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Abstract Although treatments for myocardial infarction have advanced significantly, the global mortality due to ischemia and subsequent reperfusion injury remains high. Here, a platelet (PLT) membrane nanocarrier (PL720) that encapsulates L‐arginine and FTY720 to facilitate the cascade‐targeted delivery of these substances to the myocardial injury site and enable the controlled release of L‐arginine and FTY720 is developed. Such an innovative approach shows enhanced cardioprotection through multiple target strategies involved in ischemia–reperfusion injury and late reperfusion inflammation. During the ischemia–reperfusion phase, PL720 targets and accumulates in damaged coronary arteries. PL720 rapidly releases L‐arginine, stimulating endothelial cells to produce NO, thereby dilating blood vessels and promoting blood flow recovery, while FTY720's sustained release exerts anti‐apoptotic effects. During the late reperfusion inflammatory phase, PL720 is captured by circulating inflammatory monocytes and transported into a deeper ischemic myocardial lesion. PL720 promotes macrophage polarization and accelerates the inflammatory repair. Furthermore, the issue of bradycardia associated with the clinical use of FTY720 is innovatively relieved. Therefore, PL720 is a vascular injury and inflammation dual targeting strategy, exhibiting significant potential for multi‐targeted therapy and clinical translation for cardiac injury.

Objective To develop and validate the efficacy of a 3D‐printed screw‐rod auxiliary system for unstable atlas fractures. Methods This research is a retrospective analysis, and a total of 14 patients, including 11 males and three females, were enrolled in our hospital from January 2017 to March 2019 who underwent occipitocervical fusion assisted by the 3D‐printed screw‐rod auxiliary system were reviewed, and with an average age of 53.21 ± 14.81 years, an average body mass index (BMI) of 23.61 ± 1.93 kg/m2. The operation time, blood loss and radiation times during the operation were recorded. The maximum fracture displacement values of pre‐ and post‐operation were measured based on CT imaging. All screw grades were evaluated after surgery. The occipital‐cervical 2 (O‐C2) angle and occipitocervical inclination (OCI) angle of pre‐operation, post‐operation and the last following‐up were measured. The dysphagia scale 3 months after surgery and at the last follow‐up, the Neck Disability Index (NDI) 3 months after surgery and at the last follow‐up were assessed. Results All patients were completed the surgery successfully. There was no patient with severe dysphagia or aggravation of nerve injury. The follow‐up was from 12 to 14 months, and with an average of 12.5 months. The average surgery time, average blood loss and average radiation times for the 14 patients were 112.14 min, 171.43 mL and 5.07 times, respectively. There was a significant difference in maximum fracture displacement between pre‐ and post‐operation values (P

Abstract Background To determine the effectiveness and sustainability of supervised balance training in people with chronic ankle instability (CAI) with grade III ligament injury. Methods Twenty young adults (12 males and 8 females) diagnosed with CAI with grade III ligament injury underwent 3 months of supervised balance training. The self‐reported functional questionnaire, plantar pressure (walking and single leg standing), and isokinetic ankle strength were consecutively evaluated at pre‐training, 3 months, 6 months and one year. Paired T tests were used to explore changes in muscle strength and plantar pressures following the supervised balance training. According to whether the patient had sprain recurrence, the patients were divided into sprain recurrence group and control group. The risk factors of sprain recurrence were explored with univariate analysis and multivariable logistic regression. Results The self‐reported functional scores, the plantar pressure distribution and the muscle strength showed significant immediate improvements after 3 months of supervised balance training. At 6 months post‐training, peak force under 2nd metatarsal, time to peak force under the medial hindfoot, time to boundary measurements and dorsiflexion, and eversion strength were partly declined to the pre‐training level. 16 patients (80%) resumed the daily life and sports without sprain recurrence during the follow‐up. Four patients (20%) reported ankle sprain during the follow‐up, and the sprain recurrence group showed significantly higher Beighton scores (p = 0.012) and weaker initial inversion strength (p = 0.022) than the control group. Conclusions Three months' of supervised balance training could effectively improve postural control and muscle strength of CAI cases with grade III ligament injury, although these improvements would partially deceased over time. Additional strength exercises for dorsiflexion and eversion should be supplemented from 6 months. Higher Beighton score and initial inversion muscle strength weakness might increase the risk of sprain recurrence. Trial registration ChiCTR, ChiCTR1900023999, Registered 21 June 2019, https://www.chictr.org.cn/edit.aspx?pid=39984&htm=4

BackgroundIntermittent hypoxia (IH) induced by obstructive sleep apnea is the key factor involved in cardiovascular fibrosis. Under persistent hypoxia condition, endothelial cells respond by endothelial‐to‐mesenchymal transition (EndMT), which is associated with cardiovascular fibrosis. Prolyl 4‐hydroxylase domain protein 3 (PHD3) is a cellular oxygen sensor and its expression increased in hypoxia. However, its role in obstructive sleep apnea–induced EndMT and cardiovascular fibrosis is still uncertain. We investigated the potential mechanism of obstructive sleep apnea–induced cardiac perivascular fibrosis and the role of PHD3 in it. Methods and ResultsIn vivo, C56BL/6 mice were exposed to IH for 12 weeks. PHD3 expression was changed by lentivirus‐mediated short‐hairpin PHD3 and lentivirus carrying PHD3 cDNA. EndMT related protein levels, histological and functional parameters were detected after 12 weeks. In vitro, human umbilical vein endothelial cells were treated with IH/short‐hairpin PHD3/lentivirus carrying PHD3 cDNA to explore the mechanism of PHD3 in altered function of human umbilical vein endothelial cells. We found that chronic intermittent hypoxia increase PHD3 expression and EndMT. In vivo, IH accelerate cardiac dysfunction and aggravate collagen deposition via the process of EndMT. And, when PHD3 were overexpressed, cardiac dysfunction and collagen excessive deposition were improved. In vitro, IH induced EndMT, which endow human umbilical vein endothelial cells spindle morphology and an enhanced ability to migration and collagen secretion. PHD3 overexpression in cultured human umbilical vein endothelial cells ameliorated IH–induced EndMT through inactivating hypoxia‐inducible factor 1 alpha and small mothers against decapentaplegic 2 and 3. ConclusionsObstructive sleep apnea–induced cardiac perivascular fibrosis is associated with EndMT, and PHD3 overexpression might be beneficial in the prevention of it by inhibiting EndMT. PHD3 overexpression might have therapeutic potential in the treatment of the disease.