Dynamic changes in specific IgG antibodies induced by recombinant hepatitis E vaccine using different immunization strategies in mice / 中华微生物学和免疫学杂志

Objective:To observe the dynamic changes in specific IgG antibodies induced by recombinant hepatitis E vaccine using different immunization strategies in BALB/c mice.Methods:BALB/c, C57BL/6, NIH and KM mice were immunized intraperitoneally with serially diluted hepatitis E vaccine to select a mouse strain appropriately responding to hepatitis E vaccine. Then the selected BALB/c mice were randomly divided into three experimental groups, one-dose immunization group (0 week), two-dose immunization group (0 and 4 weeks) and three-dose immunization group (0, 4 and 12 weeks), and three adjuvant control groups with the same immunization strategy as the corresponding experimental group. Blood samples were collected from the intraocular canthus at different time points and serum antibody levels were detected quantitatively.Results:The BALB/c and NIH mice had proper responses to hepatitis E vaccine administrated at different doses than the C57BL/6 and KM mice, and the antibody positive conversion rates also showed a certain dose-effect relationship. Thus, the BALB/c mice were used as the animal model. The level of specific IgG antibodies in BALB/c mice immunized with one dose of vaccine reached a peak of 44.35 U/ml around the 10th week after the immunization, and then maintained at (5.52-13.28) U/ml after a decrease. The antibody level in the two-dose immunization group increased rapidly after the second immunization and peaked at the 8th week. From the 10th week, it gradually decreased and maintained at (16.50-32.54) U/ml. The trend of antibody changes in the three-dose immunization group was similar to that of the two-dose immunization group during the first 12 weeks, but a significant increase was induced after the third immunization and the level maintained at (62.65-72.61) U/ml for a long time, which was about nine times higher than that of the one-dose immunization group and three times of the two-dose immunization group.Conclusions:This study showed that BALB/c mice were suitable models to study the dynamic changes in specific IgG antibodies elicited by hepatitis E vaccine using different immunization strategies, which provided reference for future research on its in vivo efficacy.

Prognostic value of the tumor deposit in N0 gastric cancer by propensity score matching analysis / 中华胃肠外科杂志

