Object To evaluate the efficacy and toxicity of L-asparaginase based regimen for extranodal nasal type NK/T cell lymphoma (ENKTL).Methods 36 patients were treated with L-asparaginase based regimen from February 2008 to November 2011. 20 stage Ⅰ /Ⅱ patients were administered with VLD regimen based chemo-radiotherapy. 4 of 16 stage Ⅲ/Ⅳ patients received modified SMILE regimen chemotherapy, followed by involved field radiation therapy (IFRT), while others received modified SMILE regimen chemotherapy alone.Results Among 36 patients,35 were eligible for treatment response evaluation.The overall response rate (RR) was 68.6％ (24/35) with complete response (CR) rate of 54.3％ (19/35).After the median follow-up of 13.5 (range 3-31) months,for all patients,the 1-year overall survival (OS) rate was 82 ％,and the rate of progression-free survival (PFS) at 1 year was 65 ％.The patients who attained response with treatment showed better 1-year OS (93 ％) and PFS (80 ％) as compared with patients without response (35 ％; 33 ％),and the differences were statistically significant (x2=13.909,P =0.000; x2=8.216,P =0.004).The major adverse event was myelosuppression. No chemotherapy-related mortality occurred. Conclusion L-asparaginase based regimen is obviously effective and well tolerant for ENKTL. The large prospective clinical trials of L-asparaginase based regimen in the first-line treatment for ENKTL are worth for further investigation.

ObjectiveTo investigate its dynamic characteristics and pathological mechanism on magnatic resonance diffusion weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model.MethodsForty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity was opened.Forty VX-2 tumor models from them were divided into four groups.DWI was performed periodically and respectively for each group after chemoembolization.All VX-2 tumor samples of each group were studied by pathology.The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values.The statistical significance between different time groups,different area groups,or different b-value groups was calculated using SPSS 12.0 software.ResultsWhen b-value was 100 s/mm2,ADC values in the area of VX-2 tumor periphery,VX-2 tumor central,or normal liver parenchyma around tumor became gradually low in sixteen hours after chemoembolization,and were the lowest at sixteenth hour,and then they increased gradually from sixteenth hour to fourty-eighth hour after chemoembolization.The distinction of ADC between different time groups was significant,respectively ( F =7.325,P ＜ 0.01 ; F =2.496,P ＜ 0.05 ; F =6.856,P ＜0.01 ).Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor increased quickly in sixteen hours after chemoembolization; however,from sixteenth hour to forty-eighth hour,cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at first and then increased continually.Cellular necrosis in the area of VX-2 tumor periphery after chemoembolization was more significant than that before chemoembolization.The areas of dead cells in VX-2 tumors manifested low signal and high ADC value while the areas of viable cells manifested high signal and low ADC value.ConclusionsDWI is able to detect and discriminate tumor necrotic areas from viable cellular areas before and after chemoembolization.ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema,tissue cellular death,and microcirculation disturbance after chemoembolization.

Objective To investigate dynamically characteristics of apparent diffusion coefficient (ADC) of MR diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model.Methods Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity was opened.DWI was carried out periodically and respectively on seventh,fourteenth,and twenty-first day after implantation.Part samples of VX-2 tumors were studied by pathology.The distinction of VX-2 tumors on DWI was assessed by their ADC values.The statistical significance between different time groups,different area groups,or different b-value groups was calculated using SPSS12.0 software,respectively.Results ADC values of 47 VX-2 tumors in the area of tumor periphery,tumor center,and normal parenchyma around tumor were greater when b-value was 100 s/mm2 than those when b-value was 300 s/mm2 and the distinction of VX-2 tumor ADC in the area of tumor periphery,tumor center,and normal parenchyma around tumor between different b-value groups was significant,respectively( F =17.964,P ＜0.01 ; F =13.986,P ＜0.01 ; F =128.681,P ＜0.01 ).The ADC values in the area of normal liver parenchyma around tumor were greater than those in the area of VX-2 tumor periphery and tumor center when the b-value was 100 or 300 s/mm2.When b-value was the same( 100 or 300 s/mm2),the distinction of VX-2 tumor ADC between different areas was significant( F =176.586,P ＜0.01 ; F =55.089,P ＜0.01 ).The ADC of VX-2 tumor in the area of tumor periphery and tumor center became gradually low from seventh to fourteenth or twenty-first day after implantation and the distinction of ADC between different time groups but the area same (?) was significant( b =100 s/mm2,F =48.211,P ＜0.01 ;b =300 s/mm2,F =20.955,P ＜0.01 ).There were not obvious cellular necrosis in VX-2 tumors on seventh and fourteenth day after implantation but ADC of VX-2 tumor decreased unobviously because of cellular edemata in or around tumors.There were obvious cellular necrotic areas in VX-2 tumors on the twenty-first day after implantation.ADC of viable tumor cells in VX-2 tumors were lower on DWI than that in the area of normal liver parenchyma around tumor and ADC of dead tumor cells in VX-2 tumors were unequal,including high values,equal values,and low values but they were higher than that in the area of normal liver parenchyma around tumor after dead tumor cells had been liquified or had become cystic.Conclusions ADC is able to reflect objectively the diffusion of water molecules in the tumor and to reflect indirectly the degree of the growth and liquified necrosis of a tumor.ADC has an important and potential value in monitoring dynamical tumor growth and in evaluating malignant degree and therapeutic effect.

