Advances in Salmonella-mediated targeted tumor therapy / 药学学报

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Research on machine learning-based activity prediction models for KRAS inhibitors / 中国药科大学学报

@#Abstract: Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is one of the most commonly mutated oncogenes. It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation. In this study, machine learning was applied to develop a QSAR(quantitative structure-activity relationship) model for KRAS small molecule inhibitors. A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system) for KRAS inhibitors were collected from three databases: ChEMBL, BindingDB, and PubChem. And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models, namely, random forest, support vector machine, and extreme gradient boosting machine. The results showed that the SVM model combined with mutual information feature selection exhibited the best performance: AUCtest=0.912, ACCtest=0.859, F1test=0.890. Moreover, it also demonstrated good predictive performance on the external validation set(AUCExt=0.944, RecallExt=0.856, FPRExt=0.111). This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

Influence of effective liver drainage volume on overall survival in patients with malignant hilar biliary obstruction: a multicenter study / 中华消化内镜杂志

Objective:To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction.Methods:Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence.Results:The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95% CI: 1.8-7.2) months, 5.6 (95% CI: 5.0-6.2) months and 6.6 (95% CI: 5.2-8.0) months. The overall survival time was 2.4 (95% CI: 1.8-3.0) months, 4.0 (95% CI: 3.4-4.6) months and 4.9 (95% CI:4.4-5.4) months, respectively. The clinical success rate ( χ 2=8.28, P=0.012), median stent patency period ( χ 2=18.87, P=0.015) and overall survival time ( χ 2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95% CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95% CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95% CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L ( HR=1.35, 95% CI:1.14-1.60, P<0.001),metal stents ( HR=0.67, 95% CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95% CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95% CI:0.41-0.81, P=0.002) and anti-tumor therapy ( HR=0.51, 95% CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion:When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.

Application value of different metal stents placement position in endoscopic drainage of malig-nant hilar bile duct obstruction: a multicenter study / 中华消化外科杂志

Objective:To investigate the application value of different metal stents place-ment position in endoscopic drainage of malignant hilar bile duct obstruction.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 300 patients with malignant hilar bile duct obstruction who were admitted to 3 medical centers, including 216 patients in the Third Affiliated Hospital of Naval Medical University, 48 patients in the Xijing Hospital of Air Force Medical University, 36 patients in the First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, from January 2012 to January 2019 were collected. There were 164 males and 136 females, aged (67±12)years. All patients were determined to be unresectable by multidisciplinary consultation and underwent endoscopic retrograde cholangiopancreatography. Observation indicators: (1) clinicopathological features of patients; (2) follow-up; (3) analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Follow-up was conducted using outpatient examination and telephone interview to detect patency of metal biliary stents and survival of patients up to July 2019 or death of patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. COX regression model was used for univariate and multivariate analyses. Factors with P<0.1 in univariate analysis were included in multivariate analysis. Results:(1) Clinicopathological features of patients. Of the 300 patients, 163 cases underwent endoscopic drainage with at least one metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as crossing papilla), and 137 cases underwent endoscopic drainage with no metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as no crossing papilla). Age, disease type (hilar cholangiocarcinoma, hepatocellular carcinoma, intrahepatic cholangio-carcinoma, gallbladder carcinoma, metastatic cholangiocarcinoma), metal biliary stents type (unilateral metal biliary stent, bilateral metal biliary stents) of patients with crossing papilla were (68±13)years, 95, 8, 11, 31, 18, 63, 100, respectively. The above indicators of patients with no crossing papilla were (64±12)years, 63, 22, 20, 23, 9, 126, 11, respectively. There were significant differences in the above indicators between patients with crossing papilla and patients with no crossing papilla ( t=2.70, χ2=17.69, 90.79, P<0.05). (2) Follow-up. All the 300 patients were followed up for 5.4(3.1,9.3)months. The patency time of metal biliary stents was 9.0(8.2,9.8)months and 6.4(4.8,8.0)months of patients with crossing papilla and patients with no crossing papilla, showing a significant difference between them ( χ2=8.23, P<0.05). The overall survival time was 5.5(4.2,6.8)months and 5.5(4.3,6.8)months of patients with crossing papilla and patients with no crossing papilla, showing no significant difference between them ( χ2=0.28, P>0.05). (3) Analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Results of univariate analysis showed that type of metal biliary stents and the placement position of metal biliary stents were related factors affecting the patency time of metal biliary stents [ hazard ratio( HR)=0.44, 0.60, 95% confidence intervals as 0.30?0.64, 0.42?0.85, P<0.05]. Results of multi-variate analysis showed that bilateral metal biliary stents was an independent protective factor for the patency time of metal biliary stents ( HR=0.46, 95% confidence interval as 0.29?0.72, P<0.05). Results of univariate analysis showed that disease type (intrahepatic cholangiocarcinoma versus hilar cholangiocarcinoma), preoperative serum total bilirubin, type of metal biliary stents, anti-tumor therapy were related factors affecting the overall survival time of patients ( HR=1.05, 1.43, 0.72, 0.61, 95% confidence intervals as 0.70?1.57, 1.12?1.83, 0.55?0.92, 0.47?0.81, P<0.05). Results of multi-variate analysis showed that age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L were independent risk factors for the overall survival time of patients ( HR=1.35, 1.98, 1.46, 95% confidence intervals as 1.02?1.79, 1.40?2.80, 1.13?1.89, P<0.05), and bilateral metal biliary stents, anti-tumor therapy were independent protective factors for the overall survival time of patients ( HR=0.68, 0.60, 95% confidence intervals as 0.53?0.89, 0.45?0.80, P<0.05). Conclusions:Endoscopic drainage with or without metal biliary stents' distal portion crossing the duodenal main papilla is safe and feasible for patients with malignant hilar bile duct obstruction. Bilateral metal biliary stents is an independent protective factor for the patency time of metal biliary stents. Age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L are independent risk factors for the overall survival time of patients, and bilateral metal biliary stents, anti-tumor therapy are independent protective factors for the overall survival time of patients.

