Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H ...Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.展开更多
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "fac...Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.展开更多
Primary squamous cell carcinoma of the rectum is a rare malignancy,and the discrete dual lesions of rectum are even rarer.There is currently no effective and satisfactory treatment for this disease.Here we report a ca...Primary squamous cell carcinoma of the rectum is a rare malignancy,and the discrete dual lesions of rectum are even rarer.There is currently no effective and satisfactory treatment for this disease.Here we report a case of an elderly female with bi-primary squamous cell carcinoma of the rectum treated with radical resection and radiotherapy.The patient is still alive 43mo after the initial curative resection of the tumor.We suggest that surgery as the primary treatment followed by concomitant radiotherapy may be an effective protocol for elderly patients with rectal squamous cell carcinoma.展开更多
BACKGROUND Azygos vein aneurysms are extremely rare,and their pathogenesis is not clear.The overwhelming majority of patients have no obvious clinical symptoms and are found to have the disease by physical examination...BACKGROUND Azygos vein aneurysms are extremely rare,and their pathogenesis is not clear.The overwhelming majority of patients have no obvious clinical symptoms and are found to have the disease by physical examination or by chance.There are few reports on the diagnosis of and treatment strategy for this disease.Moreover,the choice of therapeutic schedule and the treatment window are controversial.CASE SUMMARY We report a case of azygos vein arch aneurysm in a 53-year-old woman.The patient had symptoms of back pain,chest tightness,and choking.Enhanced chest computed tomography showed a soft-tissue mass in the right posterior mediastinum,which was connected to the superior vena cava.The enhancement degree in the venous phase was the same as that of the superior vena cava.The patient received video-assisted thoracoscopic surgery.After the operation,her back pain disappeared,and her dysphagia and chest tightness were also significantly relieved.The postoperative pathology confirmed hemangioma.The patient was discharged on the seventh day after surgery without any complications.CONCLUSION Some patients with hemangioma of the azygos vein arch may experience dysphagia and chest tightness caused by the tumor compressing the esophagus and trachea.Enhanced computed tomography scanning is vital for the diagnosis of azygos vein aneurysms.In addition,despite the difficulty and risk of surgery,thoracoscopic surgery for azygos vein aneurysms is completely feasible.展开更多
Objective:To evaluate the efficacy and safety of Xuesaitong Injection in the treatment of angina pectoris.Methods:CNKI and WAN were retrieved Fang,VIP,CBMdisc,PubMed and Cochrane libraries published a randomized contr...Objective:To evaluate the efficacy and safety of Xuesaitong Injection in the treatment of angina pectoris.Methods:CNKI and WAN were retrieved Fang,VIP,CBMdisc,PubMed and Cochrane libraries published a randomized controlled trial of Xuesaitong Injection in the treatment of angina pectoris of coronary heart disease from the beginning of the establishment of the database to January 2020.29 cases were finally included in the study through layer by layer selection.The total sample size was 2560 cases,including 1307 cases in the experimental group and 1253 cases in the control group.The data collected were meta analyzed by Revman 5.3 software.Results:on the basis of routine western medicine treatment,Xuesaitong injection was added in the clinical comprehensive effective rate([RR=1.31;95%CI(1.25,1.39)]),angina symptom improvement rate([RR=1.16;95%CI(1.07,1.26)]),ECG improvement rate([RR=1.25;95%CI(1.14,1.38)]),angina attack times([RR=-2.49;95%CI(-3.27,-1.70)]);fibrinogen([MD=-0.61;95%CI(-0.77,-0.45)]),plasma(specific)viscosity([MD=-0.19;95%CI(-0.22,-0.16)]),hematocrit([MD=-0.04;95%CI(-0.05,-0.03)])and other aspects were superior to the conventional treatment of Western medicine,the difference was statistically significant.Safety aspect:the reported adverse reactions were mild and tolerable events such as headache,dizziness,flush,etc.,no serious adverse events,and no separation from the report was found.Conclusion:on the basis of conventional western medicine,Xuesaitong injection can effectively improve the clinical efficacy,and has a high safety.However,due to the low quality of the included study and the small sample size,there is a potential bias in the study;therefore,the application and promotion of the research conclusions need to be cautious,and need to be further verified by more large sample,multicenter,double-blind clinical randomized controlled trials.展开更多
