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 evaluate the effectiveness， safety and economy of baloxavir marboxil in the treatment of influenza， and to provide evidence-based reference for the introduction of new drugs in hospitals and clinical medication decisions. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Epistemonikos， CBM， CNKI， VIP， Wanfang database， official websites and relevant databases of health technology assessment （HTA） institutions， the results of the included studies were descriptively analyzed after literature screening， data extraction and quality evaluation. RESULTS A total of 11 studies were included， involving 6 systematic reviews/meta-analyses and 5 pharmacoeconomic studies. Compared with placebo， baloxavir marboxil significantly shortened the time to alleviation of symptoms （TTAS） and time to resolution of fever （TTRF）， reduced the virus titer change from baseline at 24 h and 48 h after treatment and the incidence of bronchitis， with statistical significance （P＜ 0.05）. Compared with neuraminidase inhibitors （NAIs）， there were no significant differences in shortening TTRF and reducing the incidence of complications， pneumonia and bronchitis （P＞0.05）. The majority of studies suggested that there were no significant differences in shortening TTAS （P＞0.05）. Only very low-quality literature suggested that baloxavir marboxil could significantly reduce the virus titer change from baseline at 24 h and 48 h after treatment. In terms of safety， the incidences of adverse events （AEs） and drug-related adverse events （DRAEs） induced by baloxavir marboxil showed no significant differences， compared with peramivir and zanamivir （P＞0.05）. Some studies considered that the incidences of AEs and DRAEs with baloxavir marboxil were lower than placebo， oseltamivir and laninamivir. Compared with oseltamivir in China and laninamivir in Japan， baloxavir marboxil showed cost-effectiveness advantages. CONCLUSIONS Compared with placebo， baloxavir marboxil has good efficacy， safety and economy. Compared with NAIs （oseltamivir）， baloxavir marboxil has good economic advantages in China， but further high-quality studies are still needed regarding its safety and efficacy.

Brain arteriovenous malformation (bAVM) is a common cerebrovascular disease in clinical practice. Compared with adults, children with bAVM are more prone to rupture and bleeding, and have a higher mortality and disability. Therefore, it is very important to accurately evaluate the bleeding risk of children with bAVM and reasonably select intervention measures to improve the prognosis. The treatment methods of children with bAVM mainly include conservative treatment, microsurgical treatment, endovascular embolization, stereotactic radiosurgery, and multimodal combined treatment. At present, the treatment indications and specific treatment options for children with bAVM are controversial.

Objective:To discuss the clinical curative effect of the minimally invasive percutaneous suture technique of eight times for repairing closed injury extensor tendon zone I of finger.Methods:From February 2017 to January 2020, 12 patients (male 8, female 4) with mallet finger deformity were retrospectively studied, with an average age of 35 years (range, 18-50 years). And all the affected fingers were acute closed rupture of extensor tendon in zone I of single finger, 5 cases of the left finger and 7 cases of the right finger. There were 1 case of the thumb finger, 2 cases of the index finger, 3 cases of the middle finger, 4 cases of the ring finger and 2 cases of the little finger. 12 patients with fresh sputum mallet fingers were with 3-0 thread monofilament suture on extensor tendon zone I of finger in the minimally invasive percutaneous suture technique of eight times, and the distal end of the tendon was fixed to the base of the distal phalanx through the bone hole. Removal of the Kirschner wire 6-8 weeks, the brace was used to fix the affected finger in the dorsal extension. The flexion and extension of the affected finger was gradually strengthened. The function of the affected finger was evaluated according to the Crawford standard after operation and follow-up. The active flexion and extension range of motion of each joint of the affected finger and the contralateral healthy finger were measured, and the total action movement (TAM) of the finger were recorded. Finger function was evaluated according to TAM of the American Association of Hand Surgeons.Results:All operations were successfully completed, the operation time of the patients ranged from 18 to 25 min, with an average of 20.1±0.2 min. There was only a small amount of bleeding in the surgery. All 12 cases were followed up and the follow-up periods ranged from 6 to 14 months, with an average of 10.2±1.1 months. Mallet finger deformities were all corrected postoperatively; there were no knot exposure, skin necrosis and other complications. According to the Crawford standard, 9 cases were excellent, 2 cases were good, and 1 case was fair. The excellent and good rate was 91.7% (11/12). The mean active flexion of distal interphalangeal joints on the wounded finger and healthy finger were 82.11°±2.02° and 84.09°±2.01°, the mean active extension of distal interphalangeal joints on the wounded finger and healthy finger were -2.04°±3.01° and 0.02°±1.02°, there were significant differences between them ( t=2.447, 3.246; P=0.019, 0.004). The degrees of active joint activity of wounded finger were: 91.02°±4.01° of the metacar-pophalangeal joint, 94.04°±2.11° of the proximal interphalangeal joint, 83.01°±2.02° of the distal interphalangeal joint, and 265.05°±13.04° of total active activity; the degrees of active joint activity of healthy finger were: 93.01°±3.21° of the metacar-pophalangeal joint, 94.03°±3.07° of the proximal interphalangeal joint, 85.02°±2.01° of the distal interphalangeal joint, and 269.02°±12.10° of total active activity. The TAMs of the healthy side were 269.02°±12.10°, and the TAMs of the affected side were 265.05°±13.04°, there was no significant difference between them ( P>0.05). According to TAM system assessment criteria: excellent in 9 patients, good in 3 patients, and the excellent and good rate was 100% (12/12). Conclusion:The minimally invasive percutaneous suture technique of eight times can well repair closed injury extensor tendon zone I of finger, can have satisfactory treatment outcome in mallet finger with a simple procedure and good outcome. It is a simple, safe, effective method with minimal invasion.

Objective To study the effect of pirfenidone (PFD) on the transformation of rat corneal stromal cells into fibroblasts in vitro and further explore the anti-fibrotic effect of PFD. Methods The corneal stromal cells from SD rat was isolated and cultured ,and was determined by vimentin stain. The experiment was divided into control group(DMEM+10%FBS),TGF-β1 group(2 ng/mL TGF-β1+DMEM+10%FBS)and PFD group(1 mg/mL PFD+ 2 ng/mL TGF-β1+DMEM+ 10%FBS). Cell proliferation was detected by CCK-8 assay. Collagen Ⅰ,Collagen Ⅲ,Keratocan and CD99 expression were detected by Western blot. Results Compared with control group and TGF-β1 group,the cell proliferation were significantly decreased in PFD group(P<0.05). Western blot showed that PFD can up-regulated Collagen Ⅰand Keratocan but down-regulated Collagen ⅢCD90 expression(P < 0.05). The ratio of Collagen Ⅲ/Collagen Ⅰ in PFD group was lowest in all groups(P < 0.05). Conclusion PFD can resistant fibration in corneal stromal cells may through the inhibition of TGF-β ,which affect the collagen synthesis and Keratocan,CD90 expression.