With the increasing popularity of minimally invasive surgery, to develop an injectable bone would be highly preferable for the repair of bone nonunions and defects. However, the use of dissociated cells and exogenous carriers to construct injectable bone faces several drawbacks. To circumvent these limitations, we first harvested a cell sheet from rabbit bone marrow stromal cells using a continuous culture method and a scraping technique. The obtained sheet was then cut into fragments of multicellular aggregates, each of which was composed of a certain number of cells, extracellular matrix, and intercellular connections. The aggregates showed apparent mineralization properties, high alkaline phosphatase activity, increased osteocalcin content, and upregulated bone markers, implying their in vitro osteogenic potential. Then, serum-free medium (the control group), dissociated cell suspension (the cell group), and suspension of multicellular aggregates (the aggregate group) were injected subcutaneously on the back of the nude mice to evaluate ectopic bone formation. The results revealed that the aggregate group showed significantly larger and denser bone at the injection sites than the cell group, whereas bone formation did not occur in the control group. Additionally, when injecting them locally into the mandibular fracture gap of delayed healing in a rabbit model, we observed the most improved bone healing in the aggregate group. More cells survive and retain at the injection sites in the aggregate group than that in the cell group postoperatively. Our study indicates that the multicellular aggregates might be considered a promising strategy to generate injectable bone tissue and improve the efficacy of cell therapy.

Background: Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA. Methods: The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation. (Continued on next page)Results: Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: − 0.31; 95% confidence interval (CI): − 0.55 to − 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: − 0.54 to − 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: − 0.67 to − 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: − 0.67 to − 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05). Conclusions: Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

Background: Retear after arthroscopic rotator cuff repair (ARCR) consistently challenges medical staff and patients, and the incidence of retear after surgery is 10%-94%. The purpose of this study was to identify the risk factors that cause retear after ARCR and provide theoretical guidance for clinical intervention to reduce the occurrence of postoperative rotator cuff retear. Methods: The protocol for this meta-analysis was registered with PROSPERO (CRD42021225088). PubMed, Web of Science, and Embase were searched for observational studies on risk factors for rotator cuff retear after arthroscopic repair. Meta-analytical methods were used to determine the odds ratio or weighted mean difference of potential risk factors related to postoperative rotator cuff retear. Stata 15.1 was used to quantitatively evaluate the publication bias of the statistical results. Results: Fourteen studies from 6 countries with a total of 5693 patients were included. The meta-analysis revealed that the risk factors for retear after rotator cuff repair were age, body mass index, diabetes, subscapularis and infraspinatus fatty infiltration, symptom duration, bone mineral density, tear length, tear width, tear size area, amount of retraction, critical shoulder angle, acromiohumeral interval, distance from the musculotendinous junction to the glenoid, operative duration, biceps procedure, and postoperative University of California Los Angeles shoulder score. Conclusion: These findings can help clinical medical staff identify patients who are prone to retear early after arthroscopic repair and develop targeted prevention and treatment strategies for modifiable risk factors, which are of great significance for reducing the occurrence of rotator cuff retear after ARCR.

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton. In this study, we systematically reviewed Chinese AS epidemiological studies from the past 15 years to elucidate its prevalence and provide scientific data for China's health care system. AS epidemiological research in China was summarized by conducting a literature review. A review and statistical analysis of the literature on the epidemiology of AS in mainland China published from May 2005 to May 2019 were performed via a meta-analysis. We calculated the prevalence of AS and analysed differences by sex, region, and population source using STATA12.0 software. Eleven papers including 122,558 subjects from mainland China were included. Over the past 15 years, the total prevalence of AS in mainland China was 0.29% (95% CI 0.22-0.35%), ranging from 0.42% (95% CI 0.31-0.52%) in males to 0.15% (95% CI 0.13-0.18%) in females; the difference in the prevalence of AS by sex was statistically significant (P < 0.001). The prevalence of AS in both southern and northern China was 0.31% (95% CI 0.21-0.42% and 0.21-0.40%, respectively), with no significant difference noted (P = 0.816 > 0.005). The prevalence of AS in Chinese military populations was 0.27% (95% CI 0.09-0.45%), and in community populations, it was 0.29% (95% CI 0.23-0.35%). There was no statistically significant difference in the prevalence of AS by sampling resource (P = 0.115 > 0.005). The prevalence of AS in China was 0.29% and continues to increase. Sex differences in its prevalence were identified; the prevalence rate was 2.8 times higher in males than in females. Epidemiologists in China should formulate precise scientific investigations to provide additional authoritative epidemiological data for the prevention and treatment of AS.

