IMPORTANCEFor patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. OBJECTIVE To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke.DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020).INTERVENTIONS A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. MAIN OUTCOMES AND MEASURESThe primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was −10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. RESULTSThe trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, −5.1% to ϱ)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, −0.8%; 95% CI, −7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, −0.5%; 95% CI, −10.3% to 9.2%).CONCLUSIONS AND RELEVANCE Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold.

Objectives:To retrospectively describe our 10-year experience with extracranial non-vestibular head and neck schwannomas by presenting their clinical features, diagnostic methods, surgical decisions, and treatment outcomes.Methods:This is a retrospective study conducted at the Department of Otolaryngology, Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Shanghai First People’s Hospital, Shanghai, China. The medical records of 46 patients diagnosed with schwannoma in the extracranial head and neck region as confirmed on paraffin-embedded sections from January 2003 to December 2012 were reviewed.Results:All tumors were benign, and 52% presented as asymptomatic palpable solitary masses. Compressive symptoms, which can represent meaningful indicators of the nerve of origin were commonly noted. The most common nerve of origin was the brachial plexus (n=13, 28.3%).Conclusion:While postoperative histopathologic examination is still the gold standard, fine needle aspiration cytology, CT scan, and magnetic resonance imaging may be useful in the diagnosis of schwannomas. As schwannomas are radioresistant, and as, despite their benign nature, can cause severe secondary symptoms, the best treatment of choice is complete excision with preservation of functions.

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Premature senescence is a key process in the progression of diabetic nephropathy (DN). Premature senescence of renal tubular epithelial cells (RTEC) in DN may result from the accumulation of damaged mitochondria. Mitophagy is the principal process that eliminates damaged mitochondria through PTEN-induced putative kinase 1 (PINK1)-mediated recruitment of optineurin (OPTN) to mitochondria. We aimed to examine the involvement of OPTN in mitophagy regulation of cellular senescence in RTEC in the context of DN. In vitro, the expression of senescence markers P16, P21, DcR2, SA-β-gal, SAHF, and insufficient mitophagic degradation marker (mitochondrial P62) in mouse RTECs increased after culture in 30 mM high-glucose (HG) conditions for 48 h. Mitochondrial fission/mitophagy inhibitor Mdivi-1 significantly enhanced RTEC senescence under HG conditions, whereas autophagy/mitophagy agonist Torin1 inhibited cell senescence. MitoTempo inhibited HG-induced mitochondrial reactive oxygen species and cell senescence with or without Mdivi-1. The expression of PINK1 and OPTN, two regulatory factors for mitophagosome formation, decreased significantly after HG stimulation. Overexpression of PINK1 did not enhance mitophagosome formation under HG conditions. OPTN silencing significantly inhibited HG-induced mitophagosome formation, and overexpression of OPTN relieved cellular senescence through promoting mitophagy. In clinical specimens, renal OPTN expression was gradually decreased with increased tubulointerstitial injury scores. OPTN-positive renal tubular cells did not express senescence marker P16. OPTN expression also negatively correlated with serum creatinine levels, and positively correlated with eGFR. Thus, OPTN-mediated mitophagy plays a crucial regulatory role in HG-induced RTEC senescence in DN. OPTN may, therefore, be a potential antisenescence factor in DN.

Background MicroRNAs (miRNAs or miRs) serve crucial roles in the progression of osteoporosis. This study investigated the role and specific molecular mechanism of miR-135-5p in regulating osteoblast differentiation and calcification. Methods Bone morphogenetic protein 2 (BMP2) was employed to interfere with the differentiation of MC3T3-E1. Then, miR-135-5p mimic or miR-135-5p inhibitor was transfected into MC3T3-E1, and quantitative RT-PCR was used to measure the expression of miR-135-5p. The expressions of runt-related transcription factor 2 (Runx2), osterix (OSX), osteopontin (OPN), and osteocalcin (OCN) were determined using western blot. Alkaline phosphatase (ALP) activity was measured using an appropriate kit assay. Calcium nodule staining was evaluated with alizarin red staining. A luciferase reporter assay was used to verify the target of miR-135-5p. Hypoxia-inducible factor 1 α inhibitor (HIF1AN) overexpression was applied to investigate its own role in the mechanism and a miR-135-5p rescue experiment was also performed. Results Overexpression of miR-135-5p promoted osteogenic differentiation and calcification, as shown by the increase in ALP activity, calcification and osteogenic marker levels, including Runx2, OSX, OPN and OCN. Knockdown of miR-135-5p yielded the opposite results. HIF1AN was confirmed as a direct target of miR-135-5p. HIF1AN overexpression inhibited osteogenic differentiation and calcification while miR-135-5p reversed these effects. Conclusions These results indicate that miR-135-5p might have a therapeutic application related to its promotion of bone formation through the targeting of HIF1AN.

Background and Purpose: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion. Methods: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0–4 versus 5–7 versus 8–10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days. Results: In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30–14.48] and 3.20 [1.68–6.09]; respectively) and lower mortality (60.8% versus 77.6%, P =0.005 and 35.0% versus 66.2%, P< 0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94–1.02]). Conclusions: Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT. REGISTRATION: URL: http://www.chictr.org.cn . Unique identifier: ChiCTR1800014759.

In conclusion, the PEEK interbody fusion cage containing CS/DBM or AIB following one- or two-level discectomy had a similar outcome for cervical spondylotic radiculopathy and/or myelopathy. The rate of fusion and the recovery rate of JOA score between the two groups were the same. The filling of CS/DBM in the PEEK cage instead of AIB has the advantage of less operative blood loss and fewer complications at the donor site.

Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury.