Effect of HIF-1α on Angiogenesis-Related Factors in K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the mechanisms of angiogenesis in chronic myeloid leukemia (CML) through detecting the levels of angiogenesis-related factors secreted from K562 cells after overexpression and interference of HIF-1α gene in K562 cells.@*METHODS@#The K562 cells were transfected by lentiviruses carried and interfered HIF-1α gene, then the transtected K562 cells with carried and interfered with HIF-1α gene were enrolled in overexpression and interference groups respectively, at the same time the K562 cells transfected by the empty virus were enrolled in control group. The cells were harvested after culture for 72 hours under normoxid condition. The transfection efficient in 3 groups was detected by fluorescence microscopy; the mRNA expression of HIF-1α gene and angiogenesis-related factors was detected by RT-PCR; the concentration of angiogenesis-related factors in the caltured supernatant was detected by ELISA.@*RESULTS@#The optimal MOI of K562 cells transfected with lentivirus was 10 and the transfection efficiency was about 50%. The positive rate of transfection after screening by puromycin was more than 90%. The mRNA expression of ANG-I, ANG-II, TGF-α and VEGF in the interference group was lower than that in the over-expression group, and the TGF-β1 mRNA expression in the interference group was higher than in the over-expression group. The mRNA expression of ANG-I and VEGF in the interference group was lower than that in the control group. TGF-αdid not could be detected, and the culture supernatant concentration of ANG-I and TNF-α in the interference group was lower than in the over-expression group, while the VEGF concentration in the interference group was higher than that in the over-expression group. All of the above-mentioned differences were statistically significant (P＜0.05).@*CONCLUSION@#The positive K562 cells transfected with leutivirus have been harvested by screening with puromycin. The HIF-1α mRNA positively regulates the mRNA expression of ANG-1, ANG-2, TGF-α, VEGF in K562 cells, promotes the antocrine ability of ANG-1 and TNF-α, moreover not stimulates the autocrine of TGF-α, the up-regulation of HIF-1α expression can inhibit the expression TGF-β1 in K562 cells and the autocrine of TGF-β1.

Expression of SHIP 1 in the Patients with Acute Myeloid Leukemia and Its Influence on the Apoptosis of Human Leukemia Cells / 现代生物医学进展

Objective:To investigate the expression of SHIP1 in the patients with acute myeloid leukemia and its effect on the apoptosis of human leukemia cells.Methods:The expression of SHIP1 in the bone marrow of patients with acute myeloid leukemia was detected by Westem blot.U937 cells was transfected with SHIP1 expression vector (pEGFP-SHIP1 group) and empty vector control (pEGFP group) respectively,U937 cells without transfection were used as the control group.Flow cytometry was used to detect the apoptosis of the cells,the expression of SHIP1,Bcl-2,Bax,Akt,p-Akt were detected by western blot.Results:The expression of SHIP1 in the bone marrow of patients with acute myeloid leukemia was significantly lower than that of the normal human bone marrow SHIP 1 (P＜0.01).The SHIP1 and Bax expressions as well as the apoptotic rate ofpEGFP-SHIP1 group were significantly higher than those of the control group(P＜0.01),while the Bcl-2 and p-Akt expressions were significantly lower than those in the control group(P＜0.01).Conclusions:SH-P1 expression was down regulated in the bone marrow of patients with acute myeloid leukemia.SHIP1 could promote the apoptosis of human leukemia cells via Akt signaling pathway.

Research progress on Chinese materia medica in treatment of intrahepatic cholestasis based on FXR-mediated regulation / 中草药

Intrahepatic cholestasis is a common disease and the formation mechanisms of this disease are complex. Until now, only two drugs (ursodeoxycholic acid and obeticholic acid) were approved by FDA for the treatment of cholestasis. Farnesoid X receptor (FXR) in cholestasis is an intriguing approach since this receptor is critically involved in the regulation of bile acid homeostasis. FXR serves as a sensor for bile acid and promotes enterohepatic clearance of bile acid by controlling the expression of genes involved in their transport and metabolism. Chinese materia medica (CMM) gained a significant effect in the treatment of intrahepatic cholestasis through multi-target, multi-channel effects, which aimed at major pathogenesis and secondary pathogenesis. Recently, a variety of CMM have been proved to activate FXR targets for the treatment of cholestasis, which has attracted widespread attention at home and abroad. In this paper, we reviewed the metabolism of bile acid, the potential of pharmacological modulators of FXR as novel therapies for cholestatic disorders, and summarized CMM for the treatment of cholestasis based on FXR targets. This paper may provide some theoretical guidance for the development of new drugs and CMM.

Early diagnosis and surgery timing of strangulated intestinal obstruction / 局解手术学杂志

Objective To investigate the early diagnosis and surgery timing of strangulated intestinal obstruction.Methods The clinical data of 90 patients with strangulated intestinal obstruction who were admitted into our hospital from January 2013 and January 2016 were retrospectively analyzed.And these patients were divided into the early stage group (28 cases) and the later stage group (62 cases).The rate of mortality and the rate of necrotic bowel resection of the two groups were analyzed.Results Among the 90 patients underwent emergency surgery,there were 88 cases cured and 2 cases died,and there were 10 cases (11.11％) of necrotic bowel resection among the survivor.In the early stage group,there were 8 cases of necrotic bowel resection and 1 case of death.In the later stage group,there were 2 cases of necrotic bowel resection and 1 case of death.Conclusion Early diagnosis and prompt surgical treatment can reduce the mortality of strangulation obstruction and necrosis of bowel resection.

Differential proteomic analysis of liver tissues between male and female C57BL / 6J mice by 2D-DIGE / 中国比较医学杂志

Objective To identify the differential proteomic expressions between the liver tissues of male and female mice, and investigate the mechanisms underlying gender differences in liver diseases. Methods Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF-MS) were used to identify the differentially expressed proteins in the liver tissues of male and female C57BL/6J mice. The differentially expressed proteins were validated by Western blot and further analyzed by bioinformatics, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Among the auto-detected 1767 protein spots by 2D-DIGE, 325 protein spots were differentially expressed (|ratio|≥1. 5, P< 0. 05) between the liver tissues of male and female mice, in which 78 spots were randomly selected for MALDI-TOF-MS identification and finally 48 distinct proteins were obtained. Compared with females, 14 and 34 proteins were up-or down-regulated in males, respectively. Among them, 6 differentially expressed proteins were validated by Western blot which confirmed the reliability of 2D-DIGE results. GO analysis showed that the differentially expressed proteins in the liver tissues of male and female mice are associated to various cellular component, molecular function and biological process. 6 pathways were significantly different between the liver tissues of males and females depending on KEGG analysis. Conclusions The proteomic data and related analysis of the liver tissues of C57BL/6J mice offer crucial clues for elucidating the underlying mechanisms of different gender effects on liver diseases.

Differential proteomic analysis of liver tissues between male and female C57BL / 6J mice by 2D-DIGE / 中国比较医学杂志

Objective To identify the differential proteomic expressions between the liver tissues of male and female mice, and investigate the mechanisms underlying gender differences in liver diseases. Methods Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF-MS) were used to identify the differentially expressed proteins in the liver tissues of male and female C57BL/6J mice. The differentially expressed proteins were validated by Western blot and further analyzed by bioinformatics, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Among the auto-detected 1767 protein spots by 2D-DIGE, 325 protein spots were differentially expressed (|ratio|≥1. 5, P< 0. 05) between the liver tissues of male and female mice, in which 78 spots were randomly selected for MALDI-TOF-MS identification and finally 48 distinct proteins were obtained. Compared with females, 14 and 34 proteins were up-or down-regulated in males, respectively. Among them, 6 differentially expressed proteins were validated by Western blot which confirmed the reliability of 2D-DIGE results. GO analysis showed that the differentially expressed proteins in the liver tissues of male and female mice are associated to various cellular component, molecular function and biological process. 6 pathways were significantly different between the liver tissues of males and females depending on KEGG analysis. Conclusions The proteomic data and related analysis of the liver tissues of C57BL/6J mice offer crucial clues for elucidating the underlying mechanisms of different gender effects on liver diseases.