OBJECTIVE@#To investigate the prognostic value of tumor deposits(TD)in N0 stage gastric cancer.@*METHODS@#A retrospective case-control study was performed on clinicopathological data of 751 N0 stage gastric cancer patients who underwent subsequent R0 gastrectomy from January 2011 to February 2013 at Zhengzhou University Affiliated Tumor Hospital. Patients were divided into TD-negative group (688 cases) and TD-positive group (63 cases). Propensity score matching was used to balance the covariances between the two groups, such as age, gender, differentiation degree, tumor location, T stage, perineural invasion, lymphovascular invasion, extent of resection, tumor size, surgical procedure,and chemotherapy. Matching was performed by the minimal adjacent method of 1:2 pairing. The survival analysis was carried out using Kaplan-Meier method,and differences between the curves were detected by log-rank test. Cox proportional hazard model was used to perform univariate analysis and multivariate analysis.@*RESULTS@#After matching,56 patients were allocated into the TD-positive group and 112 patients into the TD-negative group, and the baseline of clinicopathological data of 2 groups matched well (all P>0.05). The median follow-up time was 55.2 (12.0-83.2) months, and 3 patients were lost to follow-up (died of other diseases). In TD-positive group, 38 patients died of gastric cancer and 1 died of other disease. In TD-negative group, 52 patients died of gastric cancer and 2 died of other diseases. The TD-positive group had lower 5-year survival rate than TD-negative group (31.0% vs. 52.9%,χ²=6.230, P=0.014). Subgroup analysis showed that the 5-year survival rate of T1-2 stage TD-positive patients was significantly lower than that of T1-2 stage TD-negative patients (47.1% vs. 92.6%, χ²=11.433,P<0.001),while the difference between two groups with T3-4 stage (23.8% vs. 40.0%, χ²=2.995,P=0.084)was not significant. In patients receiving chemotherapy, the 5-year survival rate of TD-positive group was significantly lower than that of TD-negative group(34.1% vs. 54.8%, χ²=4.122, P=0.042). Further subgroup analysis showed that patients receiving postoperative chemotherapy of TD-positive group both in T1-2 stage (63.6% vs. 100%, χ²=3.830,P=0.048) and in T3-4 stage (24.2% vs. 48.4%, χ²=4.740,P=0.029) had significantly lower 5-year survival rates than those of TD-negative group. However,T1-2 stage TD-positive patients receiving chemotherapy had significantly higher 5-year survival rate as compared to those without receiving chemotherapy(63.6% vs. 16.7%, χ²=5.474,P=0.019).Univariate analysis revealed T stage (HR=1.829, 95%CI:1.490-2.245, P<0.001),perineural invasion (HR=2.620, 95%CI:1.617-4.246,P<0.001),tumor size (HR=1.646, 95%CI:1.078-2.512, P=0.021),TD(HR=1.691,95%CI:1.112-2.572,P=0.014) were associated with the prognosis of patients with gastric cancer. Multivariate analysis showed TD-positive (HR=2.035, 95%CI:1.325-3.126, P=0.001), later T stage (HR=1.812, 95%CI: 1.419-2.313,P<0.001), perineural invasion (HR=1.782,95%CI:1.058-3.002,P=0.030) were independent risk factors for the prognosis of gastric cancer.@*CONCLUSIONS@#TD is an independent risk factor for N0 stage gastric cancer,and may be closely related to T stage. Patients with TD-positive stage T1-2 should receive chemotherapy, but the prognosis of TD-positive patients undergoing adjuvant chemotherapy is poorer as compared to TD-negative patients. Therefore, more individualized treatments should be administrated.

Correlation between Prognostic Nutritional Index and Pathologic Complete Response after Neoadjuvant Chemotherapy in Gastric Cancer Patients by Propensity Score Matching / 中国医科大学学报

Objective To investigate the correlation between the rate of pathological complete response (pCR) and prognostic nutritional index (PNI) in gastric cancer patients who underwent neoadjuvant chemotherapy (NAC). Methods A total of 278 advanced gastric cancer patients who underwent NAC and R0 gastrectomy with D2 lymphadenectomy between January 2012 and March 2017 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups (PNI＜45, 157 patients; PNI≥45, 121 patients). Multivariate analysis was used to determine the independent risk factors of the pCR rate in gastric cancer patients who underwent NAC. Results PNI (OR:3.026;95％ CI:1.261, 7.260;P = 0.013), differentiation (OR:0.470;95％ CI:0.270, 0.819;P = 0.008), and tumor location (OR:0.341;95％ CI:0.164, 0.708;P = 0.004) were the independent risk factors associated with the pCR rate of the gastric cancer patients who underwent NAC. After PSM, PNI (OR:2.728;95％ CI:1.130, 6.587;P = 0.026) was the independent risk factor associated with the rate of pCR after NAC. Conclusion Gastric cancer patients who underwent NAC with low PNI are less likely to get pCR than those with normal PNI.

Development and verification of indirect immunofluorescence assay for detection of baculovirus titer / 中华微生物学和免疫学杂志

