Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Objective To investigate the relationship between exposure to famine in early life stage and hypertension phenotype and grade in middle and old age. Methods People born between 1951 and 1965 in the 2015 China Health and Elderly Care Follow-up Survey were included in the study, and were divided into unexposed group, fetal exposed group, childhood exposed group and adolescent exposed group according to the time of famine occurrence and birth year of the participants. Logistic regression model was used to explore the effects of different famine exposure periods in early life stage on hypertension classification （including normal high value, grade I, grade II and grade III） and phenotype （including isolated systolic hypertension[ISH], isolated diastolic hypertension [IDH] and combined systolic and diastolic hypertension [SDH]）. Results Compared with unexposed group, fetal famine exposure （OR=1.59, 95% CI :1.10-2.30）, childhood famine exposure （OR=1.67, 95% CI :1.04-2.70） and adolescent famine exposure （OR=3.42, 95% CI : 2.51-4.66） were the risk factors for ISH. Only famine exposure during adolescence （OR=1.54, 95% CI: 1.07-2.21） was a risk factor for SDH. In addition, fetal famine exposure （OR=1.41, 95% CI: 1.05-1.89） and adolescent famine exposure （OR=2.22 , 95% CI: 1.71-2.88） were risk factors for developing grade I hypertension. Famine exposure in childhood （OR=2.45, 95% CI: 1.21-4.94） and famine exposure in adolescence （OR=2.45, 95% CI: 1.44-4.19） were risk factors for grade 2 hypertension. Conclusion Famine exposure in early life stage was associated with the phenotype and grade of hypertension. Therefore, balanced nutrition in early life is important to prevent hypertension in adulthood.

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Objective To evaluate the clinical results of arthroscopic repair of massive rotator cuff tear. Methods The study involved 16 patients with massive rotator cuff tears treated arthroscopically from September 2007 to June 2009. There were 6 males and 11 females at average age 61.5 years (45-75 years). The rotator cuff tears was repaired with arthroscopic double-row reconstruction. The range of motion, pain, strength of flexed elevation and function evaluation score were all recorded before operation and at final follow-up. The results were evaluated by t test and compared according to age and course of disease. Results All patients were healed without complications and the outcome was improved significantly ( P < 0.01 ). The mean VAS score was improved from preoperative 5.6 to postoperative 1.7,the average forward flexion from 69. 1°to 151.2°, the average external rotation from 14.7° to 32.2°, and internal rotation from L1 level to T10, the mean Constant-Murle from 39 to 85, the mean UCLA from 10.4 to 28, the mean SST from 2.8 to 8.8 and the strength of flexed elevation from 10.7% of normal side to 65.0%. Compared with preoperation, there was statistical difference in aspects of pain, range of motion, muscle strength and function in postoperation (P < 0.01 ). Conclusion Arthroscopic doublerow fixation can attain satisfactory results in repair of massive rotator cuff tear.