OBJECTIVE: To analyze the clinical characteristics of primary gastric lymphoma (PGL) and to improve its diagnosis and treatment. METHODS: The clinical manifestations, diagnosis, treatments and history of 50 PGL patients, who were hospitalized from September 2005 to September 2009, were reviewed and analyzed. RESULTS: The main manifestation of PGL was epigastric pain with infrequent systemic symptoms, such as stomach ache, abdominal discomfort, vomit, black stool, loss of appetite, fever, feeble, and skinny. Pathological examination indicated that only 1 patient had T cell lymphoma while the rest 49 had B cell lymphoma. Fourteen had mucosa-associated lymphoid tissue lymphoma (MALT), 35 had diffuse large B cell lymphoma (DLBCL), and 2 had both DLBCL and MALT (DLBCML). All the 50 patients received chemotherapy, and 12 underwent surgical treatment besides chemotherapy. Fourteen out of the 49 patients with B cell lymphoma received rituximab together with chemotherapy, and 35 received chemotherapy alone. The 2-year survival rate in the patients receiving rituximab together with chemotherapy was higher than that in the patients receiving chemotherapy alone (85.7% vs 77.1%, P< 0.05). The 2-year survival rate in patients of clinical stage I-II was higher than that in patients of clinical stage III-IV (90.9% vs 71.4%, P< 0.05). CONCLUSION The main clinical manifestation of PGL patients is non-specific gastrointestinal symptoms, among which abdominal pain is most common. The clinical examination mainly relies on pathological examinations, and the most common pathological type of primary gastric lymphoma is DLBCL. The main treatment is chemotherapy, and the prognosis is related to the clinical stage and the use of rituximab. After the treatment, the 2-year survival rate in the 50 patients reaches 80.0%.
Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Humans ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Non-Hodgkin ; diagnosis ; drug therapy ; pathology ; Prognosis ; Retrospective Studies ; Rituximab ; Stomach Neoplasms ; diagnosis ; drug therapy ; pathology ; Survival Rate

OBJECTIVE: To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy. METHODS: The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology. RESULTS: The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS. CONCLUSION High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; Thymidylate Synthase ; genetics ; metabolism ; Treatment Outcome ; Tubulin ; genetics ; metabolism

Objective To investigate whether the host animals of Yulong plague foci carry Yersiniapestis phage,and to identify isolated plague phage.Methods Rodent specimens were collected in 5 villages of Yulong plague foci in spring and autumn of 2016,respectively.Vaccine strain EV76 was used as breeding bacteria.Phage was isolated from the specimens by double-layer plate method and plaque morphology was identified.Results ① Totally 409 samples collected in spring failed in phage isolation.A total of 40 of Yersinia pestis phages were isolated from 444 samples in autumn,and the total isolation rate was 9.01％ (40/444).② The Yersinia pestis phages were isolated in all of 5 villages,and the isolation rate was of no significant difference (x2 =5.055,P ＞ 0.05).③ Of the 40 strains of phage,37 strains were isolated from Apodemus chevrieri,2 strains from Eothenomys Miletus and 1 strain from Crocidura Dracula.④Based on the appearance,the plaque of the phage was divided into three:large (diameter 1.5-2.5 mm),middle (0.5-＜ 1.5 mm) and small (＜ 0.5 mm).Conclusion There is a higher number of plague phage in the host animals of the plague foci in Yulong County of Yunnan Province,the plaques are diverse in morphology,and their biological characteristics may be polymorphic.

Objective:To investigate whether the squirrels in Yunnan Province carried Yersinia pestis phages and their epidemiological significance. Methods:From 2015 to 2018, plague host animals were investigated in five of Yunnan plague foci and non-plague foci. The spleen, liver and intestinal specimens of the squirrels captured in the investigation were taken and stored at low temperature for later use. Intestinal specimens with PBS solution, were filtered by 0.22 μm and added to LB liquid medium containing 100 μl suspension of plague vaccine strain (EV76) and then oscillated in a constant temperature gas bath at 28 ℃ and 220 r/min for 18 to 24 h. The double-layer plate method was used to isolate and observe the growth of plaque. The morphology and structure of Yersinia pestis phages were observed under electron microscope. Meanwhile, spleen, liver and intestinal specimens were taken for detection of Yersinia pestis specific marker gene caf1. Results:A total of 10 squirrels were captured (8 Callosciurus erythraeus and 2 Dremomys pernyi), and four Yersinia pestis phages were isolated (2 in Callosciurus erythraeus and 2 in Dremomys pernyi). Two were isolated from non-plague foci (Yongshan County), two from house rats plague foci (Mile County and Xinping County), and none was isolated from wild radents plague foci (Jianchuan County and Eryuan County). By naked eye observation, two bacteriophages from the plague foci produced transparent plaques and grew well, while two bacteriophages from non-plague foci produced translucent plaques and with poor growth. By electron microscopy, these Yersinia pestis phages were of typical Myoviridae family, their head diameter was about 40 nm, muscle tail was about 120 nm, and tail filament cluster was slightly visible at the end of muscle tail. And all the 10 samples of squirrels were negative of plague-specific caf1 gene. Conclusions:The proportion of plague phages carried by Yunnan squirrels is relatively high. Although the detection of caf1 is negative. Squirrels may be a carrier of plague transmission due to the existence of Yersinia pestis phages.