Objective To develop, optimize and preliminarily verify an indirect immunofluores-cence assay ( IFA) for detecting the titer of recombinant baculovirus. Methods Conditions for performing IFA, including cell concentration, co-incubation time, reaction temperature, dilution ratio, reaction time and types of fixative solution, blocking liquid and antibodies, were optimized to establish an IFA method for the detection of baculovirus titer. Specificity, accuracy, reproducibility and intermediate precision of the es-tablished assay were verified. And the results were compared with those of baculovirus rapid titer kit. Re-sults The optimal cell concentration for coating was 0. 6×106 cell/ml, and the optimal reaction time be-tween viruses with cells was 3 d. The optimal conditions for conducting IFA were as follows: formaldehyde buffered acetone (-20℃) was used as fixative, normal goat serum was used as blocking liquid and the first and second generation antibodies at a dilution of 1 : 200 were incubated at 37℃ for 1 h, respectively. Spe-cific fluorescence was observed only in baculovirus but not in others by using the method. No significant difference in virus titers was observed between the established IFA and baculovirus rapid titer kit. The two methods showed a good linear correlation (R2=0. 996). Coefficients of variation for evaluating the reproduc-ibility and intermediate precision were less than 10％. Conclusion IFA for the detection of baculovirus ti-ter was established with good specificity, accuracy, reproducibility and intermediate precision.

Prognostic analysis of neoadjuvant chemotherapy for locally advanced gastric cancer with propensity score matching method / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the effects of neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer using propensity score matching method.</p><p><b>METHODS</b>Clinical data of patients with locally advanced gastric cancer undergoing open D2 radical gastrectomy between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Sixty-five patients receiving neoadjuvant chemotherapy (NAC) were allocated into the NAC group and 1243 patients receiving postoperative adjuvant chemotherapy (AC) were allocated into the AC group.</p><p><b>INCLUSION CRITERIA</b>(1) age ranged from 18 to 75 years old, and biopsy specimen was confirmed as adenocarcinoma; (2) all the operative procedures were open D2 radical gastrectomy;(3)image examinations showed no distant metastasis or other unresectable factors.</p><p><b>EXCLUSION CRITERIA</b>no open D2 radical gastrectomy, undergoing laparoscopic surgery, neoadjuvant chemotherapy course <2 cycles, without adjuvant chemotherapy, history of other malignancies, severe complications, incomplete data. SOX (tegafur-gimeracil-oteracil plus oxaliplatin) or XELOX (capecitabine plus oxaliplatin) was used as neoadjuvant and postoperative adjuvant chemotherapy regimen. One-to-two propensity score matching was performed to balance the covariance between two groups. Survival was analyzed using the Kaplan-Meier method. Differences between the curves were tested using log-rank test.</p><p><b>RESULTS</b>After balancing the covariates including gender, age, tumor location, degree of differentiation, clinical stage, chemotherapy regimen, chemotherapy course and surgical approach, 195 patients were enrolled, including 65 patients of the NAC group and 130 patients of the AC group. The number of harvested lymph nodes in NAC and AC group was 22.3±4.6 and 22.6±5.1 respectively, without statistically significant difference(t=1.125, P=0.263). Pathological response assessment for NAC group showed TRG0 in 6 cases, TRG1 in 8 cases, TRG2 in 17 cases, TRG3 in 34 cases; sensitive (TRG 0 to 2) in 31 cases (47.7%), non-sensitive in 34 cases (52.3%). The 3-year progression-free survival rate of NAC and AC group was 73.6%(95%CI: 62.8-84.3) and 69.9%(95%CI:62.1-77.7) respectively, which was not significantly different(P=0.361). The 3-year overall survival rate of NAC and AC group was 80.0%(95%CI:70.2-89.8) and 74.6%(95%CI:67.2-82.0) respectively, which was not significantly different as well(P=0.387). Subgroup analysis revealed that the 3-year progression-free survival rate and 3-year overall survival rate of sensitive patients in NAC group were 83.3%(95%CI:70.0-96.6) and 87.1%(95%CI:75.3-98.9) respectively, which were significantly higher than 62.4%(95%CI:46.1-78.7, P=0.037) and 70.2%(95%CI:54.7-85.7, P=0.033) of non-sensitive patients in NAC group, and those in AC group(P=0.044 and P=0.040).</p><p><b>CONCLUSIONS</b>Effects of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer are similar. Patients who are sensitive to neoadjuvant chemotherapy have better prognosis. It may be beneficial to improve prognosis that some appropriate patients with locally advanced gastric cancer are screened for neoadjuvant chemotherapy.</p>