Tyrosine kinase inhibitors for the intervention of major morbid events in myeloproliferative neoplasms：reports from the 57th American Society of Hematology annual meeting / 白血病·淋巴瘤

With the research progress of pathogenesis of JAK gene in myeloproliferative neoplasms (MPN), more tyrosine kinase inhibitors were developed. MPN quantify scoring system is used to determine the efficacy of tyrosine kinase inhibitors for MPN. The choice of tyrosine kinase inhibitors, tyrosine kinase for the relief of MPN symptom burden, etc, become the topics of the 57th American Society of Hematology (ASH) annual meeting.

Total Flavonoids from Flowers of Abelmoschus manihot for Amelioration of α-naphthylisothiocyanate-induced Cholestasis by Regulating Expression of Transporters / 中草药·英文版

Objective: To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot (TFA) against α-naphthylisothiocyanate (ANIT)-induced cholestasis. Methods: The hepatoprotective activities of TFA (125, 250 and 500 mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic mRNA and protein levels of transports, multidrug resistance-associated protein 2 (MRP2), bile salt export pump (BSEP), and Na+-taurocholate cotransporting polypeptide (NTCP) were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results: Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and mRNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion: TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.

Renal protective effects of superfine powder of rhodiola rosea on diabetic nephropathy in rats / 国际中医中药杂志

Objective To study the renal protective effects of superfine powder of Rhodiola rosea in diabetic nephropathy (DN)rats.Methods The DN rats model was established by one side nephrectomy and intraperitoneal injection of streptozotocin(STZ).Then rats were randomly divided into 6 groups:sham-operation group,model group,Rhodiola rosea common powder groups(3 g/kg·d-1),and superfine powder of low,medium and high dose groups (0.75、1.5、3.0 g/kg·d 1),10 rats in each group.Rats were given the relevant drugs respectively for 7 weeks.Finally the levels of fasting blood glucose (FBG),serum total cholesterol (STC),blood urea nitrogen (BUN),creatinine (Cr) and urinary protein (Upro) were detected.The kidney tissue was taken for histopathological observation.Results Compared with DN modelgroup [FBG,STC,BUN,Cr and Upro was (24.78±3.66)mmol/L,(4.07±1.32)mmol/L,(22.36±2.54)mmol/L,(86.78±7.47) μmol/L,(50.23±6.82)mg respectively],the rats in DN model group after treatment with common and superfine powder (medium and high dose groups) of Rhodiola rosea appeared different levels of improvement ofFBG [(18.67±2.74) mmol/L,(17.21 ±3.17)mmol/L,(15.48±2.46) mmol/L],STC [(3.33±0.87) mmol/L,(3.42 ± 0.74) mmol/L,(3.21 ±0.92)mmol/L],BUN [(15.43±2.04)mmol/L,(16.56±1.85)mmol/L,(12.44±1.36)mmol/L],Cr [(66.17 ± 4.43) μmol/L,(68.42 ± 5.06) μmol/L,(61.33±4.21)μmol/L] and Upro [(37.47±5.64) mg、(35.66 ± 4.72) mg,(27.37± 3.92) mg],P＜ 0.05.The pathologic changes of kidney tissue were improved,too.Conclusion Rhodiola rosea has a good renal protective effect in rats with DN.Furthermore,the superfine powder is more effective than the common powder in renal protective effects.

Clinical significance of determination of C-reactive protein, hemoglobin, erythrocyte sedimentation rate in the different stages of patients with multiple myeloma / 白血病·淋巴瘤