Screening of key immune genes and pathways related to the ineffectiveness of interferon alpha treatment in patients with chronic hepatitis B based on GEO database / 西安交通大学学报(医学版)

【Objective】 To screen the differentially expressed immune genes between responders （Rs） and non-responders （NRs） in chronic hepatitis B patients receiving interferon alpha （IFN-α） treatment and to explore the molecular basis of IFN-α treatment failure. 【Methods】 The gene expression profile GSE27555 which contained 6 Rs and 7 NRs was obtained from the Gene Expression Omnibus （GEO） database； then differentially expressed genes between liver tissues of Rs and NRs were selected by the R software. The iconic immune gene set consisting of 1793 genes was downloaded from the immunology database and analysis portal （ImmPort）. The immune genes were extracted from the differentially expressed genes to obtain the differentially expressed immune genes. Subsequently， Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the differentially expressed immune genes were performed by the R software. Protein-protein interaction （PPI） network of the differentially expressed immune genes was constructed using the STRING online tool. The plugin CytoHubba of the Cytoscape software was applied to identify the top 10 genes by using Degree， MCC， MNC， and Closeness algorithms； then the intersection was taken to obtain the hub genes. 【Results】 A total of 88 differentially expressed immune genes， consisting of 13 upregulated and 75 downregulated genes， were identified between Rs and NRs. GO analysis showed that the differentially expressed immune genes were significantly enriched in T cell activation， cell chemotaxis， regulation of cell-cell adhesion， antigen processing and presentation. KEGG pathway analysis suggested that the differentially expressed immune genes were significantly enriched in cytokine-cytokine receptor interactions， Th cell differentiation， antigen processing and presentation， interactions between viral proteins and cytokines and cytokine receptors， chemokine signaling pathways， T cell receptor signaling pathway， IL-17 signaling pathway， natural killer cell-mediated cytotoxicity， Toll-like receptor signaling pathway， and other immune response signaling pathways. The top 7 hub genes， identified by the plugin cytoHubba of the Cytoscape software by using Degree， MCC， MNC and Closeness algorithms， were CD8A， IFNG， CCL2， CCL5， CXCL10， CCL4， and FCGR3A. 【Conclusion】 This study made a comprehensive analysis of the differentially expressed immune genes and signal pathways between Rs and NRs by bioinformatics， and identified 7 Hub genes related to the ineffectiveness of IFN-α treatment in CHB patients. These hub genes may serve as potential biomarkers for predicting the response of IFN-α treatment in CHB patients.

