Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

Osteoarthritis (OA) is a common chronic joint disease,whose main pathological changes are the degeneration of articular cartilage and secondary bone hyperplasia.The limitation of current treatment methods including pain relief and joint replacement surgery is that they cannot fundamentally improve the damage of articular cartilage.The emergence of disease-modifying osteoarthritis drugs (DMOAD) may break the above limitations.They fundamentally inhibit the structural degeneration of articular cartilage by participating in the regulation of cartilage metabolic balance, regulation of subchondral bone remodeling,and control of local inflammation.Thereby,OA patients will get symptom improvement including pain relief and joint function restoration,delay the artificial joint replacement surgery, and improve the quality of life. There are still no DMOAD drugs widely available on the market worldwide.This paper reviews the background of R&D,the classification of mechanisms of action and research progress of representative drugs under different inechanisms so as to provide reference for future research.

Objective::This study aimed to evaluate the incidence and associated clinical risk factors for preeclampsia (PE) and its subtypes in a large multicentre retrospective study of Beijing, China.Methods::This study was conducted as a secondary analysis from the Gestational diabetes mellitus Prevalence Survey (GPS), a multicentre retrospective cohort study, which included 15 hospitals in Beijing, China. This analysis included 15,003 pregnant women who delivered in Beijing from June 20 th to November 30 th, 2013. The incidence of PE was calculated. Risk factors for PE, including maternal age, pre-gestational body mass index (BMI), parity, chronic hypertension, pre-existing diabetes, and gestational diabetes mellitus, were assessed. PE was defined as early- or late-onset PE based on clinical manifestations during the week of delivery, and mild or severe PE based on the severity of the disease. Logistic regression analysis was used to quantify the association with the risk factors, and data were displayed as odds risks ( OR) and 95% confidence interval ( CI). Results::The overall incidence of PE was 2.65% (397/15,003). The prevalence of early-onset and late-onset PE was 0.36% (54/15,003) and 2.29% (343/15,003), respectively. The prevalence of mild and severe PE was 0.91% (137/15,003) and 1.73% (260/15,003), respectively. Risk factors including high BMI considered overweight (adjusted odds risk (a OR): 1.48; 95% CI: 1.06-2.05; P= 0.02) and obesity (a OR: 2.15; 95% CI: 1.50-3.08; P < 0.001), nulliparity (a OR: 1.73; 95% CI: 1.32-2.25; P < 0.001), multiple gestation (a OR: 4.58; 95% CI: 2.86-7.32; P < 0.001), and chronic hypertension (a OR: 34.95; 95% CI: 26.60-45.93; P < 0.001), were associated with increased risk for PE. Only chronic hypertension (a OR: 13.75; 95% CI: 4.78-39.58; P < 0.001) was a significant risk factors for early-onset PE, whereas high BMI considered both overweight (a OR: 1.54; 95% CI: 1.09-2.18; P= 0.01) and obesity (a OR: 2.23; 95% CI: 1.53-3.27; P < 0.001), nulliparity (a OR: 2.00; 95% CI: 1.49-2.68; P < 0.001), multiple gestation (a OR: 4.11; 95% CI: 2.40-7.05; P < 0.001), and chronic hypertension (a OR: 35.57; 95% CI: 26.66-47.47; P < 0.001) were more relevant risk factors for late-onset PE. Risk factors including obesity (a OR: 2.20; 95% CI: 1.28-3.76; P < 0.01 and a OR: 1.80; 95% CI: 1.16-2.80; P= 0.01), nulliparity (a OR: 2.28; 95% CI: 1.44-3.60; P < 0.001 and a OR: 1.48; 95% CI: 1.09-2.02; P= 0.01), multiple gestation (a OR: 5.50; 95% CI: 2.87-10.67; P < 0.001 and a OR: 3.51; 95% CI: 1.93-6.41; P < 0.001), and chronic hypertension (a OR: 33.98; 95% CI: 22.20-52.01; P < 0.001 and a OR: 35.03; 95% CI: 25.40-48.31; P < 0.001) were associated with mild and severe PE. Moreover, we found that women with an increasing number of these risk factors had a higher risk of developing PE than pregnant women without any identified risk factors. Conclusion::The incidence of PE in this study is consistent with previous reported studies. Our findings indicate chronic hypertension and multiple gestation are the most important risk factors for PE in Chinese pregnant women. The risk for developing PE is associated with both the type and abundance of risk factors. These factors are valuable when monitoring patients at risk for PE, as this can help ensure an earlier diagnosis and prediction in women who are more likely to develop PE.

