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IntroductionIn response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson's disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.MethodsWe conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.ResultsEleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).ConclusionsResults of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into β-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M$$\varphi $$ φ s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti‐inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time‐scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.

Objectives The purpose of this study was to examine the association of prepubertal body mass index (BMI) and weight status with pubertal development in boys and girls in Chongqing, China. Methods In a longitudinal study, 1237 students (695 boys and 542 girls) were recruited from Chongqing, China, and examined at baseline, then followed every 6 months for three and a half years. Height, weight, testicular volume, and breast development were measured at every examination. Age of first spermatorrhea and menarche were obtained from self‐report. Subjects were divided into normal weight, overweight, and obese groups according to baseline BMI. Multivariable Cox regression analysis was used to examine the association of BMI and weight status with pubertal development. Results In girls, higher prepubertal BMI increased the chance of earlier menarche (hazards ratio (HR): 1.205, 95% confidence interval (95% CI): 1.151‐2.261) and breast development (HR: 1.092, 95% CI: 1.045‐1.142). Girls in the overweight (HR: 2.605, 95% CI: 1.716‐3.956) and obese (HR: 2.565, 95% CI: 1.603‐4.103) groups had an increased risk of early menarche compared with those in the normal weight group, while only overweight was associated with an increased risk for earlier breast development (HR: 1.469, 95% CI: 1.024‐2.108). In boys, higher prepubertal BMI was significantly associated with the timing of first spermatorrhea (HR: 1.054, 95% CI: 1.004‐1.106) and testicular development (HR: 1.098, 95% CI: 1.063‐1.135). Overweight (HR: 1.672, 95% CI: 1.204‐2.322) and obesity (HR: 1.598, 95% CI: 1.135‐2.249) increased the hazard of earlier testicular development compared with the normal weight group, while no significant differences were detected among the three weight groups in terms of time to first spermatorrhea. Conclusions Higher prepubertal BMI was associated with earlier puberty in both Chinese boys and girls.

Granulocyte colony-stimulating factor (G-CSF) is atherapeutic candidate for stroke that has demonstrated anti-inflammatory and neuroprotective properties. Data from preclinical and clinical studies have suggested the safety and efficacy of G-CSF in stroke; however, the exact effects and utility of this cytokine in patients remain disputed. We performed a meta-analysis of randomized controlled trials of G-CSF in ischemic and hemorrhagic stroke to assess its clinical safety and efficacy. Electronic databases were searched for relevant publications in English and Chinese. A total of 14 trials met the inclusion criteria. G-CSF (cumulative dose range, 1–135μg/kg/day) was tested against placebo in a total of 1037 participants. There was no difference in the rate of mortality between groups (odds ratio, 1.23; 95% confidence interval, 0.76–1.97, p = 0.40). Moreover, the rate of serious adverse events did not differ between groups and provided evidence for the safety of G-CSF administration in stroke patients (odds ratio, 1.11; 95% confidence interval, 0.77–1.61, p = 0.57). No significant outcome benefits were noted with respect to the National Institutes of Health Stroke Scale (mean difference, -0.16; 95% confidence interval, -1.02–0.70, p = 0.72); however, improvements were noted with respect to the Barthel Index (mean difference, 8.65; 95% confidence interval 0.98–16.32; p = 0.03). In conclusion, it appears to be safe in administration of G-CSF, but it will increase leukocyte count. G-CSF was weakly significant benefit with improving the BI scores, while there was no improvement in the NIHSS scores. Larger and more robustly designed trials of G-CSF in stroke are needed to confirm the results.

Background: Existing evidence regarding how time spent on various types of sedentary behavior (SB) in relation to physical fitness (PF) and academic performance (AP) in children and adolescents is limited. This cross-sectional study aimed to explore the associations of SB types with PF and AP among 8–19-year-old Chinese students. Methods: A total of 1164 students were recruited from five schools in Zhejiang province, China. Children’s SB was assessed by a valid questionnaire and AP was represented by scores on four courses. PF was measured by Chinese National Student PF Standard battery. The associations were assessed using linear mixed-effects models adjusted for age, school, grade, and class. Results: Students’ screen-based SB was observed to be negatively associated with PF in girls (p < 0.05). Screen-based SB was inversely associated with AP in both girls and boys (p < 0.001). The significant interaction between weekdays and weekends, and SB on AP was observed in girls (p < 0.001). On weekends, screen-based SB ≥ 6 h/day (<3 h/day as reference group) was significantly and negatively associated with AP (p < 0.01 for both sex). Conclusions: Longer screen-based SB, especially on weekends, was related to poorer AP in 8–19-year-old Chinese students. Our findings suggest that restrictions on any type of screen-based SB for leisure on weekends are beneficial to AP in Chinese students.

Objective: To explore the relationships of asymmetric deep medullary veins (ADMV) to asymmetric cortical veins (ACV), leptomeningeal collaterals and prognosis in patients with occlusion of a large cerebral artery.Methods: Clinical and imaging data of 56 patients with occlusion of a large cerebral artery were collected and reviewed. We assessed the time delayed between stroke onset and MR imaging (within 24 h of stroke onset), extension of cerebral infarction using the Alberta stroke program early CT score based on diffusion-weighted imaging (ASPECTs). ADMV and ACV were assessed using susceptibility-weighted imaging. The presence of ADMV (ACV) was defined as deep medullary veins (cortical veins) of the affected hemisphere that were greater in number and diameter than in the contralateral hemisphere. To evaluate leptomeningeal collaterals, the hyperintense vessel sign (HVS) was detected using T2 weighted fluid attenuated inversion recovery images. At 90 days, a modified Rankin scale score (mRS) was assessed to evaluate the clinical outcome.Results: Of 56 patients, 27 presented with ADMV. Those patients who presented with and without ADMV differed significantly in HVS and ACV (P < 0.05) but not in time delayed between stroke onset and MR imaging, age, gender, stroke risk factors, baseline NIHSS score, or modified Rankin scale score at 3 months (P > 0.05). Logistic regression analysis found that the presence of ADMV was independently related to HVS and ACV (ACV: OR 95% C.I., 1.287–4.368; HVS: OR 95% C.I., 1.132–4.887).Conclusions: The presence of ADMV on SWI was associated with prominent ACV and good leptomeningeal collateral flow but was not related to prognosis in patients with occlusion of a large cerebral artery.