Identification of Armeniacae Semen Amarum Adulterated in Persicae Semen by Allele-specific Polymerase Chain Reaction / 中国实验方剂学杂志

Objective:Due to the limitation of traditional identification methods of Chinese medicinal materials， the study established a rapid method to identify Persicae Semen mixed with Armeniacae Semen Amarum by allele-specific polymerase chain reaction （PCR）. Method:By comparing the ribosomal DNA internal transcribed spacer （ITS） gene sequences of Persicae Semen and Armeniacae Semen Amarum， single nucleotide polymorphism （SNP） sites were searched and specific primers were designed. Different Persicae Semen and Armeniacae Semen Amarum samples were amplified by PCR， the effects of annealing temperature， primer concentration and cycle number on the PCR reaction system were optimized， and the specificity and detection limit of this method were investigated. In addition， the established PCR method was used to detect the samples of Persicae Semen mixed with different proportion of Armeniacae Semen Amarum from different sources and producing areas. Result:A specific PCR method for identifying Persicae Semen mixed with Armeniacae Semen Amarum was established. When the annealing temperature was 63 ℃ and the number of primer cycles was 30， only Armeniacae Semen Amarum could be amplified with 432 bp specific band， while Persicae Semen samples did not have this band. The minimum detection limit of this method for Armeniacae Semen Amarum was 0.2 ng， and the detection limit for Armeniacae Semen Amarum adulterated in Persicae Semen was 1%. Conclusion:The established allele-specific PCR method can accurately detect whether there is Armeniacae Semen Amarum in Persicae Semen， which can provide experimental basis for the quality control of Persicae Semen and guarantee the safety of its clinical use.

New mutation site c.361C > T of RS1 gene in X-linked retinoschisis / 中华眼底病杂志

Objective:To study the characteristics of the genotype and phenotypic in a family with X-linked retinoschisis (XLRS) due to RS1 mutation. Methods:A retrospective clinical study. An XLRS family of 4 generations of 26 people were included in the study. Among them, 8 participants were males and 7 participants were females. Routine ophthalmologic examination was performed on 3 patients in the family including the proband and 12 patients with normal phenotype. Optical coherence tomography was performed in 2 of the 3 patients. Peripheral venous blood was extracted from all participants, whole-genome DNA was extracted, and potential pathogenic genes were screened by Panel sequencing. Conservative analysis, pathogenicity analysis and protein structure prediction were carried out by software tools. The pathogenicity of gene mutations was analyzed according to the American Society of Medical Genetics and Genomics (ACMG) guidelines.Results:The proband was 3 years old. Optical coherence tomography (OCT) examination showed that the retinal core layer in the macular area of both eyes had a cystic change, which was segmented by vertical or oblique bridging tissue. The proband's uncle was 32 years old. OCT examination showed atrophy in the macular area of the left eye. The macular area of the right eye was cystoid, segmented by vertical or oblique bridging tissue. No abnormality was found in the fundus examination of the proband's parents and 10 members of his family. Panel sequencing showed that c.361C>T/ p.Q121X hemizygous mutation was found in the fifth exon of RS1 gene in the proband (Ⅳ3) and 2 patients (Ⅱ1, Ⅲ8). The mother was a heterozygous mutation carrier of the gene, while the father had no mutation. The mutant gene causes premature termination of RS1, a truncated protein encoding 224 amino acids to 120 amino acids. Of the 10 patients with normal fundus examination, 6 participants were normal. The mutation was carried by four people, which were women. Homology analysis of the protein sequence showed that the mutant site was highly conserved in 12 mammals. Three-dimensional structural analysis of RS1 protein showed that the c-terminal amino acid sequence of the mutant protein was more than 50% missing. Analysis of ACMG guidelines indicated that the mutation was pathogenic. Conclusion:The RS1 mutation site c.361C>T/p.Q121X is a new mutation site of XLRS.

