Establishment and validation of a nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Objective: To establish a novel nomogram to predict overall survival of patients with gastric neuroendocrine neoplasms (g-NEN). Methods: A case control study was conducted. Clinicopathological and follow-up data of patients with g-NEN who were treated in two academic medical centers in Southern China between July 2008 and June 2018 were retrospectively collected, including 174 patients from Sun Yat-sen University Cancer Center and 102 patients from the First Affiliated Hospital of Sun Yat-sen University. Univariate survival analysis using Kaplan-Meier method and multivariate analysis using Cox regression were performed to identify prognostic factors. A nomogram was subsequently established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility. Results: A total of 276 patients were enrolled in the study, of whom 189 patients were male and 87 were female. The age at diagnosis was below 60 years old in 150 patients and 60 years or older in 126 patients. There were patients diagnosed with gastric neuroendocrine carcinoma (g-NEC) and 101 patients with gastric neuroendocrine tumor (g-NET). The number of patients with primary tumor locating at upper, middle and lower parts of stomach was 131, 98 and 47, respectively. As for TNM stage, 72 patients were categorized as stage I, 26 patients stage II, 93 patients stage III, and 85 patients stage IV. Univariate analysis indicated that age, pathological type, primary site, Ki-67 index, T stage, N stage, and M stage were associated with overall survival of g-NEN patients (all P<0.05). Multivariate regression analysis testified that high Ki-67 index, advanced T stage and advanced M stage were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.806 (95%CI: 0.769-0.863). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in g-NEN patients. The ROC curves and DCA showed that the nomogram had better differentiation and clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system (the area under the ROC curve was 0.862 vs. 0.792). Conclusion: The first nomogram to predict overall survival of patients with g-NEN is established and verified in this study, which provides individual prediction of 3-year overall survival rate and is applicable to both g-NET and g-NEC patients.

Epidemiological characteristics of severe fever with thrombocytopenia syndrome and its inapparent infection in Tiantai County, Zhejiang Province / 中国人兽共患病学报

We investigated the characteristics and epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) infection in Tiantai County,Zhejiang Province.Active surveillance and epidemiological investigation were employed with the serum samples collected simultaneously.The samples were detected by fluorescence quantitative PCR assay recommended by national standard of China.By descriptive epidemiology,the SFTS cases in 2012-2015 in Tiantai and related data were analyzed.In 2012-2015,there were 12 new cases of SFTS infection and 2 deaths,including 5 males and 7 females (39 to 75 yrs).The peak incidence was found from April to August.The main clinical manifestations was fever (100 ％),chills and fatigue (83％),and body pain (75％).The positive rate of nucleic acid screened in subclinical population was 1.4％;8 ca ses with definite records of tick bites (67 ％).In conclusion,several cases of SFTS have been confirmed in Tiantai County with two inapparent infections,which suggest the urgency and importance to strengthen the active surveillance,prevention and control measures and health education s in the coming days.

Epidemiological characteristics of severe fever with thrombocytopenia syndrome and its inapparent infection in Tiantai County, Zhejiang Province / 中国人兽共患病学报

We investigated the characteristics and epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) infection in Tiantai County,Zhejiang Province.Active surveillance and epidemiological investigation were employed with the serum samples collected simultaneously.The samples were detected by fluorescence quantitative PCR assay recommended by national standard of China.By descriptive epidemiology,the SFTS cases in 2012-2015 in Tiantai and related data were analyzed.In 2012-2015,there were 12 new cases of SFTS infection and 2 deaths,including 5 males and 7 females (39 to 75 yrs).The peak incidence was found from April to August.The main clinical manifestations was fever (100 ％),chills and fatigue (83％),and body pain (75％).The positive rate of nucleic acid screened in subclinical population was 1.4％;8 ca ses with definite records of tick bites (67 ％).In conclusion,several cases of SFTS have been confirmed in Tiantai County with two inapparent infections,which suggest the urgency and importance to strengthen the active surveillance,prevention and control measures and health education s in the coming days.