Precise modulation of the magnetic anisotropy of metal ions remains highly important for the development of high–performance single-molecule magnets(SMMs).We herein reported the synthetic,structural,spectral,magnetic...Precise modulation of the magnetic anisotropy of metal ions remains highly important for the development of high–performance single-molecule magnets(SMMs).We herein reported the synthetic,structural,spectral,magnetic,and computational studies on four mononuclear Co^(Ⅱ) complexes in a distorted octahedral environment.The change of the organosulfonate anions triggers significant modification of the distorted octahedral CoN6 coordination sphere,which enables us to tackle the influence of the structural distortion on the magnetic anisotropy in these complexes.Magnetic measurements revealed that the four complexes possess easy–plane magnetic anisotropy with large and positive zero-field splitting parameters,which decrease with the increasing distortion of the pseudo–octahedral Co^(Ⅱ) coordination geometry.This correlation was further confirmed by high–frequency/–field EPR(HF–EPR)spectra and theoretical calculations.Dynamic magnetic susceptibility measurements indicate that these complexes both exhibit slow magnetic relaxation under an external dc field,indicating the field-induced single-ion magnets(SIMs)of the four complexes.These results indicate that structural distortion plays an important role in the magnetic anisotropy of CoⅡcomplexes and should be carefully considered in the design of molecular complexes with high magnetic anisotropy.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos.81874006,82172399,81902222,82060395,81902277,82072504,82000845)the Hunan Province Natural Science Foundation of China (Grant Nos.2020JJ4928,2020JJ4897,2021JJ30038,2021JJ40492)the Independent Exploration and Innovation Project of Central South University (Grant Nos.2020zzts255)。
文摘Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
基金supported by the Changsha Municipal Natural Science Foundation,China,(No.kq2202233)the Science and Technology Program of Guangdong Forestry Administration,China(No.2020-KYXM-08)+2 种基金the Major Science and Technology Program for Water Pollution Control and Treatment,China(No.2017ZX07101003)the National Key Research and Development Project of China(No.2019YFC1804800)the Pearl River S&T Nova Program of Guangzhou,China(No.201710010065)。
基金funded by the National Key Research and Development Project (No.2019YFC1804800)Key R&D Program of Shaanxi Province,China (No.2019SF-253)+3 种基金the Fundamental Research Funds for the Central Universities,China (No.300102291504)the Pearl River S&T Nova Program of Guangzhou,China (No.201710010065)the Science and Technology Program of Guangdong Forestry Administration,China (No.2020-KYXM-08)the Key Laboratory of Resource Chemistry,Ministry of Education,China (No.KLRC_ME2102)。
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
基金supported by the National Natural Science Foundation of China (Grant nos. 81522012, 81702237, 81670807, 81871822, 81801395, 81600699, 81701383, and 81802138)the Thousand Youth Talents Plan of China (Grant no. D1119003)+8 种基金the Medicine and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences (Grant no. 2018-I2M-HL-024)the High Level Talent Gathering Project of Hunan Province (Grant nos. 2017XK2039, and 2018RS3029)the Innovation Driven Project of Central South University (Grant nos. 2016CX028,2019CX014, and 2018CX029)the Youth Foundation of Xiangya Hospital in Central South University (Grant no. 2016Q10)the Hunan Provincial Innovation Foundation for Postgraduate (Grant no. CX2018B045)the Fundamental Research Funds for the Central Universities of Central South University (Grant nos. 2017zzts211 and 2018zzts895)the Hunan Province Natural Science Foundation of China (Grant no. 2017JJ3501)the China Postdoctoral Science Foundation (Grant nos. 2017M612596, 2017M622614, and 2018M632998)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province (Grant no. 2016A030306051)
文摘Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.
文摘Primary squamous cell carcinoma of the rectum is a rare malignancy,and the discrete dual lesions of rectum are even rarer.There is currently no effective and satisfactory treatment for this disease.Here we report a case of an elderly female with bi-primary squamous cell carcinoma of the rectum treated with radical resection and radiotherapy.The patient is still alive 43mo after the initial curative resection of the tumor.We suggest that surgery as the primary treatment followed by concomitant radiotherapy may be an effective protocol for elderly patients with rectal squamous cell carcinoma.
基金Science and Technology Development Plan Project of Jilin Province,China,No.JJKH20201060KJ.
