Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In ...Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.展开更多
AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, ...AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.展开更多
Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱstudy of gemcitabine combined with platinum chemother...Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱstudy of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50.5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95%CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P=0.061). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 (36.4%) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.展开更多
Human urotension-Ⅱwas synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.Disulphide bridge was formed on solid phase with the irradiation of microwave,then...Human urotension-Ⅱwas synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.Disulphide bridge was formed on solid phase with the irradiation of microwave,then the whole peptide was cleaved from the resin.The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.展开更多
This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,espec...This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,especially for new reactor design produced fluid-induced vibration model test,theoretical analysis and testing in-built reactor;aiming at two-loop NSSS a series improvement made for safety systems and related safety analysis to enhance their reliability and redundancy;according to specialty of two-loop NSSS an optimization made for NPP parameters and design of related equipments,for the purpose to make the output of NPP maximal;design of main reactor building and T-G building also improved according to characteristics of two-loop NSSS and site conditions.CRDM and refueling machine are researched and manufactured on base of self-reliance,their performance are better than design requirements,large portion of key equipments are localized through different way.In construction first time realized the integrated erection of containment dome.During the commissioning non-nuclear steam driving of T-G set,as well as 500 kV high voltage rising using emergent diesel generator,etc.are carried out.In period of operation still continuous innovation and improvement are made,so that to keep the good record of operation.展开更多
Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial c...Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial communities associated with the compost samples were far richer in composition when determined by ARDRA compared with traditional methods based on bacterial isolation.Furthermore,the composition of the communities,especially in terms of the dominant bacteria during each of the four treatment stages(beginning of Phase Ⅱ,after pasteurization,5 days aeration,end of Phase Ⅱ,respectively),were very different.Restriction endonuclease digestion of mainly bacterial clones from four 16S rDNA libraries,C1,C3,C6 and C7,previously constructed on the basis of 16S rDNA fragments amplified from the four different stages of the Phase Ⅱ composting process,revealed the presence of unique microbial types.Thermophilic bacteria belonging to the Bacilli,and previously unreported strains of Trichococcus,Planococcus,Caryophanon,and subclass γ-Proteobacteria,were identified among the clones from the compost sampled during the aeration period(C6).Bacteria belonging to Thermus thermophilus and subclass α-Proteobacteria were detected in C1 and C7 composts sampled at the beginning and the end of Phase Ⅱ,respectively.Clones of some uncultured bacteria were also scored.展开更多
文摘Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.
文摘AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.
文摘Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱstudy of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50.5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95%CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P=0.061). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 (36.4%) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.
文摘Human urotension-Ⅱwas synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.Disulphide bridge was formed on solid phase with the irradiation of microwave,then the whole peptide was cleaved from the resin.The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.
文摘This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,especially for new reactor design produced fluid-induced vibration model test,theoretical analysis and testing in-built reactor;aiming at two-loop NSSS a series improvement made for safety systems and related safety analysis to enhance their reliability and redundancy;according to specialty of two-loop NSSS an optimization made for NPP parameters and design of related equipments,for the purpose to make the output of NPP maximal;design of main reactor building and T-G building also improved according to characteristics of two-loop NSSS and site conditions.CRDM and refueling machine are researched and manufactured on base of self-reliance,their performance are better than design requirements,large portion of key equipments are localized through different way.In construction first time realized the integrated erection of containment dome.During the commissioning non-nuclear steam driving of T-G set,as well as 500 kV high voltage rising using emergent diesel generator,etc.are carried out.In period of operation still continuous innovation and improvement are made,so that to keep the good record of operation.
基金Supported by project of China Agricultural Ministry(No.nyhyzx-07-008)
文摘Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial communities associated with the compost samples were far richer in composition when determined by ARDRA compared with traditional methods based on bacterial isolation.Furthermore,the composition of the communities,especially in terms of the dominant bacteria during each of the four treatment stages(beginning of Phase Ⅱ,after pasteurization,5 days aeration,end of Phase Ⅱ,respectively),were very different.Restriction endonuclease digestion of mainly bacterial clones from four 16S rDNA libraries,C1,C3,C6 and C7,previously constructed on the basis of 16S rDNA fragments amplified from the four different stages of the Phase Ⅱ composting process,revealed the presence of unique microbial types.Thermophilic bacteria belonging to the Bacilli,and previously unreported strains of Trichococcus,Planococcus,Caryophanon,and subclass γ-Proteobacteria,were identified among the clones from the compost sampled during the aeration period(C6).Bacteria belonging to Thermus thermophilus and subclass α-Proteobacteria were detected in C1 and C7 composts sampled at the beginning and the end of Phase Ⅱ,respectively.Clones of some uncultured bacteria were also scored.
