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 examine the determinants of maternal-neonatal transmission of hepatitis B virus(HBV) METHODS:A nested case-control study was conducted in Changsha,Hunan,People's Republic of China from January 1,2005 to Sep...AIM:To examine the determinants of maternal-neonatal transmission of hepatitis B virus(HBV) METHODS:A nested case-control study was conducted in Changsha,Hunan,People's Republic of China from January 1,2005 to September 31,2006 To avoid potential maternal blood contamination,we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV infection status of the newborn For each HBsAg-positive infant,one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth(same),gender(same),and date of birth(within 1 mo) A faceto-face interview was conducted to collect clinical and epidemiological data Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmission of HBV RESULTS:A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis Maternal first-degree family history of HBV infection,intrahepatic cholestasis,and premature rupture of membranes were risk factors for perinatal transmission of HBV,whereas systematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV,after adjustment for potential confounding factors CONCLUSION:For HBsAg-positive mothers,systematic treatment,HBV immunoglobulin administration,and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.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 Hunan Ministry of Science and Technology,No.06FJ3177,China
文摘AIM:To examine the determinants of maternal-neonatal transmission of hepatitis B virus(HBV) METHODS:A nested case-control study was conducted in Changsha,Hunan,People's Republic of China from January 1,2005 to September 31,2006 To avoid potential maternal blood contamination,we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV infection status of the newborn For each HBsAg-positive infant,one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth(same),gender(same),and date of birth(within 1 mo) A faceto-face interview was conducted to collect clinical and epidemiological data Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmission of HBV RESULTS:A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis Maternal first-degree family history of HBV infection,intrahepatic cholestasis,and premature rupture of membranes were risk factors for perinatal transmission of HBV,whereas systematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV,after adjustment for potential confounding factors CONCLUSION:For HBsAg-positive mothers,systematic treatment,HBV immunoglobulin administration,and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.