Objective::This study aimed to evaluate the incidence and associated clinical risk factors for preeclampsia (PE) and its subtypes in a large multicentre retrospective study of Beijing, China.Methods::This study was conducted as a secondary analysis from the Gestational diabetes mellitus Prevalence Survey (GPS), a multicentre retrospective cohort study, which included 15 hospitals in Beijing, China. This analysis included 15,003 pregnant women who delivered in Beijing from June 20 th to November 30 th, 2013. The incidence of PE was calculated. Risk factors for PE, including maternal age, pre-gestational body mass index (BMI), parity, chronic hypertension, pre-existing diabetes, and gestational diabetes mellitus, were assessed. PE was defined as early- or late-onset PE based on clinical manifestations during the week of delivery, and mild or severe PE based on the severity of the disease. Logistic regression analysis was used to quantify the association with the risk factors, and data were displayed as odds risks ( OR) and 95% confidence interval ( CI). Results::The overall incidence of PE was 2.65% (397/15,003). The prevalence of early-onset and late-onset PE was 0.36% (54/15,003) and 2.29% (343/15,003), respectively. The prevalence of mild and severe PE was 0.91% (137/15,003) and 1.73% (260/15,003), respectively. Risk factors including high BMI considered overweight (adjusted odds risk (a OR): 1.48; 95% CI: 1.06-2.05; P= 0.02) and obesity (a OR: 2.15; 95% CI: 1.50-3.08; P < 0.001), nulliparity (a OR: 1.73; 95% CI: 1.32-2.25; P < 0.001), multiple gestation (a OR: 4.58; 95% CI: 2.86-7.32; P < 0.001), and chronic hypertension (a OR: 34.95; 95% CI: 26.60-45.93; P < 0.001), were associated with increased risk for PE. Only chronic hypertension (a OR: 13.75; 95% CI: 4.78-39.58; P < 0.001) was a significant risk factors for early-onset PE, whereas high BMI considered both overweight (a OR: 1.54; 95% CI: 1.09-2.18; P= 0.01) and obesity (a OR: 2.23; 95% CI: 1.53-3.27; P < 0.001), nulliparity (a OR: 2.00; 95% CI: 1.49-2.68; P < 0.001), multiple gestation (a OR: 4.11; 95% CI: 2.40-7.05; P < 0.001), and chronic hypertension (a OR: 35.57; 95% CI: 26.66-47.47; P < 0.001) were more relevant risk factors for late-onset PE. Risk factors including obesity (a OR: 2.20; 95% CI: 1.28-3.76; P < 0.01 and a OR: 1.80; 95% CI: 1.16-2.80; P= 0.01), nulliparity (a OR: 2.28; 95% CI: 1.44-3.60; P < 0.001 and a OR: 1.48; 95% CI: 1.09-2.02; P= 0.01), multiple gestation (a OR: 5.50; 95% CI: 2.87-10.67; P < 0.001 and a OR: 3.51; 95% CI: 1.93-6.41; P < 0.001), and chronic hypertension (a OR: 33.98; 95% CI: 22.20-52.01; P < 0.001 and a OR: 35.03; 95% CI: 25.40-48.31; P < 0.001) were associated with mild and severe PE. Moreover, we found that women with an increasing number of these risk factors had a higher risk of developing PE than pregnant women without any identified risk factors. Conclusion::The incidence of PE in this study is consistent with previous reported studies. Our findings indicate chronic hypertension and multiple gestation are the most important risk factors for PE in Chinese pregnant women. The risk for developing PE is associated with both the type and abundance of risk factors. These factors are valuable when monitoring patients at risk for PE, as this can help ensure an earlier diagnosis and prediction in women who are more likely to develop PE.