Third‐party Tolerogenic Dendritic Cells Reduce Allo‐reactivity In vitro and Ameliorate the Severity of Acute graft‐Versus‐host Disease in Allo‐bone Marrow Transplantation

Tolerogenic dendritic cells (tDCs) potently induce and maintain tolerance based on their distinct characteristics compared with conventional DCs. Recent reports show that donor or host tDCs promote allograft survival in mice. In this study, the efficacy of third‐party tDCs in the prevention of acute graft‐versus‐host disease (aGVHD) was evaluated. In vitro, tDCs derived from the bone marrow (BM) of D1 mice were induced by GM‐CSF, IL‐10 and TGF‐β1. The phenotypes, expression of cytokines and suppression of tDCs were analysed. In vivo, the effects of adoptive transfer of third‐party‐tDCs were evaluated in an MHC‐mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathological specimens and serum cytokines were analysed in tDC‐treated mice and untreated controls. Tolerogenic DCs had low expression of MHC and co‐stimulatory molecules, expressed high levels of ‘immunosuppressive’ cytokines and suppressed allo‐CD4⁺T cell proliferation. In the B6→D2 mouse model, all aGVHD mice died within 18 days. Fortunately, third‐party tDCs transferred at low doses (10⁴) effectively prolonged survival after allo‐BMT. Furthermore, in the mice treated with 10⁴ tDCs, serum levels of IL‐10/TGF‐β were significantly higher and the percentage of Foxp3⁺ cells continually increased compared with the mice treated with other doses of tDCs. Third‐party tDCs play a crucial role in reducing the severity of aGVHD by modulating the secretion of various cytokines and expanding Foxp3⁺ regulatory T cells, which suggests the possibility of using third‐party tDCs for therapeutic applications. Furthermore, special attention should be paid to the optimal range of tDCs for preventing allograft rejection.     

职业性有机溶剂中毒15例临床表现和影像学特征分析

目的 探讨职业性有机溶剂中毒的临床表现、神经影像学特征、治疗及预后。方法 回顾性分析15例职业性有机溶剂中毒患者的临床资料。结果 15例患者均急性或亚急性起病,有明确的有机溶剂职业接触史,主要临床表现包括头晕(73.3%)、认知功能下降(60%)、锥体束损害(53.3%)、颅内高压综合征(46.7%)、意识障碍(33.3%); 其中14例患者头颅磁共振成像(Magnetic resonance imaging,MRI)显示为弥漫性脑组织肿胀,以双侧大脑半球白质为主,呈“火焰状”,10例累及双侧基底节(苍白球),8例累及双侧小脑齿状核,呈“肾形”改变,5例累及双侧丘脑; 所有患者使用脱水剂、糖皮质激素及高压氧等综合治疗后,其中12例患者好转出院,无或仅遗留轻微后遗症,3例患者无明显改善,预后差。结论 职业性有机溶剂中毒以头晕、认知功能下降、锥体束损害、颅内高压综合征及意识障碍等中毒性脑病表现为主,典型头颅MRI为双侧大脑半球白质、苍白球及小脑齿状核对称性病变,结合患者职业接触史需考虑本病; 早期、长程、足量给予脱水剂、糖皮质激素及高压氧等综合治疗,大多数患者预后良好。     

