Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.     

An indirect comparison meta-analysis of noninvasive intravesical instillation and intravesical injection of botulinum toxin-A in bladder disorders

International Urology and Nephrology - Botulinum toxin type A (BTX-A) intravesical instillation and BTX-A intravesical injection are both effective treatments or overactive bladder (OAB) and...     

Correction to: Correlation between lordosis distribution index,lordosis tilt,and occurrence of proximal junctional kyphosis following surgery for adult degenerative scoliosis

European Spine Journal -     

Subconjunctival Injection of Regulatory T Cells Potentiates Corneal Healing Via Orchestrating Inflammation and Tissue Repair After Acute Alkali Burn

PurposeThis study aimed to investigate the therapeutic effects and underlying mechanisms of locally delivered regulatory T cells (Tregs) on acute corneal wound healing after alkali burn.MethodsAfter corneal alkali burn, the mice were injected subconjunctivally with regulatory T cells (Tregs) isolated from syngeneic mice. The wound healing process was monitored by clinical manifestation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). As amphiregulin (Areg) was significantly upregulated, its reparative function in injured corneas was suggested. The hypothesis was further verified via loss- and gain-of-function experiments by administrating the antibody of Areg (anti-Areg) and recombinant Areg (rmAreg).ResultsSubconjunctivally injected Tregs rapidly migrated to injured corneas. The mice treated with Tregs showed prominently reduced corneal opacity, alleviated edema, and faster re-epithelialization compared with the control group. Mechanistically, Treg treatment led to suppressed infiltration of inflammatory cells, along with improved proliferation and inhibited apoptosis of corneal epithelial cells. Tregs expressed upregulated functional markers, including Areg. Expectantly, the levels of Areg in corneas were dramatically higher in the Treg injection group, in line with better corneal restoration. Additional experiments showed that the administration of anti-Areg blunted the reparative effect of Tregs, while exogenous Areg enhanced it. Treg-treated corneas also exhibited less neovascularization and fibrosis at a later reconstruction stage of corneal repair.ConclusionsThe findings showed that the subconjunctival injection of Tregs effectively promoted corneal wound healing by inhibiting excessive inflammation and enhancing epithelial regeneration, with an indispensable reparative role of Areg. Subsequent complications of corneal vascularization and fibrosis were therefore reduced.     

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P = .481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.     

外周静脉置管疼痛评分与腹腔镜肾切除术患者术后疼痛程度的相关性

目的 探讨外周静脉置管疼痛评分与腹腔镜肾切除术患者术后疼痛程度的相关性。
方法 选择择期行腹腔镜肾切除手术的患者106例,男57例,女49例,年龄18～65岁,BMI 18～28 kg/m²,ASA Ⅰ或 Ⅱ级。术前采用20 G留置针于手背浅表静脉进行置管操作并记录患者对此操作的VAS评分。所有患者于全麻下手术,术后给予舒芬太尼静脉自控镇痛。记录患者术后24 h内静息时最高VAS评分和活动时最高VAS评分,术后24 h内镇痛泵有效按压次数、术后24 h内舒芬太尼的额外消耗量。
结果 外周静脉置管VAS评分与术后24 h内静息时最高VAS评分（r_s=0.64,P＜0.001）、术后24 h内活动时最高VAS评分（r_s=0.65,P＜0.001）、术后24 h内镇痛泵有效按压次数（r_s=0.59,P＜0.001）、术后24 h内舒芬太尼额外消耗量（r_s=0.58,P＜0.001）呈明显正相关。外周静脉置管VAS评分≥2.0分的患者中术后静息时出现中重度疼痛的例数为14例（33.3%）,VAS评分＜2.0分的患者中为8例（12.5%）,VAS评分≥2.0分的患者术后出现中重度疼痛的比例明显高于VAS评分＜2.0分的患者（P＜0.05）。
结论 术前外周静脉置管疼痛评分与腹腔镜肾切除术患者术后疼痛程度具有相关性,外周静脉置管VAS评分≥2.0分患者中术后24 h内静息时出现中重度疼痛比例高于VAS评分＜2.0分患者。