Objective To analyze the changes and clinical significance of C-reactive protein (CRP)、hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) in different disease stage of multiple myeloma according the international staging system. Method Thirty untreated MM patients with complete clinical records were included in the stndy. The multiple myeloma patients were classified into three groups according to international staging system (ISS).Thirty megaloblastic anemia patients of similar age 、sex、hemoglobin level as the observation group.Resulets The levels of CRP (24.17±9.87 mg/L)、Hb (71.72±13.27 g/L) and ESR (105.94±27.73 mm/h) of stage Ⅲ patients were statistically different with stage Ⅰ ( CRP 8.54±1.97 mg/L; Hb 91.00±9.92g/L; ESR 73.57±20.53mm/h)、Ⅱ patients ( CRP 14.89±5.51 mg/L; Hb 91.29±8.32g/L; ESR 67.00± 15.56 mm/h) separately (P＜0.05).The levels of CRP (19.40±10.17 mg/L) and ESR (91.90±29.70 mm/h) in the MM patients were significantly higher than that in the observation group Ⅰ ( CRP 7.52±1.57mg/L; ESR 20.20±8.04mm/h) (P＜0.05 respectively).CRP and ESR level in MM patients positively correlated with myeloma cell proportion and β2-microglobulin level (P＜0.05), while Hb level negatively correlated with myeloma cell proportion and β2-microglobulin level (P＜0.05),Conclusion The levels of C-reactive protein、hemoglobin and erythrocyte sedimentation rate are closely associated with the development of multiple myeloma. C-reactive protein and hemoglobin are relatively sensitive response to disease than erythrocyte sedimentation rate. There is a clear clinical implication in detecting the patient' s condition for progress and the prognosis.

Pharmacokinetic Study on Hyperoside in Beagle's Dogs / 中草药·英文版

Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study.Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs,using kaempferol as internal standard.The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase.The analytes were separated on a Diamonsil C18 column (250 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-buffer solution (0.1mol/L NH4Ac + 0.3 mmol/L EDTA-Na2)-acetic acid (60:40:1) and was delivered at a flow rate of 1mL/min.The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃.The sample injection volume was 20 μL.Data were collected and analyzed using the ANASTAR software.PK parameters were calculated with DAS software (2.0).Results Linear relationships were validated over the range of 0.01-1μg/mL for hyperoside (r =0.9997).The intra-and inter-day precision values for all samples were within 10.0％,and the accuracies of intra-and inter-day assays were within the range of 92.4％-102.4％.The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h,after a single ig administration (25 mg/kg).The mean PK parameters for male and female dogs were as follows:Cmax (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL,AUC0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h),t1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h,respectively.Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P ＞ 0.05).Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.

Study on toxicity of hyperoside in rat embryo-fetal development / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the toxicity of hyperoside in rat embryo-fetal development, in order to provide preference for safe use of drugs during gestation period.</p><p><b>METHOD</b>Healthy pregnant rats were randomly divided into hyperosid groups (30, 175, 1000 mg x kg(-1) x d(-1)), the positive control group (cyclophosphamide, 7 mg x kg(-1) x d(-1)) and the solvent control group (1% aqueous carboxymethylcellulose). These rats were orally administered with hyperosid or vehicle during 6-15 d after gestation and subcutaneously injected with cyclophosphamide during 11-13 d. Maternal clinical sign, abortions, premature deliveries and body weight were monitored throughout gestation. At termination (gestation days 20), pregnant females were evaluated for clinical symposiums, weight change, corpora lutea count, existence and death of embryos; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.</p><p><b>RESULT</b>All pregnant rats showed no significant abnormality in appearance, viscera and skeletal development. However, there was a difference between the high-dose group of hyperoside and negative control group in the fetus body weight, the length of the embryos and the length of tail (P < 0.05).</p><p><b>CONCLUSION</b>Pregnant women are suggested to cautiously use hyperoside because it shows certain impact on development of fetal rats under the experimental conditions.</p>

IL-17 contributes to autoimmune hepatitis / 华中科技大学学报（医学）（英德文版）

The role of interleukin-17 (IL-17) in autoimmune hepatitis (AIH) was investigated. A mouse model of experimental autoimmune hepatitis was established, and the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BL/6 mice. The IL-17 expression in serum and the livers of the mice models was detected by using ELISA and immunohistochemistry, respectively. IL-17 neutralizing antibody was used to study the biological effect of IL-17 in the experimental AIH. IL-17 neutralizing antibody in vivo administration alleviated the hepatic inflammation and ALT level in the AIH model. IL-17 in the peripheral blood mononuclear cells (PBMC) of AIH patients was measured by using real-time PCR method. The results showed that IL-17 level was significantly up-regulated in AIH patients and mice models. It was concluded that IL-17 contributed to the development of AIH and might be a potential therapeutic target of AIH.