黄芪多糖对阿尔茨海默病大鼠神经细胞活性、认知功能及Caspase-9表达水平的影响

目的 探讨黄芪多糖(Astragalus polysacharin,APS)对阿尔茨海默病(Alzheimer’s disease,AD)大鼠神经细胞活性、认知功能及天冬氨酸特异性半胱氨酸蛋白酶(Cysteinyl aspartate specific protease,Caspase)-9表达水平的影响。方法 36只无特定病原体(Specific pathogen free, SPF)级美国斯泼累格·多雷(Sprague Dawley)雌雄各半的大鼠,按照随机数字表分为6组,正常组、AD组、药物对照组、干预A组、干预B组及干预C组; 除正常组外,其余大鼠建立AD大鼠模型; 建模后药物对照组采用0.5 g/kg的吡拉西坦灌胃,干预A组、干预B组及干预C祖均采用0.2、0.4及0.8 g/kg的黄芪多糖(Astragalus polysacharin,APS)灌胃,正常组及AD组灌胃等剂量的生理盐水,均1次/d,灌胃时间连续60 d。采用Morris水迷宫实验观察认知功能; 苏木精-伊红(Hematoxy lin-Eosin,HE)染色观察海马组织病理学表现; 末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法[Terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling,TUNEL]法检测神经细胞凋亡率; 免疫印迹及实时定量聚合酶链反应(Quantitatie real time polymerase chain reaction,QRT-PCR)技术分别检测细胞色素C(Cytochrome c,Cyt-c),Caspase-3及Caspase-9蛋白及信使核糖核酸(Messenger RNA,mRNA)相对表达水平。结果 与正常组比较,AD组大鼠灌胃后第1～5 d的逃避潜伏期均延长(P<0.05); 与AD组比较, 干预A组、干预B组、干预C组逃避潜伏期均缩短(P<0.05),药物对照组逃避潜伏期与干预C组比较无明显差异(P>0.05)。与正常组比较,AD组大鼠游泳距离增加(P<0.05); 与AD组比较,干预A组、干预B组及干预C组大鼠游泳距离均减少(P<0.05),干预C组与药物对照组相似(P>0.05)。正常组海马结构完成,神经元排列紧密,细胞核清晰且无空泡; AD组大鼠海马组织结构紊乱,神经元数目减少,细胞核深染,细胞膜收缩及部分消失; APS干预组及药物对照组神经元排列较AD组整齐有序,肿胀程度减轻,细胞核较清晰。各组大鼠海马组织神经细胞凋亡率比较有明显差异(F=134.900,P<0.001); 与正常组比较,AD组神经细胞凋亡率升高(P<0.05); 与AD组比较,干预A组、干预B组及干预C组神经细胞凋亡率降低(P<0.05),药物对照组与干预C组神经细胞凋亡率相似(P>0.05)。与正常组比较,AD组海马组织Cyt-C,Caspase-3及Caspase-9蛋白及mRNA 相对表达水平上调(P<0.05); 与AD组比较,不同水平干预组海马组织Cyt-C,Caspase-3及Caspase-9蛋白及mRNA 相对表达水平下调(P<0.05),药物对照组与干预C组上述蛋白及mRNA相对表达水平相似(P>0.05)。结论 黄芪多糖能够改善AD大鼠认知功能,减轻海马组织病理损伤,抑制神经元凋亡且呈现水平依赖性,其机制可能与抑制Cyt-C及caspase-3/9信号通路有关。     

人工智能技术在创伤救治中的应用及研究进展

创伤引起的多发伤致残率和致死率高,救治难度大但目前创伤救治的医疗模式仍然存在不足,创伤患者的救治面临巨大挑战。人工智能(AI)是基于机器学习、强化学习和深度学习等基础算法的智能技术,现已应用于创伤患者的救治工作中,其高效精准的计算机视觉、规划决策以及大数据统计分析等技术方向既提高了创伤患者救治的安全性和效率,同时也降低了临床医师的工作负荷,弥补了传统创伤救治模式的不足。笔者对AI在创伤急诊分诊、诊断、治疗及战创伤预防等方面的应用及研究进展进行综述,为AI的临床应用提供参考。     

PFNA置入位点设计对股骨粗隆间骨折患者疗效及安全性的影响

目的 探讨不同置入位点对股骨粗隆间骨折(IFF)患者股骨近端防旋髓内钉(PFNA)手术有效性及安全性的影响.方法 回顾性分析2015年3月—2018年11月常州市金坛区人民医院收治IFF患者122例,男性85例,女性37例;年龄60～79岁,平均70.1岁.按手术方式不同分为定位点内移组(63例)和PFNA组(59例).PFNA组行传统PFNA进针点置入髓内钉,定位点内移组则由传统PFNA定位点内移0.5～0.8cm置入髓内钉.比较两组患者围手术期指标、髓内钉一次置入成功率、术中透视次数,随访6个月采用Harris髋关节功能评分评价两组患者髋关节功能,并记录并发症情况.结果 两组患者住院时间和首次负重时间比较差异无统计学意义(P>0.05);定位点内移组手术时间、术中出血量、术中透视次数、骨折愈合时间均显著少于PFNA组[(63.55±17.81)min vs.(82.74±20.66)min、(41.22±12.69)mL vs.(63.58±14.59)mL、(5.13±1.77)次vs.(7.26±1.58)次、(4.12±1.33)个月vs.(5.14±1.27)个月,P<0.05].定位点内移组导针一次性置入成功率显著高于PFNA组(96.83％vs.84.75％),组间比较差异均有统计学意义(P<0.05).随访6个月,两组患者髋关节Harris评分优良率(93.65％vs.94.92％)比较差异无统计学意义(P>0.05).定位点内移组出现内固定物松动、断裂、螺旋刀片切割股骨头、髋内翻、骨折移位等并发症比例与PFNA组比较差异无统计学意义(P>0.05).结论 在PFNA术中将传统定位点内移0.5～0.8cm能够提高髓内钉一次性置入成功率,缩短手术时间,减少出血,避免术中多次透视,安全可靠.     