Background and purpose: Activation of muscarinic M3 mucarinic acetylcholine receptors (M3-mAChRs) has been previously shown to confer short-term cardioprotection against ischaemic injuries. However, it is not known whether activation of these receptors can provide delayed cardioprotection. Consequently, the present study was undertaken to investigate whether stimulation of M3-mAChRs can induce delayed preconditioning in rats, and to characterize the potential mechanism. Experimental approach: Rats were pretreated (24 h), respectively, with M3-mAChRs agonist choline, M3-mAChRs antagonist 4-DAMP or M2-mAChRs antagonist methoctramine followed by the administration of choline. This was followed by 30 min of ischaemia and then 3 h of reperfusion. Ischaemia-induced arrhythmias and ischaemia-reperfusion (I/R)-induced infarction were determined. The phosphorylation status of connexin43 (Cx43) after 30 min ischaemia, and the expression level of Hsp70, cyclooxygenase-2 (COX-2) and iNOS effected by administration of choline were also measured. Key results: Compared to the control group, pretreatment with choline significantly decreased ischaemia-induced arrhythmias, reduced the total number of ventricular premature beats, the duration of ventricular tachycardia episodes and markedly reduced I/R-induced infarct size. Furthermore, choline attenuated ischaemia-induced dephosphorylation of Cx43, and up-regulated the expression of Hsp70 and COX-2. Administration of 4-DAMP abolished these changes, while methoctramine had no effect. Conclusions and implications:Our results suggest that stimulation of M3-mAChRs with choline elicits delayed preconditioning, which we propose is the result of up-regulation of the expression of COX-2 and inhibition of the ischaemia-induced dephosphorylation of Cx43. Therefore, M3-mAChRs represent a promising target for rendering cardiomyocytes tolerant to ischaemic injury.

The present study was designed to study the effects of As₂O₃ on QT interval prolongation and to explore the potential ionic mechanisms in isolated rat ventricular cardiomyocytes. The rats of As₂O₃ group were treated with 0.8 mg·kg^-1·d^-1 As₂O₃ intravenously for 7 days consecutively and the control group with saline. The ECG was recorded to calculate heart rate-corrected QT interval (QTc). Single cardiomyocytes were isolated by using collagenase II, and the action potential duration (APD) and ion currents were recorded by whole-cell patch clamp. [Ca²⁺]_>i was examined by confocal laser scanning microscopy. Our data showed that both QTc and APD were prolonged significantly after As₂O₃treatment. Meanwhile, As₂O₃ suppressed I _K1 and shifted the reversal potential to more positive direction. Moreover, the density of I _Ca,L was augmented significantly, and the steady-state activation curve became more negative, whereas, the inactivation and reactivation of I _Ca,L were not changed notably after As₂O₃ administration. Furthermore, the maximal [Ca²⁺] _i was enhanced obviously by either KCl or caffeine stimulation in As₂O₃-treated cardiomyocytes. Our results show that the potential mechanism of As₂O₃-induced QT interval prolongation in rat might be relative to disturbing the fine balance of transmembrane currents ( increasing I _Ca,L and decreasing I _K1) and causing APD prolongation.

ObjectiveThe study was performed to compare the 3D pharyngeal airway dimensions in adult skeletal Class II patients with different vertical growth patterns (low, normal, and high angle) and to investigate whether the upper airway dimensions of untreated skeletal Class II adults were affected by vertical skeletal variables.MethodsCone-beam computed tomography (CBCT) records of 64 untreated adult skeletal Class II patients (34 male and 30 female) were collected to evaluate the pharyngeal airway dimensions. Subjects were divided into three subgroups according to the GoGn-SN angle (low angle, normal angle or high angle). All subgroups were matched for sex. ANOVA and SNK - q tests were used to identify differences within and among groups (p<0.05). Coefficient of product-moment correlation (Pearson correlation coefficient) was used to analyze the association between pharyngeal airway dimensions and vertical growth patterns.ResultsThe results showed that pharyngeal airway measurements were statistically significantly less (p<0.05) in high angle group as compared to normal angle or low angle group.ConclusionsAdult skeletal Class II subjects with vertical growth patterns have significantly narrower pharyngeal airways than those with normal or horizontal growth patterns, confirming an association between pharyngeal airway measurements and a vertical skeletal pattern.

No abstract