Objective:To explore the biochemical characteristics, virulence factors and other phenotypes of the strains of Yersinia pestis isolated in Jianchuan County Yunnan Province in 2017, and to analyze the nature and source of the new plague epidemic. Methods:Three strains of Yersinia pestis (JC109 rat, JC109 fleas and JC113) isolated from Daqing Village, Jinhua Town, Jianchuan County, Dali Prefecture, Yunnan Province in 2017, and 2 associated strains of Yersinia pestis (LJ01 in Yulong County, Lijiang City and LJ04 in Gucheng District of Lijiang City), 5 control strains ( Yersinia pestis JC1332, LJ485, BN2636, EV-76 and Yersinia pseudotuberculosis PST-1), preserved by the Central Laboratory of Yunnan Institute for Endemic Disease Control and Prevention were collected. The biochemical characteristics and ecotypes of Yersinia pestis were analyzed by using arabinose, rhamnose, denbiose, maltose and glycerol fermentation experiments and nitrate reduction experiments. Combining pigmentation factor (pgm), virulence antigen (VW) detection and nutritional requirements test results to determine the virulence of Yersinia pestis. Results:The Yersinia pestis JC109 rat, JC109 fleas and JC113 all fermented arabinose, maltose and glycerol, but didn't ferment rhamnose and denbiose; and the nitrate reduction test was positive. The ecological type belonged to the Himalayan Marmot plague strain of Qinghai-Tibet plateau. The virulence factors pgm and VW tests were positive, the nutritional requirement type was phenylalanine dependent and glutamate independent. It had the same phenotype as the LJ01 strain, but different from the JC1332 strain. Conclusions:The newly isolated strains in Jianchuan County are the same as those in the Lijiang Yulong wild rodent plague foci. This outbreak may have been imported from the Lijiang Yulong wild rodent plague foci to the south.

Objective:To study the basic situation of Yunnan Province Suncus murinus carrying plague phage and to explore its epidemiological significance. Methods:From 2015 to 2018, a survey of plague host animals was carried out in 10 investigation sites in the historical plague foci, new plague foci (after 1982) and stubborn plague foci of domestric mouse in Yunnan Province. The plague phage was isolated and cultured from the intestinal specimens of Suncus murinus. The growth of plaque was observed by double-layer plate method, and the morphology and structure of plague phage were observed under electron microscope. At the same time, intestinal samples were taken to detect the structural gene caf1 of F1 antigen of Yersinia pestis. Results:In this study, a total of 157 Suncus murinus were captured and 16 strains of plague phage were isolated, with a total isolation rate of 10.19%. There was no difference in plague phage isolation rate between historical plague foci (10.00%, 1/10) and stubborn plague foci (16.22%, 12/74), new plague foci (4.11%, 3/73, χ 2 = 0.00, P = 0.965; Fisher test, P = 1.000). However, there was a difference in plague phage isolation rate between stubborn plague foci and new plague foci (χ 2 = 5.88, P = 0.015). There was no significant difference in the isolation rate of plague phage among different sex, growth period and habitat ( P > 0.05). The plaque morphology of the isolated plague phage was diverse, of which four strains were myotavirus phages; and all samples were negative for F1 antigen structural gene caf1. Conclusions:Suncus murinus is widely distributed in the domestic mouse plague foci in Yunnan Province, and the animals carry a certain number of plague phage. Regular surveillance of Suncus murinus and their plague phage has a certain guiding significance for the surveillance and early warning of plague in Yunnan Province.

Yersinia pestis phage is a virus that is parasitic within Yersinia pestis and can specifically lyses Yersinia pestis. The adsorption sites of phage infesting host bacteria are called receptor binding protein (RBP), including extracellular membrane protein, lipopolysaccharide, teichoteic acid, pili, flagella, capsular polysaccharide, etc., of which extracellular membrane protein and lipopolysaccharide are the receptors of Yersinia pestis phage. RBP plays a decisive role in the process of Yersinia pestis phage infecting Yersinia pestis. Therefore, the classification, isolation and application of Yersinia pestis phage are summarized; the research progress in identification and structure of Yersinia pestis phage receptor is analyzed, which is helpful in understanding the cleavage mechanism of Yersinia pestis phage and the interaction mode with Yersinia pestis from the molecular level, and provide more powerful support for in-depth study on Yersinia pestis phage receptor.