Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

BackgroundThe role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear.MethodsSixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups.ResultsThe wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups.ConclusionTNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.     

亚急性期脑卒中康复过程中半球间皮质结构可塑性差异

探讨脑卒中患者亚急性期康复过程中不同半球间皮质结构可塑性机制差异。     

Cargo-laden erythrocyte ghosts target liver mediated by macrophages

Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or ¹⁸F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked ¹⁸F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease.     

丹皮酚对去卵巢骨质疏松大鼠叉头框蛋白O3a/Wnt信号通路及椎骨密度的影响

背景:丹皮酚可抑制炎症,减轻慢性骨关节炎临床症状,作为一种不良反应小、更为安全的天然药物成分,探讨其对骨质疏松症的治疗作用具有重要的临床意义。目的:探究丹皮酚对去卵巢骨质疏松大鼠叉头框蛋白O3a(forkhead box O3a,FoxO3a)/Wnt信号通路及椎骨密度的影响。方法:雌性SD大鼠随机分为6组,每组10只。假手术组仅切除卵巢旁部分脂肪组织;其余50只大鼠均采用双侧卵巢摘除法制备去卵巢骨质疏松大鼠模型,模型制备成功后分为模型组、雌激素组[炔雌醇10μg/(kg·d)]、丹皮酚低、中、高剂量组[丹皮酚125,250,500 mg/(kg·d)],每组10只,灌胃给药;假手术组、模型组灌胃等量生理盐水,持续干预12周。ELISA法测定血清雌激素、骨保护素、骨钙素水平;采用双能X射线动物骨密度测定仪检测大鼠股骨及椎骨骨密度;采用骨科生物力学测试仪检测大鼠股骨及椎骨生物力学指标:弹性模量、最大载荷、屈服载荷;实时荧光定量PCR检测椎骨组织FoxO3a、Wnt2 mRNA表达水平;免疫印迹法检测椎骨组织FoxO3a、Wnt2及核内β-catenin蛋白表达。结果与结论:①治疗后,与假手术组比较,模型组L4,5骨密度、弹性模量、最大载荷、屈服载荷、血清雌二醇、骨保护素水平、椎骨组织Wnt2 mRNA及蛋白水平、核内β-catenin蛋白水平均显著降低(P<0.05),骨钙素水平、椎骨组织FoxO3a mRNA及蛋白水平显著增加(P<0.05);②与模型组比较,丹皮酚低、中、高剂量组大鼠L4,5骨密度、弹性模量、最大载荷、屈服载荷、血清雌二醇、骨保护素水平、椎骨组织Wnt2 mRNA及蛋白水平、核内β-catenin蛋白水平依次增加(P<0.05),血清骨钙素水平、椎骨组织FoxO3a mRNA及蛋白水平依次降低(P<0.05),且丹皮酚高剂量组均优于雌激素组(P<0.05);③提示丹皮酚可增加去卵巢骨质疏松大鼠椎骨骨密度,改善其骨生物力学状况,减轻骨质疏松,该作用可能与抑制FoxO3a、促进Wnt2/β-catenin通路激活有关。     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

咽后壁瓣修复术后并发阻塞性睡眠呼吸暂停的临床研究

探讨腭裂术后腭咽闭合不全（VPI）患者行咽后壁瓣修复术（PFS）后阻塞性睡眠呼吸暂停（OSA）的发生率及严重程度，并探讨手术年龄对OSA发生率及严重程度的影响。     

Spermatorrhea in a Chinese patient with temporal lobe epilepsy: a case report

Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Sexual dysfunction has been reported in patients with seizure, which mostly manifests as erectile dysfunction and premature ejaculation in men. In this study, we report the case of a 65-year-old Chinese man with frequent spermatorrhea. Electroencephalography suggested local epilepsy in the left temporal lobe. After treatment with anti-epilepsy drugs, the symptoms disappeared and did not recur. To the best of our knowledge, this is the first reported case of epilepsy-induced spermatorrhea. The symptoms of spermatorrhea are probably a rare manifestation of seizure. When repetitive stereotyped symptoms occur, seizure should be considered, and tentative anti-epileptic treatment may be a good option.     

Coinfection by Talaromyces marneffei and Mycobacterium abscessus in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibody: a case report

Patients with anti-interferon (IFN)-γ autoantibodies have weakened immune defenses against intracellular pathogens. Because of its low incidence and non-specific symptoms, diagnosis of anti-IFN-γ autoantibody syndrome is difficult to establish during the early stages of infection. Here, we report a patient with high titers of serum anti-IFN-γ autoantibodies suffering from opportunistic infections. The patient presented with intermittent fever for 2 weeks. During his first hospitalization, he was diagnosed with Talaromyces marneffei pulmonary infection and successfully treated with antifungal therapy. However, multiple cervical lymph nodes subsequently became progressively enlarged. Mycobacterium abscessus infection was confirmed by positive cervical lymph node tissue cultures. High-titer serum anti-IFN-γ antibodies were also detected. Following anti-M. abscessus therapy, both his symptoms and lymph node lymphadenitis gradually improved. Anti-IFN-γ autoantibody syndrome should be considered in adult patients with severe opportunistic coinfections in the absence of other known risk factors.     

Sudden sensorineural hearing loss during pregnancy: etiology,treatment, and outcome

ObjectiveTo analyze the etiologies, treatments, and outcomes of sensorineural hearing loss (SSNHL) during pregnancy.Study designRetrospective chart review of 25 pregnant patients treated for SSNHL between January 2012 and September 2019. Forty-nine age matched non-pregnant women with severe and profound hearing loss diagnosed with SSNHL during the same period served as controls. Data were recorded on age, symptoms, onset of hearing loss, audiometric results, treatments, and outcomes.ResultsThe mean age was 29.6 years (range 23–38 years). Intratympanic steroids (ITS) were administered in 15 (60.0%) pregnant women with SSNHL. Three women were treated with postauricular steroids only, while another woman was treated with intravenous ginkgo leaf extract and dipyridamole. The remaining six women received no medications. More than half (8/15, 53.3%) of pregnant women with SSNHL receiving ITS experienced hearing improvement. Pregnant women with profound hearing loss who received no medication had no hearing improvement. Most pregnant women with SSNHL (12/15, 80.0%) had higher fibrinogen levels than controls (mean values 3.77±0.71 g/L and 2.54±0.48 g/L, respectively).ConclusionFibrinogen could be a risk factor for SSNHL during pregnancy. ITS may benefit pregnant women with severe and profound SSNHL.