Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
BACKGROUND Controversy exists as to the optimal treatment approach for ostial left anterior descending(LAD)or ostial left circumflex artery(LCx)lesions.Drug-coated balloons(DCB)may overcome some of the limitations of ...BACKGROUND Controversy exists as to the optimal treatment approach for ostial left anterior descending(LAD)or ostial left circumflex artery(LCx)lesions.Drug-coated balloons(DCB)may overcome some of the limitations of drug-eluting stents(DES).Therefore,we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions,and compared it with the conventional DES-only strategy.METHODS We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment.They were categorized into two groups based on their treatment approach:the DCB group and the DES group.The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies,whereas the DES group utilized crossover or precise stenting techniques.Two-year target lesion revascularization was the primary endpoint,while the rates of major adverse cardiovascular events,cardiac death,target vessel myocardial infarction,and vessel thrombosis were the secondary endpoints.Using propensity score matching,we assembled a cohort with comparable baseline characteristics.To ensure result analysis reliability,we conducted sensitivity analyses,including interaction,and stratified analyses.RESULTS Among the 397 eligible patients,6.25%of patients who were planned to undergo DCB underwent DES.A total of 108 patients in each group had comparable propensity scores and were included in the analysis.Two-year target lesion revascularization occurred in 5 patients(4.90%)and 16 patients(16.33%)in the DCB group and the DES group,respectively(odds ratio=0.264,95%CI:0.093–0.752,P=0.008).Compared with the DES group,the DCB group demonstrated a lower major adverse cardiovascular events rate(7.84%vs.19.39%,P=0.017).However,differences with regard to cardiac death,non-periprocedural target vessel myocardial infarction,and definite or probable vessel thrombosis between the groups were non-significant.CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx.Nevertheless,a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.展开更多
Objective： The aim of this study was to evaluate the safety and efficiency of enucleation（EU） for proximal pancreatic non-invasive neoplasms.Methods： Patients with solitary non-invasive neoplasms in the proximal p...Objective： The aim of this study was to evaluate the safety and efficiency of enucleation（EU） for proximal pancreatic non-invasive neoplasms.Methods： Patients with solitary non-invasive neoplasms in the proximal pancreas from January 1998 to April 2014 at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China were included.Different operations and outcomes were analyzed.Results： A total of 123 patients were enrolled.Forty patients（32.5%） underwent EU including 18 patients who had tumors close to the main pancreatic duct（MPD）.Sixty-one patients（49.6%） had pancreaticoduodenectomy（PD） performed and 22（17.9%） underwent central pancreatectomy（CP）.Pathological outcomes included neuroendocrine tumors, cystic lesions, and solid pseudopapillary tumors.Operation time, intra-operative blood loss, and duration of hospital stay were significantly reduced in the EU group.PD was associated with the greatest complication rate（55.7%）, followed by EU（50%） and CP（40.9%）, though the pancreatic fistula rate after EU was the highest（50%）, especially in patients with tumors larger than 3 cm and tumors close to the MPD.EU had advantages in the preservation of pancreatic parenchyma and endocrine and exocrine function.Conclusions： EU can be carried out safely and effectively for tumors in the proximal pancreas with improved outcomes compared with standard resections, even if the tumor is larger than 3 cm and close to the MPD.展开更多
Insect ryanodine receptors(RyRs)are the targets of diamide insecticides.Two point mutations G4946E and I4790M(numbering according to Plutella xylostella,PxRyR)in the transmembrane domain of the insect RyRs associated ...Insect ryanodine receptors(RyRs)are the targets of diamide insecticides.Two point mutations G4946E and I4790M(numbering according to Plutella xylostella,PxRyR)in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests,P.xylostella,Tuta absoluta and Chilo suppressalis.In this study,we identified one of the known RyR target site resistance mutations(I4790M)in a field-collected population of Spodoptera exigua.The field-collected WF population of S.exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain.Sequencing the transmembrane domains of S.exigua RyR(SeRyR)revealed that the resistant WF strain was homozygous for the 14743M mutation(corresponding to I4790M in PxRyR),whereas the G4900E allele(corresponding to G4946E of PxRyR)was not detected.The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S,followed by three rounds of backcrossing with WH-S.The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94%of its genetic background with that of the recipient WH-S strain.Compared with WH-S,the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole(21 fold),cyantraniliprole(25 fold)and flubendiamide(22 fold),suggesting that the I4743M mutation confers medium levels of resistance to all three diamides.Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait.Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S.exigua.展开更多
Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities,but effective clinical interventions for restoring neurological functions have yet to be developed.In early ...Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities,but effective clinical interventions for restoring neurological functions have yet to be developed.In early spinal cord development,neural progenitors of the motor neuron(pMN)domain,defined by the expression of oligodendrocyte transcription factor 2(OLIG2),in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes.Given their differentiation potential,pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury.However,fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging.In this study,based on chemical screening,we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells.More importantly,these OLIG2+pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly.Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.展开更多
The evolutions of nano-twins and martensitic transformation in 316L austenitic stainless steel during large tensile deformation were studied by electron backscatter diffraction(EBSD)technology and transmission electro...The evolutions of nano-twins and martensitic transformation in 316L austenitic stainless steel during large tensile deformation were studied by electron backscatter diffraction(EBSD)technology and transmission electron microscopy(TEM)in detail.The results show that due to the low stacking fault energy of the steel,phase transformation induced plasticity(TRIP)and twinning induced plasticity(TWIP)coexist during the tensile deformation.The deformation firstly induces the formation of deformation twins,and dislocation pile-up is caused by the reduction of the dislocation mean free path(MFP)or grain refinement due to the twin boundaries,which further induces the martensitic transformation.With the increase of tensile deformation,a large number of nano-twins andα’-martensite appear,and the width of nano-twins decreases gradually,meanwhile the frequency of the intersecting deformation twins increases.The martensitic transformation can be divided into two types:γ-austenite→α’-martensite andγ-austenite→ε-martensite.α’-martensite is mainly distributed near the twin boundaries,especially at the intersection of twins,whileε-martensite and stacking faults exist in the form of transition products between the twins and the matrix.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
基金supported by the Medical Science and Technique Research Plan of He’nan Province(Provincial and Ministerial Co-construction Project)(SB201901027).
文摘BACKGROUND Controversy exists as to the optimal treatment approach for ostial left anterior descending(LAD)or ostial left circumflex artery(LCx)lesions.Drug-coated balloons(DCB)may overcome some of the limitations of drug-eluting stents(DES).Therefore,we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions,and compared it with the conventional DES-only strategy.METHODS We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment.They were categorized into two groups based on their treatment approach:the DCB group and the DES group.The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies,whereas the DES group utilized crossover or precise stenting techniques.Two-year target lesion revascularization was the primary endpoint,while the rates of major adverse cardiovascular events,cardiac death,target vessel myocardial infarction,and vessel thrombosis were the secondary endpoints.Using propensity score matching,we assembled a cohort with comparable baseline characteristics.To ensure result analysis reliability,we conducted sensitivity analyses,including interaction,and stratified analyses.RESULTS Among the 397 eligible patients,6.25%of patients who were planned to undergo DCB underwent DES.A total of 108 patients in each group had comparable propensity scores and were included in the analysis.Two-year target lesion revascularization occurred in 5 patients(4.90%)and 16 patients(16.33%)in the DCB group and the DES group,respectively(odds ratio=0.264,95%CI:0.093–0.752,P=0.008).Compared with the DES group,the DCB group demonstrated a lower major adverse cardiovascular events rate(7.84%vs.19.39%,P=0.017).However,differences with regard to cardiac death,non-periprocedural target vessel myocardial infarction,and definite or probable vessel thrombosis between the groups were non-significant.CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx.Nevertheless,a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.