Clinical features and prognosis analysis of 21 gastric cancer patients with pathological complete response after neoadjuvant chemotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical features and prognosis of gastric cancer patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC).</p><p><b>METHODS</b>Clinical data of 159 gastric cancer patients who received NAC followed by surgical resection between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were collected and clinical features of those with pCR were analyzed retrospectively. Kaplan-Meier method was used to estimate 3-year overall survival (OS) rate and recurrence-free survival (RFS) rate. Recurrence factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model.</p><p><b>RESULTS</b>A total of 21 patients(13.2%) achieved pCR, including 13 male and 8 female cases, with the median age at diagnosis of 56 (40 to 70) years. Eleven cases were differentiated tumor and 10 were undifferentiated. Six cases were in clinical baseline stage II(, and 15 were in III(. Five cases received the mFOLFOX6 (oxaliplatin + leucovorin +5-FU), 6 received the SOX (oxaliplatin +S-1), 4 received the XELOX (oxaliplatin + capecitabine), 2 received the EOX (epirubicin + oxaliplatin +capecitabine) and 4 received the DOX (docetaxel + oxaliplatin +capecitabine) chemotherapy regimens. Two cases achieved CR, 18 achieved PR, and 1 was SD after NAC. The median (range) course of preoperative and postoperative chemotherapy were 4(2 to 5) and 2(0 to 5) . All the patients underwent R0 resection plus D2 lymphadenectomy, and 4 cases were performed with proximal gastrectomy, 3 cases were performed with distal gastrectomy, 13 cases were performed with total gastrectomy, and one case was performed with total gastrectomy plus pancreatic splenectomy. Pneumonia, abdominal bleeding and infection, anastomotic leakage, and gastroplegia occurred respectively in one case, who all were cured by conservative treatment. The median follow-up of the survivors was 39.3 (range 22.7 to 56.9) months. Three cases died of recurrence: 1 case in the liver, 1 in the lung, and 1 in the brain. Two cases developed recurrence and survived: 1 in the liver and 1 in celiac lymph nodes. The overall survival and 3-year recurrence-free survival rates were 90.2%(95%CI: 100 to 77.3) and 90.5%(95%CI: 100 to 78.0). Fourteen cases did not complete scheduled chemotherapy course, and the overall 3-year survival rate was 85.1%. Older age(>50 years old)(P=0.028, RR=0.063, 95%CI: 0.005 to 0.743) and no postoperative complication (P=0.023, RR=0.065, 95%CI: 0.006 to 0.689) were identified as independent prognostic factors with Cox multivariate analysis.</p><p><b>CONCLUSION</b>Patients diagnosed as gastric cancer with pCR after NAC have good prognosis, but the pCR ratio is low, and those with younger age and more postoperative complications may have higher risk for recurrence and metastasis.</p>

Expression of heat shock protein 27, 60 and 90 in gastric cancer and its clinical value / 中国免疫学杂志

Objective: To investigate the expression of HSP-27,-60 and -90 in gastric cancer and its clinical significance. Methods:66 cases of gastric carcinoma was detected by immunohistochemistry HSP-27,60 and 90 of the expression and clinical significance of combined with clinical and pathological characteristics, tumor cell proliferation and survival analysis of three kinds of heat shock protein expression. Results: HSP-27,-60 and -90 were highly expressed in gastric cancer tissues. HSP-27 expression and tumor size (pT,P=0. 026),organ metastasis (pM,P=0. 046) and pathological staging (P=0. 041),HSP-27 staining intensity and lymph node status were significantly correlated ( pN, P=0. 042 ) . HSP-60 expression was associated with gender ( P=0. 011),and HSP-60 staining intensity was associated with age (P=0. 027) and tumor grade (P=0. 031). There was no correlation between HSP-90 expression and the clinical pathological parameters of this study; however, the intensity of HSP-90 staining was significantly correlated with tumor size (P=0. 020,pT). Single factor analysis showed that HSP-90 was significantly associated with longer survival (P=0. 033). Multivariate analysis demonstrated that HSP-90 was highly expressed as an independent prognostic factor for gastric cancer (P=0. 026). Conclusion: the HSP-27,-60 and -90 and some clinical pathological parameters. These parameters is very important for the treatment of patients with gastric cancer. The high expression of HSP-90 in patients with gastric cancer were inde-pendent prognostic indicators.

