The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Objective:To explore the characters of CDU imaging anatomy and results of clinical application of perforating branch of median cubital vein, and to find the evidence of utilizing perforating vein to establish high level hemodialysis access.Methods:From November, 2016 to October, 2019, 150 median cubital veins in 75 persons were observed by CDU. And the inner diameter and length of the perforating branch were measured Perforating branches of median cubital vein were categorized with ultrasonic imaging anatomy. Thirty-eight chronic kidney failure patients who can not build forearm fistulas were operated by end-to-side anastomosis between perforating branch vein and brachial artery to build hemodialysis access. The blood flow of fisultas was measured,the mature period of fisultas was recorded. The length of available vessels of fisultas was measured and the long-term utilization rate of fisultas was counted.Results:Perforating branch of median cubital vein was always located in a little below elbow near brachial artery, the rate of occurrence was 94.0%. It was sent out at intersection of veins. There were 4 types of perforating vein in image-anatomy. There was no significant difference in vessel length and vessel inner diameter between different types ( P>0.05) ; All the 38 patients with mature fistulas could meet the needs of hemodialysis. The available vascular length of fistulas in type I and type II patients was better than that in type III ( P<0.01), and the long-term utilization rates of fistulas in type I, type II and type III were 84.6%, 85.7% and 72.7%, respectively. There was no significant difference in blood flow and mature period between different types ( P>0.05) . Conclusion:It is most safe and reliable to use the type I and type II of perforating branch of median cubital vein to make the high level fistulas , which can provide a safe and efficient hemodialysis access for the patients with forearm vascular drain, elderly diabetes patients and difficult fistulas with repeatedly thrombosis.

Objective     To analyze the clinical efficacy and safety of endostar or carboplatin combined with endostar intracavitary perfusion in the treatment of malignant serous cavity effusion. Methods     We retrospectively reviewed the clinical data of 78 cancer patients with malignant serous cavity effusion who received paracentesis and intracavitary endostar, or carboplatin combined with endostar in Shengjing Hospital of China Medical University between November 2011 and November 2016. There were 42 males and 36 females at a median age of 62 years ranging from 17 to 78 years. According to treatment methods, 78 patients were divided into two groups, in which 33 patients received intracavitary endostar combined with carboplatin (a combination group, 15 males and 18 females at a median age of 56 years ranging from 17 to 66 years), and 45 patients received intracavitary endostar (an endostar group, 27 males and 18 females at a median age of 63 years ranging from 38 to 78 years). The efficacy and safety of two methods were analyzed and compared. Results     The response rate in the combination group was 75.8%, which was higher than that in the endostar group (60.0%, P=0.035). In quality of life improvement, there was no statistical difference between the two groups (P=0.113). The incidence of fatigue, myelosuppression and gastrointestinal reactions in the endostar group was significantly lower than that of the combination group (P=0.006, 0.000 and 0.017, respectively). Analysis of long-term efficacy revealed that the median time to progress (TTP) in the combination group and endostar group was 171 days and 143 days, respectively (P=0.030). Conclusion     Intracavitary infusion of endostar alone, or carboplatin combined with  endostar is effective and tolerable for controlling malignant serous cavity effusion. But for the patients with poor physical state who can not tolerant platinum perfusion, intracavitary infusion of endostar alone can be adopted to control malignant serous cavity effusion.

Objective The aim of this study was to retrospectively review the efficacy and safety of treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC).Methods A total of 98 patients treated in our hospital between January 2010 and December 2015 were enrolled in this study.Patients were divided into three groups:the thoracic radiotherapy (TRT) alone,concurrent chemoradiotherapy,and sequential chemoradiotherapy groups.The progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method,and compared with the log-rank/Breslow test.The prognostic factors were analyzed using the Kaplan-Meier and Cox multivariate proportional hazards models.Results The median PFS in the concurrent therapy group was longer than that in the TRT alone group (P ＜ 0.05).The median OS was improved in patients treated with concurrent or sequential therapy than in the TRT alone group (P ＜ 0.05).N stage,chemotherapy regimens,and radiotherapy modalities were independent prognostic factors of PFS in all patients (P ＜0.05).Similarly,N stage was an independent prognostic factor of OS in all patients (P ＜ 0.05).Overall,the treatment was deemed safe.The occurrence of hematotoxicity related to Karnofsky performance score (KPS) and chemotherapy regimens (P ＜ 0.05).Conclusion Patients with a lower N stage who received cisplatin-based double chemoradiotherapy demonstrated improved survival rates.Survival was significantly improved in LA-NSCLC patients treated with concurrent or sequential therapies compared with TRT alone.Overall,the treatment is safe.KPS and chemotherapy combination regimens may increase the occurrence of hematotoxicity.

Objective To assess whether it have difference between mannitol combined with glycerin fructose and only use mannitol for the treatment of cerebral hemorrhage ,which provides relevant evidence‐based basis for guiding clinical treatment of cerebral hemorrhage .Methods We used literature retrieval through to the China national knowledge internet (CNKI) ,China biolo‐gy medicine disc ,VIP Chinese periodical database ,Wanfang data knowledge service platform and manual retrieval ,and formulate the inclusion and exclusion to screening literature ;and using the Jadad quality evaluation method to evaluate literature which had been included ,heterogeneity inspection at the same time .If the effect of multiple resulted ,we used fixed effect model ;on the other hand , used a random effects model .Results Mannitol combined glycerol fructose significantly improved symptoms and nervous function in patients with cerebral hemorrhage ,and the difference was statistically significant (RR=1 .12 ,95% CI:1 .03 -1 .22 ,P<0 .01);mannitol combined glycerol fructose significantly decreasd impaired renal function and complications (RR=0 .34 ,95% CI:0 .25-0 . 47 ,P<0 .01);mannitol combined glycerol fructose significantly decreasd severe unbalance of electrolyte after taking the medicine (RR=0 .31 ,95% CI:0 .19-0 .49 ,P<0 .01) .Conclusion Compared to use mannitol only ,combination with mannitol and glycerin fructose could effectively improve the prognosis of patients with cerebral hemorrhage ,and reduce the side effects .