Clinical diagnosis and treatment and prognosis of appendiceal neoplasms / 中华普通外科杂志

Objective:To analyze the pathogenesis and clinical characteristics of appendiceal neoplasms and its prognosis.Methods:In recent 14 years, 94 appendiceal neoplasms were found among 6 334 patients undergoing appendectomy in a single center of Ordos Central Hospital.The initial symptoms, clinical features, auxiliary examinations, pathology, surgical methods, and clinical outcomes of 94 patients diagnosed with appendix tumors were recorded.Results:Appendiceal neoplasms accounted for 1.48% for all undergoing appendectomy. Among these 94 cases, 49 cases were female and 45 cases were male. The median age was 59.5 years. 80 cases were followed up with a follow-up rate of 85.1%, and the follow-up period was 2-175 months.The 5-year overall survival rate was 91.9% and the 10-year overall survival rate was 88.9%.The results of univariate analysis of prognosis showed that the prognosis of patients with WBC count>10.0×10 9/L (χ 2 =8.884, P=0.003) and lymph node metastasis(χ 2 =17.216, P=0.001) was relatively poor. The prognosis of appendiceal adenocarcinoma is relatively poor compared with mucinous tumors(χ 2=13.857 , P=0.001 ). Conclusions:The incidence of appendiceal neoplasms is very low; Chronic lower right abdominal pain accounted for a large proportion of the manifestations; Classification of appendiceal neoplasms, leukocyte count and lymph node metastasis predict the prognosis of patients with appendiceal neoplasms.

Status of glycosylated hemoglobin and prediction of glycemic control among patients with insulin-treated type 2 diabetes in North China: a multicenter observational study / 中华医学杂志(英文版)

BACKGROUND@#Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control.@*METHODS@#Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models.@*RESULTS@#The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively).@*CONCLUSIONS@#More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease.@*METHODS@#The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes＜5×10/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized.@*RESULTS@#The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×10/L, the levels of LDH and β2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin.@*CONCLUSIONS@#The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.

Timeless promotes the proliferation of hepatocellular carcinoma cell by reprogramming of glucose metabolism / 中华肿瘤杂志

Objective@#To explore the function and molecular mechanism of Timeless in promoting hepatocellular carcinoma (HCC) growth.@*Methods@#The expression of Timeless in HCC and paracancer tissues were analyzed by using the public data of HCC. Timeless was overexpressed in MHCC97L cells and silenced in MHCC97H cells, respectively, and the expression of Timeless and its downstream molecules were detected by real-time PCR and western blot. The effects of Timeless on cell glycolysis, oxidative phosphorylation and proliferation were detected by the glucose uptake experiment, lactic acid detection experiment, the extracellular fluid pH detection experiment, cell oxygen consumption test and cell viability assay, respectively.@*Results@#The level of Timeless in HCC tissue was significantly higher than that of paracancer tissue (P<0.05). The relative cellular glucose uptake levels in the groups of Timeless knockdown, including siTimeless-1 and siTimeless-2 group were 0.510±0.119 and 0.508±0.099, respectively, significantly different from that of control group (P<0.05); The relative cellular uptake level of Timeless overexpressed group was 1.953±0.324, significantly different from that of vector transfected group (P<0.05). The relative levels of lactic acid production in the siTimeless-1 and siTimeless-2 group were 0.579±0.096 and 0.550±0.120, respectively, significantly different from that of control group (P<0.05); The relative production level of lactic acid in the Timeless overexpressed group was 1.463±0.179, significantly different that of vector transfected group (P<0.05). The extracellular pH values of siTimeless-1 and siTimeless-2 group were 7.390±0.035 and 7.370±0.060, respectively, significantly different from that of control group (P<0.05); the extracellular pH value of Timeless overexpressed group was 7.130±0.031, significantly different than vector transfected group (P<0.05). Oxygen consumption rate of siTimeless-1 and siTimeless-2 group were 3.686±0.389 and 3.955±0.431, respectively, significantly higher than 1.690±0.297 of control group (P<0.05); Oxygen consumption rate of Timeless overexpressed group was 1.302±0.336, significantly lower than 3.185±0.262 of vector transfected group (P<0.05) Timeless inhibited the expression of p53. The cell glucose uptake, lactic acid production, the pH of extracellular culture medium and cell oxygen consumption of control group were not significantly different from that of Timeless and p53 co-silenced group [(si-Timeless+sip53) group] (P>0.05); the glucose uptake, the production of lactic acid, the pH of the extracellular culture medium and the oxygen consumption of Timeless co-transfected with p53 (Timeless+p53) group were not significantly different from those of vector transfected group (P>0.05). Timeless promoted the proliferation of HCC cells through inhibiting the expression of p53.@*Conclusion@#Timeless promotes reprogramming of glucose metabolism and proliferation of HCC cells by inhibiting the p53-dependent signaling pathway.