Correlation of cyclooxygenase 2 expression with microlymphatic density and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the expression of cyclooxygenase-2 (COX-2) in esophageal carcinoma and its correlation with microlymphatic density (MLD), and to investigate the clinicopathological and prognostic significance of COX-2 and MLD in patients with esophageal cancer.</p><p><b>METHODS</b>COX-2 expression and MLD were detected by immunohistochemistry in 100 cases of esophageal squamous cell carcinoma. Follow up was available in 76 patients. Multivariable Cox regression was used to analyze the association between the laboratory indices and overall survival of patients with esophageal carcinoma.</p><p><b>RESULTS</b>COX-2 expression was present in 73% of patients. MLD in patients with high COX-2 expression (99.71±39.62) was significantly higher than that in those with low or no COX-2 expression (80.22±30.36) (P<0.05). No correlations were observed between the over expression of COX-2 and clinicopathologic parameters including tumor size and lymphatic metastasis (P<0.05). However, MLD was associated with lymphatic metastasis and the depth of invasion (P<0.05, P<0.01). In the 76 patients with followed up, the median survival was 25.5 months. Cox regression showed that the COX-2 expression, histological grade of the tumor and MLD were risk factors of overall survival of esophageal carcinoma.</p><p><b>CONCLUSIONS</b>COX-2 may contribute to the lymphangiogenesis in the tumor. COX-2 may be a new target point for the treatment of esophageal carcinoma. COX-2 expression and microlymphatic vessel density are of significant prognostic value for esophageal carcinoma.</p>

Effect of ultrasound microbubble carrying herpes simplex virus thymidine kinase on hepatocellular carcinoma in mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the effect of ultrasound microbubble carrying herpes simplex virus thymidine kinase hepatocellular carcinoma in mice.</p><p><b>METHODS</b>Kunming mice were inoculated subcutaneously with H22 tumor cells. 40 male mice bearing subcutaneous hepatoma were randomized into 4 groups: PBS (group A), HSV1-TK (group B), HSV1-TK (group C), and microbubble carrying HSV1-TK (group D) were injected into the tail vein every 3 days. Mice in group C and D were exposed to ultrasound. The expression of TK protein was detected by western blot. Ganciclovir (GCV) was intraperitoneally injected at a dose of 100 mg x kg (-1) x d(-1) in group B, group C and group D. The tumor size was measured every 2 days.</p><p><b>RESULTS</b>TK gene could be injected precisely into hepatocellular carcinoma with ultrasound monitor, and the expression of TK protein was found in all 4 groups. Expression in group D was higher than others (P < 0.05). The rate of tumor growth inhibition were 0 in group A, 3.90%+/-1.80% in group B, 22.70%+/-2.86% in group C, 41.25%+/-3.20% in group D (group B vs group C, P < 0.05; group D vs group C, P < 0.05; group D vs group B, P < 0.05).</p><p><b>CONCLUSION</b>Ultrasound microbubble not only improve target gene therapy, but also enhance transfection efficiency.</p>

The change of the hepatic fibrosis and pigment deposition in mice schistosomal liver fibrosis treated with combination of Anluohuaxian pilule and interferon-γ / 中华传染病杂志

