical efficacy is obvious, and fewer adverse reactions.