Effect of intrahippocampal injection of anti-cellular prion protein monoclonal antibody on cognitive deficits in APPswe/PSEN1 transgenic mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of intrahippocampal injection of cellular prion protein (PrP) antibody on cognitive deficits of APPswe/PSEN1 transgenic mice.</p><p><b>METHODS</b>Eight-month-old male APPswe/PSEN1 transgenic mice were subjected to bilateral intrahippocampal injection of a single dose (2 µL) of anti-PrP monoclonal antibody (EP1802Y) or PBS, with wild-type C57Bl/6J mice serving as the control group. After two months, the mice were tested for cognitive behaviors using open filed (OF) test, Morris water maze (MWM) test, fear conditioning (FC) test, and novel object recognition (NOR) test, and immunohistochemistry was used to examine the changes in hippocampal expression of Aβ.</p><p><b>RESULTS</b>The EP1802Y-treated and PBS-treated mice showed no significantly differences in the performance in OF test in terms of central activity time or total distance of activity (P>0.05), nor in NOR test in terms of novel object recognition index (P>0.05). In MWM test, the EP1802Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice (P<0.05), but EP1802Y-treated mice had a significantly shorter swimming distance to find the platform than PBS-treated mice (P<0.05). No significant differences were found in the results of FC test among the 3 groups. Immunohistochemistry revealed a significantly reduced expression of Aβ in the hippocampus of EP1802Y-treated mice.</p><p><b>CONCLUSION</b>Intrahippocampal injection of PrP antibody can improve cognitive deficits of APPswe/PSEN1 transgenic mice, which sheds light on a novel therapeutic approach for Alzheimer's disease that targets PrP to lower the toxicity of Aβ oligomer.</p>

Analysis of Clinical Characteristics for 24 Cases of Nodal Marginal Zone Lymphoma / 中国医学科学院学报

Objective To summarize and investigate the characteristics of nodal marginal zone lymphoma (NMZL). <strong>Method</strong> The clinical data and laboratory characteristics of of NMZL patients admitted in our hospital between January 2002 and September 2013 were analyzed retrospectively. <strong>Results</strong> Twenty-four patients were enrolled in the study. The median age was 54.4 (28-70) years,and the male/female ratio was 1:1. Most of the patients (95%) had bone marrow involvement,40.9% (9/22) had elevated lactate dehydrogenase level,8.3% (2/24) had the positive expression of hepatitis C virus antibody,33.3% (6/18) had positive autoimmune antibodies,and 33.3% (8/24) had monoclonal immunoglobulins in the serum. All of the patients expressed CD19 and CD20 cell markers,whereas none of them expressed CD10 cell marker. The positive rate of CD5 marker was 10% (1/10),the positive rate of CD23 marker was 50% (5/10),whereas no patient had the expressions of both CD5 and CD23 at the same time. The total overall remission rate was 81.25%,and the total complete remission rate was 56.2%. The separate overall remission and complete remission rate had increasing trends in rituximab subgroup than subgroups without using rituximab(P=0.136,P=0.262).<strong>Conclusion</strong> NMZL has a low incidence and can be seen in both males and females. It often invades bone marrow. Rituximab may increase the response rate and even improve the progression free survival.

Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia / 中国医学科学院学报

Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were significantly higher than those treated without rituximab (38.9% vs. 21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9) months,and the median PFS and OS for patients treated without rituximab were 28.0 (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically significant (P=0.094,P=0.109). According to the cytogenetic features,patients were further divided into high-risk subgroup (with chromosome 17p deletion or 11q deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of patients treated with rituximab was 86.4%,which was significantly higher than that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk subgroup,the PFS was marginally prolonged in patients treated with rituximab,but the difference was not statistically significant(P=0.050). Conclusions Compared with traditional chemotherapy,the chemoimmunotherapies with rituximab result in higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q deletion,the use of rituximab can marginally prolong PFS.

Endoscopic retrograde catheterization of gallbladder and transpapillary gallbladder stenting for gallbladder diseases / 中华消化内镜杂志

Objective To evaluate the technical feasibility and safety of endoscopic retrograde catheterization of gallbladder (ERCG) and endoscopic transpapillary gallbladder stenting (ETGS) for gallbladder diseases.Methods Patients who underwent ERCG and ETGS in Eastern Hepatobiliary Hospital from January 2010 to June 2016 were enrolled to this retrospective study.The superselection time of cystic duct,the catheterization time of gallbladder,postoperative symptoms and complications were analyzed.Results A total of 10 patients were enrolled to this study,including 2 cases of acute calculous cholecystitis,4 cases of percutaneous transhepatic gallbladder drainage (PTGBD) and 4 cases of cholecystocholedocholithiasis.The success rates of ERCG and ETGS were 100％.Symptoms were relieved in all patients and PTGBD catheter was removed after ETGS.The mean times of ERCG and ETGS were 10.2 ± 6.9 min and 17.0 ± 8.0 min respectively.The mean times of ERCG were 18.5±4.9 min,13.0±3.6 min and 3.3± 1.3 min,respectively (F=18.86,P =0.002).The mean times of ETGS were 25.5±4.9 min,21.0± 4.7 min and 8.8 ± 1.0 min,respectively (F =18.04,P =0.002).Complications included 1 case of cholangitis and 1 case of hyperamylasemia.Cholangitis was relieved after anti-inflammatory treatment.No acute pancreatitis,bleeding,perforation or procedure-related death occurred.Conclusion ERCG and ETGS are safe and feasible,which can play important roles in the treatment of specific gallbladder diseases or gallbladder with bile duct diseases.

Expression and clinical analysis of snail in 41 patients with non small cell lung cancer / 实用医学杂志

Objective To study the expressions of snail mRNA and protein in human non-small cell lung cancer (NSCLC) and their correlations to patient clinical features.Methods Real-time fluores-cence quantitative PCR (qRT-PCR) and immunohistochemical were used to analyze the expressions of snail in a total of 41 pairs of NSCLC tissues,12 specimens of normal lung tissues.Results The expressions of snail mRNA in NSCLC tissues were significantly higher than the corresponding adjacent tissues (P ＜ 0.01).The expression rate of snail protein of NSCLC tissues (25/41) were significantly higher than that in adjacent tissues (2/41,P ＜ 0.01).There was no snail expression in non-cancerous lung tissues.The level of mRNA and protein in snail was associated with lymph node metastasis and clinical stage of non-small cell lung cancer (P ＜ 0.05).Conclusion The higher expression of snail may promote the metastasis of lung cancer.The expressions of snail are related to the development of human non-small cell lung cancer.