Objective To evaluate efficacy and mechanism of Anluohuaxian pilule combined with interferon-γ in the treatment of schistosomal liver fibrosis. To preliminarily study on the relationship of pigment deposition in liver and schistosomal liver fibrosis. Methods Thirty Kunming mice were divided into the normal control group, the infection control group and the combination of Anluohuaxian pilule and Interferon-γ treated group. Schistosomal liver fibrosis model was established by infection with 40 Schistosoma japonicum cercariae. The treated group was treated by combination of Anluohuaxian pilule and Interferon-γ for 8 weeks. The changes of pigment deposition and hepatic egg granuloma in Schistosoma japonicum infected mice were observed. Expressions of collagen Ⅰ and Ⅲ were detected by immunohistochemistry. Transforming growth factor (TGF)-β1 was detected by fluorescent polymerase chain reaetion(PCR). Histopathology and computer image analysis were applied to evaluate the change in the liver tissues. Results The amount of pigment deposition in liver was related to the expression of TGF-β1 mRNA (correlation coefficient = 0. 8). Compared to the infection control group, combination of Anluohuaxian pilule and Interferon-γ can lessen hepatic fibrosis(P<0.05). The combination therapy can also make pigment deposition less and hepatic granuloma smaller than the infection control group(P<0. 05). Conclusions Pigment deposition in liver is related to the expression of TGF-β 1. Combination of Anluohuaxian pilule and Interferon-γ can lessen hepatic fibrosis in mice infected with Schistosoma japonicum. It's one mechanism to of the combination therapy down-regulate the expression of collagen Ⅰ, Ⅲ and TGF-β 1.

Tissue distribution of exendin-4 in rats / 中国药理学与毒理学杂志

AIM To investigate the tissue distribution of exendin-4 after administration in healthy rats. METHODS Exendin-4 was radioiodinated by the Iodo-GenTMmethod. Tissue distribution of [125I]exendin-4 was investigated after sc administration of [125I]exendin-4 at 3 μg·kg-1 in rats. Both total radioactivity and trichloroacetic acid (TCA) precipitated radioactivity were used to calculate the levels of [125I]exendin-4 in rats plasma and tissue samples after sc administration. RESULTS The tissue distribution of [125I]exendin-4 after sc injection showed substantial disposition in kidneys, lungs, bladder and pancreas. The rank order of normalized tissue distribution was kidneys＞lungs＞bladder＞pancreas＞intestine＞plasma＞adrenals>jejunum＞lymph＞liver＞spleen＞heart＞marrow＞thymus＞testicles＞brain＞muscle＞adipose. CONCLUSION [125I]Exendin-4 underwent a rapid and wide distribution in the tissues throughout the whole body within the time course examined. TCA precipitated radioactivity in kidneys was the highest, however, only trace amounts of [125I]exendin-4 was detected in the brain.

Evaluation on the safety of a group A + C meningococcal polysaccharide vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the safety of a group A + C meningococcal polysaccharide vaccine as part of a phase IV clinical trial.</p><p><b>METHODS</b>The study area was divided into 108 clusters according to the principle of cluster randomization, stratified and paired sampling methods. 54 out of 108 clusters served as observation groups were administered A + C vaccine, while the rest 54 groups were administered Vi polysaccharide vaccine. An adverse event surveillance system was established to monitor the adverse events following the vaccination campaign. Identical form and methods were used for data collection to investigate the adverse events following the vaccination of both A+ C vaccine and Vi vaccine.</p><p><b>RESULTS</b>34,543 people were vaccinated, including 18,167 of whom received A + C vaccine, while the other 16,376 received Vi vaccine. The rates of immediate injection reaction and unsolicited non-serious adverse events from A + C vaccine group were 0.44% and 0.38% while of Vi vaccine group were 0.79% and 0.73% respectively. At the solicited adverse event survey on 3-day-post-vaccination, 1239 vaccinees were followed-up including 771 received A + C vaccine and 468 received Vi vaccine. The local injection reaction rate of A + C vaccine group on the 1st day was significantly higher (X2 = 13.98, P = 0.0002) than that of Vi vaccine group. Neither the local injection reaction rate nor the system reaction rate between both groups was significantly different on 2nd and 3rd day, post vaccination. It was not statistically different when comparing fever onset rate between those who received vaccine and those who did not, in each vaccine group. There were no serious adverse events observed.</p><p><b>CONCLUSION</b>Results showed that the side effects of A + C vaccine and the Vi vaccine were mild and safe for vaccination campaigns targeting on populations at different age.</p>

Application of cluster randomization method on typhoid Vi vaccine trails / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.</p><p><b>METHODS</b>Simple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.</p><p><b>RESULTS</b>According to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.</p><p><b>CONCLUSION</b>Confounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.</p>