Background: The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (...Background: The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen. Methods: A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration ofcorticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of tbllow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS). Results: The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P 0.021 ). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P 〈 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively. Conclusions: Addition of TMZ chemotherapy in the early break of the standard concomi展开更多
The separated turbulent flow around a circular cylinder is investigated using Large-Eddy Simulation (LES), Detached-Eddy Simulation (DES, or hybrid RANS/LES methods), and Unsteady Reynolds-Averaged Navier-Stokes ...The separated turbulent flow around a circular cylinder is investigated using Large-Eddy Simulation (LES), Detached-Eddy Simulation (DES, or hybrid RANS/LES methods), and Unsteady Reynolds-Averaged Navier-Stokes (URANS). The purpose of this study is to examine some typical simulation approaches for the prediction of complex separated turbulent flow and to clarify the capability of applying these approaches to a typical case of the separated turbulent flow around a circular cylinder. Several turbulence models, i.e. dynamic Sub-grid Scale (SGS) model in LES, the DES-based Spalart-Allmaras (S-A) and κ-ω Shear-Stress- Transport (SST) models in DES, and the S-A and SST models in URANS, are used in the calculations. Some typical results, e.g., the mean pressure and drag coefficients, velocity profiles, Strouhal number, and Reynolds stresses, are obtained and compared with previous computational and experimental data. Based on our extensive calculations, we assess the capability and performance of these simulation approaches coupled with the relevant turbulence models to predict the separated turbulent flow.展开更多
AIM:To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation(ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS:The experime...AIM:To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation(ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS:The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco.The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy.The expression of fibronectin(FN) and laminin(LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS:Under light microscope,the alveolar exudation in the lung tissue was more frequently observed in the control group,while the alveolar space was fairly dry in the lung tissue of ICCBco group.Under electron microscope,more alveolar exudation in the lung tissue,and moremacrophages,alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group.In ICCBco group,fibers within the alveolar interspace slightly increased in some lung regions,and the structure of typeⅠepithelium,basement membrane and endodermis was complete,and no obvious exudation from the alveolar space,and novascular congestion could be observed.There was a positive or strong positive expression of FN and LN in the lung tissue of the control group,while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION:ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.展开更多
Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations.But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome ...Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations.But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear.This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus.Methods:The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed.Among these 67 cases,21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level Ⅱ-Ⅳ),while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0-Ⅰ).Clinical features,operation details,and pathology data were collected.Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus.Results:Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs.282.2 ± 101.9 min,t=4.685,P < 0.001),more surgical bleeding volume (1200 [325,2900] mL vs.500 [180,1000] mL,U =270.000,P =0.004),more surgical blood transfusion volume (800 [0,1400] mL vs.0 [0,800] mL,U =287.500,P =0.004),more plasma transfusion volume (0 [0,800] mL vs.0 [0,0] mL,U =319.000,P =0.004),higher percentage of open operative approach (76.2% vs.32.6%,x2 =11.015,P =0.001),higher percentage of IVC resection (33.3% vs.0%,x2 =17.122,P < 0.001),and higher percentage of post-operative complications (52.4% vs.19.6%,x2 =7.415,P =0.010) than patients with large tumors and low-level thrombus.In multivariate analysis,decreased hemoglobin (Hb)(odds ratio [OR]:0.956,95 % confidence interval [CI]:0.926-0.986,P =0.005) and non-sarcomatoid differentiation (OR:0.050,95% CI:0.004-0.664,P =0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with s展开更多
Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure ...Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.展开更多
AZ31 alloys were extruded by direct extrusion and bending–shear deformation(DEBS).The microstructure characteristic and texture evolution of DEBSed AZ31 sheets were investigated by electron backscattered diffraction(...AZ31 alloys were extruded by direct extrusion and bending–shear deformation(DEBS).The microstructure characteristic and texture evolution of DEBSed AZ31 sheets were investigated by electron backscattered diffraction(EBSD).It is found that DEBS technique could effectively refine grains and weaken texture.Besides,we also investigate how twinning affects dynamic recrystallization during hot extrusion.{10–12}extension twins can offer nucleation sites and enough energy to trigger dynamic recrystallization.Moreover,the character of direct extrusion and bending–shear die can lead to the activation of non-basal slip system and further dramatically weaken the basal texture of the microstructure with many preactivated basal slip systems.展开更多
文摘Background: The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen. Methods: A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration ofcorticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of tbllow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS). Results: The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P 0.021 ). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P 〈 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively. Conclusions: Addition of TMZ chemotherapy in the early break of the standard concomi
基金supported by the National Natural Science Foundation of China (Grant No. 90405007)the Hundred Talents Program of the Chinese Academy of SciencesProgram for Changjiang Scholars and Innovative Research Team in University.
文摘The separated turbulent flow around a circular cylinder is investigated using Large-Eddy Simulation (LES), Detached-Eddy Simulation (DES, or hybrid RANS/LES methods), and Unsteady Reynolds-Averaged Navier-Stokes (URANS). The purpose of this study is to examine some typical simulation approaches for the prediction of complex separated turbulent flow and to clarify the capability of applying these approaches to a typical case of the separated turbulent flow around a circular cylinder. Several turbulence models, i.e. dynamic Sub-grid Scale (SGS) model in LES, the DES-based Spalart-Allmaras (S-A) and κ-ω Shear-Stress- Transport (SST) models in DES, and the S-A and SST models in URANS, are used in the calculations. Some typical results, e.g., the mean pressure and drag coefficients, velocity profiles, Strouhal number, and Reynolds stresses, are obtained and compared with previous computational and experimental data. Based on our extensive calculations, we assess the capability and performance of these simulation approaches coupled with the relevant turbulence models to predict the separated turbulent flow.