文摘BACKGROUND Azygos vein aneurysms are extremely rare,and their pathogenesis is not clear.The overwhelming majority of patients have no obvious clinical symptoms and are found to have the disease by physical examination or by chance.There are few reports on the diagnosis of and treatment strategy for this disease.Moreover,the choice of therapeutic schedule and the treatment window are controversial.CASE SUMMARY We report a case of azygos vein arch aneurysm in a 53-year-old woman.The patient had symptoms of back pain,chest tightness,and choking.Enhanced chest computed tomography showed a soft-tissue mass in the right posterior mediastinum,which was connected to the superior vena cava.The enhancement degree in the venous phase was the same as that of the superior vena cava.The patient received video-assisted thoracoscopic surgery.After the operation,her back pain disappeared,and her dysphagia and chest tightness were also significantly relieved.The postoperative pathology confirmed hemangioma.The patient was discharged on the seventh day after surgery without any complications.CONCLUSION Some patients with hemangioma of the azygos vein arch may experience dysphagia and chest tightness caused by the tumor compressing the esophagus and trachea.Enhanced computed tomography scanning is vital for the diagnosis of azygos vein aneurysms.In addition,despite the difficulty and risk of surgery,thoracoscopic surgery for azygos vein aneurysms is completely feasible.
基金“Major new drug creation” of 13th five-year science and technology major project (No.2018ZX09734-002)。
文摘Objective:To evaluate the efficacy and safety of Xuesaitong Injection in the treatment of angina pectoris.Methods:CNKI and WAN were retrieved Fang,VIP,CBMdisc,PubMed and Cochrane libraries published a randomized controlled trial of Xuesaitong Injection in the treatment of angina pectoris of coronary heart disease from the beginning of the establishment of the database to January 2020.29 cases were finally included in the study through layer by layer selection.The total sample size was 2560 cases,including 1307 cases in the experimental group and 1253 cases in the control group.The data collected were meta analyzed by Revman 5.3 software.Results:on the basis of routine western medicine treatment,Xuesaitong injection was added in the clinical comprehensive effective rate([RR=1.31;95%CI(1.25,1.39)]),angina symptom improvement rate([RR=1.16;95%CI(1.07,1.26)]),ECG improvement rate([RR=1.25;95%CI(1.14,1.38)]),angina attack times([RR=-2.49;95%CI(-3.27,-1.70)]);fibrinogen([MD=-0.61;95%CI(-0.77,-0.45)]),plasma(specific)viscosity([MD=-0.19;95%CI(-0.22,-0.16)]),hematocrit([MD=-0.04;95%CI(-0.05,-0.03)])and other aspects were superior to the conventional treatment of Western medicine,the difference was statistically significant.Safety aspect:the reported adverse reactions were mild and tolerable events such as headache,dizziness,flush,etc.,no serious adverse events,and no separation from the report was found.Conclusion:on the basis of conventional western medicine,Xuesaitong injection can effectively improve the clinical efficacy,and has a high safety.However,due to the low quality of the included study and the small sample size,there is a potential bias in the study;therefore,the application and promotion of the research conclusions need to be cautious,and need to be further verified by more large sample,multicenter,double-blind clinical randomized controlled trials.
基金supported by the National Key R&D Program of China(No.2018YFA0306002)the National Natural Science Foundation of China(Nos.21973039,21973046)+1 种基金D.S.thanks the Huanggang Normal University for a start-up fund(No.2042021033)the Open Foundation of State Key Laboratory of Coordination Chemistry(No.SKLCC2208).
文摘Precise modulation of the magnetic anisotropy of metal ions remains highly important for the development of high–performance single-molecule magnets(SMMs).We herein reported the synthetic,structural,spectral,magnetic,and computational studies on four mononuclear Co^(Ⅱ) complexes in a distorted octahedral environment.The change of the organosulfonate anions triggers significant modification of the distorted octahedral CoN6 coordination sphere,which enables us to tackle the influence of the structural distortion on the magnetic anisotropy in these complexes.Magnetic measurements revealed that the four complexes possess easy–plane magnetic anisotropy with large and positive zero-field splitting parameters,which decrease with the increasing distortion of the pseudo–octahedral Co^(Ⅱ) coordination geometry.This correlation was further confirmed by high–frequency/–field EPR(HF–EPR)spectra and theoretical calculations.Dynamic magnetic susceptibility measurements indicate that these complexes both exhibit slow magnetic relaxation under an external dc field,indicating the field-induced single-ion magnets(SIMs)of the four complexes.These results indicate that structural distortion plays an important role in the magnetic anisotropy of CoⅡcomplexes and should be carefully considered in the design of molecular complexes with high magnetic anisotropy.