基金Project supported by the National Natural Science Foundation of China(Nos.30672072 and 30872531)the Foundation of Science and Technology Department of Zhejiang Province,China(Nos.2014C 33187)the National High-Tech R&D Program(863)of China(No.2007AA02Z476)
文摘Objective： The aim of this study was to evaluate the safety and efficiency of enucleation（EU） for proximal pancreatic non-invasive neoplasms.Methods： Patients with solitary non-invasive neoplasms in the proximal pancreas from January 1998 to April 2014 at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China were included.Different operations and outcomes were analyzed.Results： A total of 123 patients were enrolled.Forty patients（32.5%） underwent EU including 18 patients who had tumors close to the main pancreatic duct（MPD）.Sixty-one patients（49.6%） had pancreaticoduodenectomy（PD） performed and 22（17.9%） underwent central pancreatectomy（CP）.Pathological outcomes included neuroendocrine tumors, cystic lesions, and solid pseudopapillary tumors.Operation time, intra-operative blood loss, and duration of hospital stay were significantly reduced in the EU group.PD was associated with the greatest complication rate（55.7%）, followed by EU（50%） and CP（40.9%）, though the pancreatic fistula rate after EU was the highest（50%）, especially in patients with tumors larger than 3 cm and tumors close to the MPD.EU had advantages in the preservation of pancreatic parenchyma and endocrine and exocrine function.Conclusions： EU can be carried out safely and effectively for tumors in the proximal pancreas with improved outcomes compared with standard resections, even if the tumor is larger than 3 cm and close to the MPD.
基金This work was funded by a grant from the Ministry of Agriculture and Rural Affairs(MARA)of China(No.2016YFD0200500).
文摘Insect ryanodine receptors(RyRs)are the targets of diamide insecticides.Two point mutations G4946E and I4790M(numbering according to Plutella xylostella,PxRyR)in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests,P.xylostella,Tuta absoluta and Chilo suppressalis.In this study,we identified one of the known RyR target site resistance mutations(I4790M)in a field-collected population of Spodoptera exigua.The field-collected WF population of S.exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain.Sequencing the transmembrane domains of S.exigua RyR(SeRyR)revealed that the resistant WF strain was homozygous for the 14743M mutation(corresponding to I4790M in PxRyR),whereas the G4900E allele(corresponding to G4946E of PxRyR)was not detected.The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S,followed by three rounds of backcrossing with WH-S.The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94%of its genetic background with that of the recipient WH-S strain.Compared with WH-S,the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole(21 fold),cyantraniliprole(25 fold)and flubendiamide(22 fold),suggesting that the I4743M mutation confers medium levels of resistance to all three diamides.Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait.Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S.exigua.
基金unding This study was supported by grants from the National Key R&D Program of China(2018YFA0107200 and 2020YFA0113101)the National Natural Science Foundation of China(81571094,81322016,32070866,and 31771643)+4 种基金the Program of Shanghai Academic Research Leader(17XD1404800)the Biotechnology and Biological Sciences Research Council(BB/S000844/1 and BB/S008934/1)Newton Advanced Fellowship(AMS-NAF1-Li),Shanghai Science and Technology Committee(19JC1413200)the program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(1710000009)the Shanghai Key Laboratory of Reproductive Medicine.
文摘Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities,but effective clinical interventions for restoring neurological functions have yet to be developed.In early spinal cord development,neural progenitors of the motor neuron(pMN)domain,defined by the expression of oligodendrocyte transcription factor 2(OLIG2),in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes.Given their differentiation potential,pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury.However,fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging.In this study,based on chemical screening,we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells.More importantly,these OLIG2+pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly.Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.
基金supported by the Natural Science Foundation of Shaanxi Province,China(No.2021JM-061).
文摘The evolutions of nano-twins and martensitic transformation in 316L austenitic stainless steel during large tensile deformation were studied by electron backscatter diffraction(EBSD)technology and transmission electron microscopy(TEM)in detail.The results show that due to the low stacking fault energy of the steel,phase transformation induced plasticity(TRIP)and twinning induced plasticity(TWIP)coexist during the tensile deformation.The deformation firstly induces the formation of deformation twins,and dislocation pile-up is caused by the reduction of the dislocation mean free path(MFP)or grain refinement due to the twin boundaries,which further induces the martensitic transformation.With the increase of tensile deformation,a large number of nano-twins andα’-martensite appear,and the width of nano-twins decreases gradually,meanwhile the frequency of the intersecting deformation twins increases.The martensitic transformation can be divided into two types:γ-austenite→α’-martensite andγ-austenite→ε-martensite.α’-martensite is mainly distributed near the twin boundaries,especially at the intersection of twins,whileε-martensite and stacking faults exist in the form of transition products between the twins and the matrix.
