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
Drill string will sustain large uplift force during the shut-in period after gas overflow in an ultra-deep well, and in serious case, it will run out of the wellhead. A calculation model of uplift force was establishe...Drill string will sustain large uplift force during the shut-in period after gas overflow in an ultra-deep well, and in serious case, it will run out of the wellhead. A calculation model of uplift force was established to analyze dynamic change characteristics of the uplift force of drill string during the shut-in period, and then a management procedure for the uplift risk during the shut-in period after gas overflow in the ultra-deep well was formed. Cross section method and pressure area method were used to analyze the force on drill string after shut-in of well, it was found that the source of uplift force was the "fictitious force" caused by the hydrostatic pressure in the well. When the fictitious force is in the opposite direction to the gravity, it is the uplift force. By adopting the theory of annular multiphase flow, considering the effects of wellbore afterflow and gas slippage, the dynamic change of the pressure and fluid in the wellbore and the uplift force of drill string during the shut-in period were analyzed. The magnitude and direction of uplift force are related to the length of drill string in the wellbore and shut-in time, and there is the risk of uplift of drill string when the length of drill string in the wellbore is smaller than the critical drill string length or the shut in time exceeds the critical shut in time. A set of treatment method and process to prevent the uplift of drill string is advanced during the shut-in period after overflow in the ultra-deep well, which makes the risk management of the drill string uplift in the ultra-deep well more rigorous and scientific.展开更多
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
AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Thr...AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Three STL children,aged 3,7,and 11y,received RLRL therapy throughout the follow-up period of 17,3,and 6mo,respectively after exclusion of fundus anomalies.Data on best-corrected visual acuity(BCVA),intraocular pressure,cycloplegic subjective refraction,ocular biometrics,scanning laser ophthalmoscope,optical coherence tomography,genetic testing,systemic disease history,and family history were recorded.RESULTS:At the initiation of the RLRL therapy,the spherical equivalent(SE)of 6 eyes from 3 patients ranged from-3.75 to-20.38 D,axial length(AL)were from 23.88 to 30.68 mm,and BCVA were from 0.4 to 1.0(decimal notation).Myopia progression of all six eyes slowed down after RLRL therapy.AL in five out of the six eyes shortened-0.07 to-0.63 mm.No side effects were observed.CONCLUSION:Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.展开更多
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.
基金Supported by China National Science and Technology Major Project(2016ZX05020-006)
文摘Drill string will sustain large uplift force during the shut-in period after gas overflow in an ultra-deep well, and in serious case, it will run out of the wellhead. A calculation model of uplift force was established to analyze dynamic change characteristics of the uplift force of drill string during the shut-in period, and then a management procedure for the uplift risk during the shut-in period after gas overflow in the ultra-deep well was formed. Cross section method and pressure area method were used to analyze the force on drill string after shut-in of well, it was found that the source of uplift force was the "fictitious force" caused by the hydrostatic pressure in the well. When the fictitious force is in the opposite direction to the gravity, it is the uplift force. By adopting the theory of annular multiphase flow, considering the effects of wellbore afterflow and gas slippage, the dynamic change of the pressure and fluid in the wellbore and the uplift force of drill string during the shut-in period were analyzed. The magnitude and direction of uplift force are related to the length of drill string in the wellbore and shut-in time, and there is the risk of uplift of drill string when the length of drill string in the wellbore is smaller than the critical drill string length or the shut in time exceeds the critical shut in time. A set of treatment method and process to prevent the uplift of drill string is advanced during the shut-in period after overflow in the ultra-deep well, which makes the risk management of the drill string uplift in the ultra-deep well more rigorous and scientific.
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.
文摘AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Three STL children,aged 3,7,and 11y,received RLRL therapy throughout the follow-up period of 17,3,and 6mo,respectively after exclusion of fundus anomalies.Data on best-corrected visual acuity(BCVA),intraocular pressure,cycloplegic subjective refraction,ocular biometrics,scanning laser ophthalmoscope,optical coherence tomography,genetic testing,systemic disease history,and family history were recorded.RESULTS:At the initiation of the RLRL therapy,the spherical equivalent(SE)of 6 eyes from 3 patients ranged from-3.75 to-20.38 D,axial length(AL)were from 23.88 to 30.68 mm,and BCVA were from 0.4 to 1.0(decimal notation).Myopia progression of all six eyes slowed down after RLRL therapy.AL in five out of the six eyes shortened-0.07 to-0.63 mm.No side effects were observed.CONCLUSION:Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.