Anticancer effects of crude extract from Melia toosendan Sieb. et Zucc on hepatocellular carcinoma in vitro and in vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo.</p><p><b>METHODS</b>Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography (HPLC). Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract.</p><p><b>RESULTS</b>HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50, 72 h) was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/(kg d)] and low-dose [0.138 mg/(kg d)] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced.</p><p><b>CONCLUSIONS</b>Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.</p>

Randomized phase II trial on escalated doses of Rh-endostatin (YH-16) for advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the response rate (RR), time to tumor progression (TTP), quality of life (QOL) and adverse reaction in the treatment of pretreated advanced non-small cell lung cancer (NSCLC) using escalated doses of rh-endostatin (YH-16), and to determine the optimal dose for clinical application.</p><p><b>METHODS</b>In this phase II randomized, controlled, multicenter trial, the patients were randomly divided into two groups to receive daily 3 hours intravenous infusion of either 7.5 mg x m(-2) or 15 mg/m(2) YH-16 for 28 days.</p><p><b>RESULTS</b>Totally, 68 patients were entered and 60 patients were evaluable. There were no differences in RR (3.0% in both groups, P > 0.05), median TTP (ITT: 60 days versus 71 days, P > 0.05), QOL and incidence rate of adverse reactions (48.6% versus 38.7%, P > 0.05). No significant unexpected adverse events were observed.</p><p><b>CONCLUSION</b>Rh-endostatin may have anti-tumor activity with high clinical benefit rate and is well tolerated in pretreated advanced NSCLC patients. The dose of 7.5 mg x (m(2))(-1) x d(-1) is clinically recommended.</p>

Expression of soluble GM-CSF-Ralpha in patients with acute myeloid leukemia / 中国实验血液学杂志

To evaluate soluble GM-CSF-Ralpha expression in patients with acute myeloid leukemia (AML) and its clinic significance, plasma concentration of solGM-Ralpha in de novo 66 patients with AML was detected by enzyme-linked immuno-sorbent assay, and the relationship between solGM-Ralpha levels and various clinical parameters was analyzed. The result showed that the levels of solGM-Ralpha in plasma of patients with AML were significantly higher than that in plasma of normal controls; the lowest level of solGM-Ralpha was found in plasma of patients with AML-M3 (3897.75 +/- 2651.43 pg/ml), the highest level of solGM-Ralpha was observed in plasma of patients with AML-M5 (9990.92 +/- 6325.43 pg/ml). Patients with high level of solGM-Ralpha were generally accompanied with a distinct clinical picture, including higher counts of white blood cell and myeloid precursors, as well as higher expression of CD34, CD95 and CD116 antigen. It is concluded that the high level of solGM-Ralpha in plasma of patients may suggest AML poor prognosis and play a role in pathogenesis of leukemia, the GM-CSF and its receptor solGM-Ralpha needs further study.

A transgenic mouse that targets the expression of Cre recombinase in hepatocyte / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct a mouse that specifically expresses Cre recombinase in hepatocyte.</p><p><b>METHODS</b>A hepatocyte specific transgenic construct containing mouse albumin promoter, the Cre recombinase gene and the poly (A) of human growth factor gene was generated. The linearized constructs were introduced into the fertilized eggs by microinjection to obtain the transgenic mice. The transcriptional specificity of Cre recombinase was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression and function of Cre recombinase were detected by PCR and Southern Blot after crossing the Alb-Cre transgenic mice with the Smad4 conditional knockout mice.</p><p><b>RESULTS</b>The linearized constructs were microinjected into 837 fertilized eggs, and then the 797 effective eggs of microinjected eggs were implanted into the oviducts of 27 pseudo pregnant mice. In the 53 offspring, there were 6 mice carrying the transgene identified by polymerase chain reaction (PCR) and Southern Blot. Cre recombinase transcripts were detected in the livers and testis of the Alb-Cre transgenic mice using RT-PCR. The Cre recombinase was expressed in the livers of the double heterozygous for Alb-Cre and Smad4 floxed allele, and the exon 8 floxed by loxP site was deleted.</p><p><b>CONCLUSION</b>A hepatocyte-specific Cre transgenic mouse was generated successfully. The Cre recombinase expressed specifically in liver and could mediate the recombination between loxP sites in vivo.</p>

Progresses in mouse chromosome engineering / 生物工程学报

Mouse chromosome engineering, characterized by deletion and rearrangement of large fragment of chromosome, has been an important method for studying the function of mouse genome on a large scale. The latest progress in mouse chromosome engineering was introduced.