基金Supported by National Natural Science Foundation of China,No.A30170920
文摘AIM:To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation(ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS:The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco.The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy.The expression of fibronectin(FN) and laminin(LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS:Under light microscope,the alveolar exudation in the lung tissue was more frequently observed in the control group,while the alveolar space was fairly dry in the lung tissue of ICCBco group.Under electron microscope,more alveolar exudation in the lung tissue,and moremacrophages,alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group.In ICCBco group,fibers within the alveolar interspace slightly increased in some lung regions,and the structure of typeⅠepithelium,basement membrane and endodermis was complete,and no obvious exudation from the alveolar space,and novascular congestion could be observed.There was a positive or strong positive expression of FN and LN in the lung tissue of the control group,while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION:ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.
基金grants from the National Key Research and Development Program of China (No. 2017YFA0205600 and No. 2016YFA0201400)the National Natural Science Foundation of China (NSFC-81771842).
文摘Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations.But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear.This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus.Methods:The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed.Among these 67 cases,21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level Ⅱ-Ⅳ),while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0-Ⅰ).Clinical features,operation details,and pathology data were collected.Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus.Results:Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs.282.2 ± 101.9 min,t=4.685,P < 0.001),more surgical bleeding volume (1200 [325,2900] mL vs.500 [180,1000] mL,U =270.000,P =0.004),more surgical blood transfusion volume (800 [0,1400] mL vs.0 [0,800] mL,U =287.500,P =0.004),more plasma transfusion volume (0 [0,800] mL vs.0 [0,0] mL,U =319.000,P =0.004),higher percentage of open operative approach (76.2% vs.32.6%,x2 =11.015,P =0.001),higher percentage of IVC resection (33.3% vs.0%,x2 =17.122,P < 0.001),and higher percentage of post-operative complications (52.4% vs.19.6%,x2 =7.415,P =0.010) than patients with large tumors and low-level thrombus.In multivariate analysis,decreased hemoglobin (Hb)(odds ratio [OR]:0.956,95 % confidence interval [CI]:0.926-0.986,P =0.005) and non-sarcomatoid differentiation (OR:0.050,95% CI:0.004-0.664,P =0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with s
基金the General Project of Chongqing Natural Science foundation of China(cstc2021jcyj-msxmX0877)the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau,2023MSXM054)the General Project of Chongqing Health Center for Women and Children(2020YJMS01 and 2021YJMS05).
文摘Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental arrest.Many studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains unknown.Whole-exome sequencing(WES)was performed to identify candidate mutations in couples with primary infertility.Sanger sequencing was used to validate the mutations.Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced.Assisted oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte activation.We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,p.R385Q.PN formation failure was observed during the ICSI cycle.However,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN formation.AOA after ICSI enabled normal fertilization,and all patients achieved successful pregnancies.These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy.Furthermore,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.
基金the National Natural Science Foundation of China(Nos.51704209,U1810208,U1810122)the Central Government Guided Local Science and Technology Development Projects,China(No.YDZJSX2021A010)+5 种基金the Projects of International Cooperation in Shanxi Province,China(Nos.201803D421086,201903D421076)Shanxi Province Patent Promotion Implementation Fund,China(No.20200718)the Technological Innovation Programs of Higher Education Institutions in Shanxi Province,China(No.201802034)Shanxi Province Scientific Facilities and Instruments Shared Service Platform of Magnesium-based Materials Electric Impulse Aided Forming,China(No.201805D141005)Science and Technology Major Project of Shanxi Province,China(Nos.20191102008,20191102007,20181101008)Yantai High-end Talent Introduction“Double Hundred Plan”,China(2021)。
基金supported partly by the National Natural Science Foundation of China (Grant Nos. 51505143 and 51728202)the Scientific Research Fund of Hunan Provincial Education Department (Grant No. 17B089)the financial supports from the China Postdoctoral Science Foundation (Grant Nos. 2016T90759 and 2014M562128)
文摘AZ31 alloys were extruded by direct extrusion and bending–shear deformation(DEBS).The microstructure characteristic and texture evolution of DEBSed AZ31 sheets were investigated by electron backscattered diffraction(EBSD).It is found that DEBS technique could effectively refine grains and weaken texture.Besides,we also investigate how twinning affects dynamic recrystallization during hot extrusion.{10–12}extension twins can offer nucleation sites and enough energy to trigger dynamic recrystallization.Moreover,the character of direct extrusion and bending–shear die can lead to the activation of non-basal slip system and further dramatically weaken the basal texture of the microstructure with many preactivated basal slip systems.
基金supported by the National Natural Science Foundation of China(Nos.52174362,51975207)Natural Science Foundation of Hunan Province,China(No.2023JJ10020)+1 种基金Xiangtan Special Project for Building a National Innovative City,China(No.CG-YB20221043)Yancheng“Talent Plan of Yellow Sea Pearl”for Leading Talent Project,China。
基金partly supported by the National Natural Science Foundation of China (Nos. 52174362, 51975207)the Xiangtan Special Project for Building a National Innovative City,China (No. CG-YB20221043)the Yancheng “Talent Plan of Yellow Sea Pearl” for Leading Talent Project,China。