Divergence Analysis of Hepatitis Virus Infection between Aggressive and Indolent B Cell Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence rate of hepatitis B virus(HBV)and hepatitis C virus(HCV)between aggressive and indolent B cell non-Hodgkin's lymphoma (B-NHL), and to compare the different infection rate of Hepatifis Virus between the 2 groups.</p><p><b>METHODS</b>Integrated clinical information of 733 newly diagnosed indolent B-NHL patients and 148 aggressive B-NHL patients from January 1994 to January 2014 was retrospectively analyzed. The difference of hepatitis virus infection was compared between the 2 groups.</p><p><b>RESULTS</b>The positive rate of HCV-Ab was 1.8% in 881 newly diagnosed B-NHL patients. The HCV prevalence was 1.9% and 1.35% in the indolent and aggressive B-NHL group respecitvely. Compared with general population, the HCV positive rate was significantly higher in the whole B-NHL group and the indolent group(1.8% vs 0.4%,1.9% vs 1.4%)(P<0.01), while it was not significantly different in the aggressive group (1.35% vs 0.4%)(P=0.068). The positive rate of HCV-Ab was not significantly different between the indolent and the aggressive group (1.9% vs 1.35%)(P=0.639). The HBs-Ag positive rate in the whole B-NHL group was 9.0%, which was significantly higher than that in the general population (9.0% vs 7.2%)(P<0.05). The positive rate of HBs-Ag in the indolent and aggressive B-NHL group was 7.9% and 14.2%, respectively. It was significantly higher in the aggressive group than that in the indolent one (14.2% vs 7.2%)(P<0.01). Compared with the general population, the aggressive group had significantly higher prevalence rate of HBV. However, it was not significantly different between the indolent group and the general population (7.9% vs 7.2%)(P>0.05).In the aggressive B-NHL group,the co-expression of HBs-Ag,HBe-Ag and anti-HBc-Ab was 4.4%, which was higher than that in the indolent one (4.7% vs 1.2%)(P<0.01). However, compared with the indolent group, the co-expression of HBs-Ag, anti-HBe-Ab and anti-HBc-Ab was not significantly different in the aggressive group (5.5% vs 6.1%)(P>0.05).</p><p><b>CONCLUSION</b>The HCV is more relevant with indolent B-NHL, the HBV has more relevance with the aggressive patients.</p>

Endoscopic closure for acute colonic perforations with novel successive endoclips in animal model / 中华消化内镜杂志

Objective To evaluate the feasibility and the safety of endoscopic closure for acute colon perforations with novel successive endoclips in animal model. Methods Approximately 1. 5 to 2 cm colonic full-thickness resections were created with an electrotome in 3 Ba-Ma pigs that were under general anesthesia and were closed with the conventional endoclips and novel successive endoclips respectively. The procedure time and the efficacy of each endoclip were recorded. After the procedure,the general condition and physiological indicators were carefully monitored. After a follow-up of 1 week,the pigs were euthanized for an endoscopic observation of the healing condition and the residual endoclips. A postmortem examination was performed to observe the abdominal infection and incision condition. Transverse sections of the colon across the site of perforation were taken for histopathologic examination to assess the healing process. Results All the colonic perforation models in three pigs were established successfully. Endoscopic closure for acute colon perforation with two kinds of endoclips was technically successful in all 3 pigs. The mean time of the procedure with successive endoclip was less than that with the conventional endoclip(54. 0 seconds VS 91. 9 seconds,P<0. 001),but the successful release rate of the successive endoclip was lower than that of the conventional endoclip without significant difference[62. 5%(15/ 24)VS 14/ 16,P= 0. 17].All the ani-mals survived without infection and hemorrhage. Five perforations demonstrated signs of healing,whereas one closed with the novel successive endoclips failed to heal completely. Conclusion Endoscopic closure for a-cute colon perforations with novel successive endoclips is effective and safe. The novel successive endoclip has the advantage of saving time,but it needs to be further improved and perfected to satisfy the clinical need.

Advances in genome-wide association studies of sporadic Alzheimer′s disease / 国际药学研究杂志

Alzheimer′s disease(AD)is a neurodegenerative disorder resulted from complicate interactions between genes and environment. There is no effective therapy so far. The genome-wide association study(GWAS)provides the opportunity to discover the risk genes of sporadic AD,which is informative for revealing the pathogenesis of AD and guiding new drug development. In this re?view,we summarize the current findings of genetic studies of AD,the risk genes and their biological relevance with AD,and new drug development strategy supported by genetic studies.

Advances in genome-wide association studies of sporadic Alzheimer’s disease / 国际药学研究杂志

Alzheimer’s disease AD is a neurodegenerative disorder resulted from complicate interactions between genes and environment. There is no effective therapy so far. The genome-wide association study GWAS provides the opportunity to discover the risk genes of sporadic AD, which is informative for revealing the pathogenesis of AD and guiding new drug development. In this review, we summarize the current findings of genetic studies of AD, the risk genes and their biological relevance with AD, and new drug development strategy supported by genetic studies.