Effect of irinotecan hydrochloride injection on serum GPX3 and WISP2, FGFBP1 in tumor tissue fluid of patients with advanced rectal cancer / 中国生化药物杂志

Objective To analyse the effect of irinotecan hydrochloride injection on serum glutathione peroxidase 3 (GPX3), and WNT1 induced signaling pathway protein 2 (WISP2) and fibroblast growth factor binding protein 1 (FGFBP1) in tumor tissue fluid of patients with advanced rectal cancer.Methods 90 patients who were diagnosed with advanced rectal cancer in the hospital were collected.All patients were randomly divided into experimental group and control group,control group were treated with oxaliplatin +calcium folinate +fluorouracil chemotherapy, and experimental group were treated with oxaliplatin +calcium folinate +irinotecan hydrochloride injection chemotherapy.The treatment were repeated every four weeks, a total of six times.The serum GPX3 content, and WISP2, FGFBP1 levels in tumor tissue fluid were detected in two groups pre-and post treatment.The clinical efficacy was evaluated.ResuIts Compared with control group, the serum level of GPX3 in experimental group increased significantly (P<0.05);WISP2 level in tumor tissue fluid of experimental group increased significantly (P<0.05);FGFBP1 level in tumor tissue fluid of experimental group decreased significantly ( P<0.05 ) .The total efficiency of experimental group was higher than that of control group ( 64.44%vs.42.22%;χ2 =4.46,P<0.05), and the clinical benefit rate of experimental group was significantly higher than that of control group(93.33%vs.75.56%;χ2 =5.41,P<0.05).ConcIusion The irinotecan hydrochloride injection could increased levels of serum GPX3 and WISP2 in tumor tissue fluid, reduce FGFBP1 level in tumor tissue fluid, which has good clinical curative effect.

Secondary prevention and treatment of precancerous lesions of breast cancer / 国际外科学杂志

ObjectiveTo practice second-level prevention of breast cancer, conduct serial experiments on blocking precancerous change of breast cancer thus reduce its incidence rate. MethodsAfter the segment resection of primary lesions the breast precancerous lesions with ductal hyporplasia (DH) atypical ductal hyperplasia (ADH) and ductal intraepithelial neoplasia (DCIS), lobular intraepithelial neoplasia (LCIS) ,detected hormone receptors ER, PR and c-erbB-2, P53 were detected. With individualized comprehensive treatment, the positive patients with ER and PR was treated with tamoxifen; the postmenopausal patients took anastrozole to reduce the levels of estrogen; the positive patients with c-erbB-2 were treated with chemotherapy and the combined treatment; the patients with preoperative diagnosis of malignant cells were taken with the ipsilateral axillary lymph node dissection; all patients were observed and followed up.ResultsThere were 126 cases of the breast precancerous lesions from 1992 to 2008, including 75 cases of ADH with the positive rates of ER and PR 86.6％, c-erbB-2 1.33％, P53 0; 51 cases of DCIS and LCIS with the positive rates of ER and PR 84.6％, c-erbB-2 4％ ,P53 4％ ; Axillary lymph node reactive hyperplasia were 0/9 - 0/18. ConclusionsBreast precancerous lesions of ADH, DCIS, LCIS are local symptoms of the systemic disease, the segment resection of primary lesions and comprehensive treatment ( endocrine, chemotherapy, radiotherapy) based on immunohistochemical expression are effective through which the incidence rate of breast cancer could be largely controlled or suppressed.