Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide from Wuhan. An easy-to-use index capable of the early identification of inpatients who are at risk of becoming critically ill is urgently needed in clinical practice. Hence, the aim of this study was to explore an easy-to-use nomogram and a model to triage patients into risk categories to determine the likelihood of developing a critical illness. METHODS: A retrospective cohort study was conducted. We extracted data from 84 patients with laboratory-confirmed COVID-19 from one designated hospital. The primary endpoint was the development of severe/critical illness within 7 days after admission. Predictive factors of this endpoint were selected by LASSO Cox regression model. A nomogram was developed based on selected variables. The predictive performance of the derived nomogram was evaluated by calibration curves and decision curves. Additionally, the predictive performances of individual and combined variables under study were evaluated by receiver operating characteristic curves. The developed model was also tested in a separate validation set with 71 laboratory-confirmed COVID-19 patients. RESULTS: None of the 84 inpatients were lost to follow-up in this retrospective study. The primary endpoint occurred in 23 inpatients (27.4%). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were selected as the final prognostic factors. A nomogram was developed based on the NLR and CRP. The calibration curve and decision curve indicated that the constructed nomogram model was clinically useful. The AUCs for the NLR, CRP and Combined Index in both training set and validation sets were 0.685 (95% CI: 0.574-0.783), 0.764 (95% CI: 0.659-0.850), 0.804 (95% CI: 0.702-0.883), and 0.881 (95% CI: 0.782-0.946), respectively. CONCLUSIONS: Our results demonstrated that the nomogram and Combined Index calculated from the NLR and CRP are potential and reliable predictors of COVID-19 prognosis and can triage patients at the time of admission.

A meta-analysis: The association between interleukin-17 pathway gene polymorphism and gastrointestinal diseases.

BACKGROUND: A number of studies have been conducted to investigate associations between genetic polymorphisms in interleukin-17 (IL-17) pathway and the risk of gastrointestinal diseases. Results, however, have been inconclusive. We aimed to evaluate these associations through a meta-analysis. METHODS: We searched electronic databases (PubMed, Embase, Web of Science, CBM and CNKI) to identify papers, published before October 2014, on associations between polymorphisms in the IL-17 pathway genes (rs2275913, rs763780, rs3748067, rs3819025, rs9382084, rs12203582 and rs8193036) and the risk of gastrointestinal diseases. We estimated the strength of candidate associations through calculating pooled odds ratios (ORs) and 95% confidence intervals (CIs). A test of heterogeneity, a false-positive report probability (FPRP) test, sensitivity analyses and examination for bias were further conducted to evaluate cumulative evidence of these associations. RESULTS: We identified 25 eligible case-control studies retrieved from 16 articles involved in a total of 4507 cases and 5733 controls. Of them, IL-17 (-197G/A) polymorphism (rs2275913) was statistically significantly associated with risk of gastrointestinal diseases, especially for gastrointestinal malignancy and gastroduodenal diseases. Based on heterogeneity (P<0.05) and FPRP (P<0.2) identified in this study, we graded cumulative epidemiological evidence of an association with gastrointestinal diseases for this polymorphism. However, IL-17 (7488T/C) polymorphism (rs763780) did not show significant associations with gastrointestinal diseases either individually or overall (P>0.05). CONCLUSION: Our study provides moderate evidence that IL-17 (-197G/A) polymorphism may be a potential risk factor for gastrointestinal diseases, particularly for malignancy. Further validation of this association in a large homogeneous study is warranted.

[Short-segment posterior pedicle screw combined with vertebral arch bone grafting for thoracolumbar burst fractures].

OBJECTIVE: To analyze the clinical effects of short-segment posterior pedicle screw combined with transpedicle vertebral bone grafting in treating thoracolumbar burst fractures. METHODS: From March 2008 to March 2013, 62 patients with thoracolumbar burst fractures were treated with short-segment posterior pedicle screw combined with transpedicle vertebral bone grafting. Including 40 males and 22 females, the age from 17 to 65 years old with an average of 38 years. According to AO classification, 34 cases were type A3.1, 7 cases were type A3.2 and 21 cases were type A3.3. Load-sharing scores were from 4 to 6 points with an average of 5.4 points. According to ASIA grade, 2 cases were grade C, 5 cases were grade D and 55 cases were grade E. Preoperative, postoperative at 3 d and final follow-up, the Cobb angle, the relative height of anterior vertebral body and the encroachment rate of spinal canal were measured by X-ray films and computed tomography (CT) scan, meanwhile, the information of bone healing and spinal nerves recovery were observed. RESULTS: All patients were followed up from 11 to 14 months with an average of 12.2 months. The duration of removing internal fixation were from 9 to 13 months (averaged, 11.5 months). One suffered from infection and was cured by debridement. Two cases had mild pain of back. At 6 months after operation, according to ASIA grade to evaluate never function, 1 case was grade C, 3 cases were grade D and 58 cases were grade E. X-ray and CT showed the fractures obtained good union at final follow-up. The Cobb angle, the relative height of anterior vertebral body and the encroachment rate of spinal canal had obviously improved at 3 days after operation (P<0.05); but there was no significant differences between postoperative at 3 d and final follow-up (P>0.05). CONCLUSION: Short-segment posterior pedicle screw combined with transpedicle vertebral bone grafting is an effective method to treat thoracolumbar burst fractures. It can reduce the loss of postoperative correction and prevent the internal fixation failure.