The repair of critical bone defects is a hotspot of orthopedic research. With the development of bone tissue engineering (BTE), there is increasing evidence showing that the combined application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes, with hydrogels, scaffolds, and other bioactive materials has made great progress, exhibiting a good potential for bone regeneration. Recent studies have found that miRNAs, proteins, and other cargo loaded in EVs are key factors in promoting osteogenesis and angiogenesis. In BTE, the expression profile of the intrinsic cargo of EVs can be changed by modifying the gene expression of MSCs to obtain EVs with enhanced osteogenic activity and ultimately enhance the osteoinductive ability of bone graft materials. However, the current research on MSC-EVs for repairing bone defects is still in its infancy, and the underlying mechanism remains unclear. Therefore, in this review, the effect of bioactive materials such as hydrogels and scaffolds combined with MSC-EVs in repairing bone defects is summarized, and the mechanism of MSC-EVs promoting bone defect repair by delivering active molecules such as internal miRNAs is further elucidated, which provides a theoretical basis and reference for the clinical application of MSC-EVs in repairing bone defects.

Clinical treatment strategies for musculoskeletal disorders have been a hot research topic. Accumulating evidence suggests that hydrogels loaded with MSC‐derived EVs show great potential in improving musculoskeletal injuries. The ideal hydrogels should be capable of promoting the development of new tissues and simulating the characteristics of target tissues, with the properties matching the cell‐matrix constituents of autologous tissues. Although there have been numerous reports of hydrogels loaded with MSC‐derived EVs for the repair of musculoskeletal injuries, such as intervertebral disc injury, tendinopathy, bone fractures, and cartilage injuries, there are still many hurdles to overcome before the clinical application of modified hydrogels. In this review, we focus on the advantages of the isolation technique of EVs in combination with different types of hydrogels. In this context, the efficacy of hydrogels loaded with MSC‐derived EVs in different musculoskeletal injuries is discussed in detail to provide a reference for the future application of hydrogels loaded with MSC‐derived EVs in the clinical treatment of musculoskeletal injuries.

Background: Polygenic risk scores (PRS) and lifestyle factors are associated with colorectal cancer (CRC), but whether their associations and joint effects vary according to age at CRC onset remains unclear. We evaluated age‐related heterogeneity in the associations of genetic risk and lifestyle with CRC and examined their additive interaction in early‐ and late‐onset CRC. Methods: We analyzed data from 405,453 cancer‐free participants aged 38–73 years at baseline in the UK Biobank. PRS and a healthy lifestyle score (based on eight modifiable factors) were assessed. Age‐scale Cox proportional hazards models estimated hazard ratios (HRs) for CRC risk by age at onset. Heterogeneity across age intervals was assessed using likelihood ratio tests. Additive interaction was assessed using the relative excess risk due to interaction (RERI), and differences in standardized incidence rates were evaluated. Results: During a median follow‐up of 13.65 years, 6620 CRC cases were identified. Compared with low genetic risk, high genetic risk was associated with HRs of 3.72, 3.32, 2.80, and 2.01 for CRC occurring at ages < 55, 55–64, 65–74, and ≥ 75 years, respectively, with significant heterogeneity across age intervals ( p for heterogeneity < 0.001). Compared with a favorable lifestyle, the corresponding HRs for an unfavorable lifestyle were 1.10, 1.50, 1.58, and 1.28, respectively, with evidence of overall heterogeneity ( p for heterogeneity = 0.015). For late‐onset CRC, positive additive interactions were observed for an unfavorable lifestyle combined with intermediate or high genetic risk, whereas no such interaction was detected for early‐onset CRC. Conclusions: The associations of genetic susceptibility and baseline lifestyle with CRC varied according to age at onset. Positive additive interaction between genetic risk and an unfavorable lifestyle was observed for late‐onset but not early‐onset CRC. These findings provide further evidence that the relative and joint associations of genetic and lifestyle factors with CRC vary across the life course.

BACKGROUND Wrist-worn wearables have become an increasingly popular way to assess exercise intensity and energy expenditure (EE) in health care and various other settings. However, there is still few research on the validity and reliability of wrist-worn wearables in monitoring exercise parameters at different intensities by people with different levels of physical activity. OBJECTIVE This study assessed the validity and reliability of the Mio Smart Bracelet (Lexin Mio Band 1) in measuring the heart rate (HR) and EE with different physical activity levels during exercise at different intensities. The second objective was to determine if wear position (i.e. dominate or nondominate hand) would cause differences in assessments. METHODS A total of 65 participants (N = 65; 63% female, n = 41; 37% male, n = 24) wore the Lexin smart bracelet (Mio Band 1) and its validity and reliability were assessed against two “gold standard” devices: the Polar H10 heart rate band (for HR) and the gas-analysis system (GAS, Metalyzer 3B) for EE. The participants completed one maximal oxygen uptake (VO2max) test and a running exercise test twice (10-min resting period; 6-min treadmill exercise under three intensities; 10-min recovery period). To measure test-retest reliability, intra-group correlation coefficient (ICC) were determined between the first and second treadmill test. Validity was determined by comparing the Mio with the gold standard (Polar and GAS), using mean differences, mean absolute percentage errors (MAPE), ICC and Bland-Altman analysis. RESULTS For the reliability, the HR consistency between the tests was significant (p < 0.05) in all the states except the Mio in HPAL (P < 0.05), while the EE consistency between the tests, only the right-wrist Mio showed significance in the low-physical-activity level (LPAL) population, and for the moderate-intensity exercise (MIE) and the high-intensity exercise (HIE) in the moderate-physical-activity level (MPAL) population. With regard to the validity, the MAPE between the Polar and the left- and right-wrist Mio bracelets (henceforth “left and right Mios”) ranged from 1% to 7.55%, while the MAPE between the left and right Mios ranged from 10.37% to 32.42%. The HR consistency in the LPAL, MPAL, and high-physical-activity level (HPAL) populations was significant between polar and the left and right Mios at different exercise intensities (P < 0.01), and insignificant only in HPAL group under HIE (P>0.05). As for the EE consistency, it was significant in the left and right Mios under MIE and in the right Mio under HIE in the LPAL group; in the left and right Mios under MIE or HIE, and in the right Mio during recovery in MPAL group; and in the left and right Mios under MIE in the HPAL group (P < 0.05). CONCLUSIONS For HR measurement, the Lexin Mio bracelet showed good reliability and validity among people with different physical activity levels who were exercising under various intensities in a laboratory setting. However, for the estimation of the EE, the Lexin Mio bracelet showed low reliability and validity. CLINICALTRIAL This study was approved by the Experimental Ethics Committee for Sports Science of Beijing Sport University (registration number 2020133H). The participants were informed of the study purpose and procedures and then signed a written informed consent form before enrollment in this study.