Sleep,sedentary activity,physical activity,and cognitive function among older adults: The National Health and Nutrition Examination Survey, 2011–2014

ObjectivesWe aimed to estimate the association of sleep, sedentary activity and physical activity with cognitive function among older adults, with consideration of the competing nature between variables of activity status.DesignCross-sectional study.MethodsA total of 3086 older adults (60 years or older) in the 2011–2014 National Health and Nutrition Examination Survey were included. The Global Physical Activity Questionnaire was used to measure self-reported time for sedentary activity, walking/bicycling and moderate-to-vigorous physical activity (MVPA). Cognitive function was examined using the CERAD Word Learning subtest (memory), Digit Symbol Substitution Test (executive function/processing speed), and Animal Fluency Test (language). Sleep duration was obtained via interview. Isotemporal substitution models using multivariable linear regression were applied to examine the associations of replacing sleep, sedentary activity, walking/bicycling, MVPA with each other and cognitive function, stratified by sleep duration per night (≤7 h, >7 h).ResultsAmong participants with sleep duration ≤7 h/night, replacing 30 min/day of sedentary activity with 30 min/day of MVPA or 30 min/day was associated with better cognition. Among participants with sleep duration >7 h/night, replacing 30 min/day of sleep with 30 min/day of sedentary activity, walking/bicycling, or MVPA was associated with better cognition.ConclusionsReplacing sedentary activities with MVPA was associated with favorable cognitive function among older adults sleeping no longer than 7 h/night, and replacing excessive sleep with sedentary or physical activities was associated with favorable cognition. Future research is expected to examine the associations of replacing different activity status on long-term cognitive outcomes in longitudinal studies.     

Sevoflurane Combined with ATP Activates Caspase-1 and Triggers Caspase-1-Dependent Pyroptosis in Murine J774 Macrophages

Sevoflurane is one of the most commonly used volatile anesthetics. Recent studies have shown that sevoflurane plays an important role in modulation of inflammation and immunity. However, little is known about the related molecular mechanisms. This study was designed to investigate the effects and mechanisms of sevoflurane on inflammatory cell death pyroptosis in the murine macrophage cell line J774 cells. Sevoflurane combined with ATP could increase the level of activated caspase-1, pyroptosis, and reactive oxygen species (ROS). Furthermore, treatment of cells with the caspase-1 inhibitor Ac-YVAD-CMK dramatically decreased the percentage of pyroptosis. In addition, inhibition of ROS with N-acetyl-l-cysteine or diphenyleneiodonium significantly reduced the activated levels of caspase-1. These results demonstrated that sevoflurane combined with ATP could activate caspase-1 and trigger caspase-1-dependent pyroptosis through the modulation of ROS production.     

Interstitial telomeric repeats are enriched in the centromeres of chromosomes in Solanum species

Interstitial telomeric repeats (ITRs) were reported in a number of animal and plant species. Most ITRs are organized as short tandem arrays and are likely evolutionary relics derived from chromosomal rearrangements and DNA repairs. However, megabase-sized ITR arrays were reported in Solanum species. Here, we report a fluorescence in situ hybridization (FISH) survey of ITRs in all representative diploid Solanum species, including potato, tomato, and eggplant. FISH revealed massive amplification of ITRs in the centromeric regions of chromosomes from the Solanum species containing the B and P genomes. A significant proportion of the ITR FISH signals was mapped within the primary constrictions of the pachytene chromosomes of Solanum pinnatisectum (B genome). In addition, some ITR sites overlapped with St49, a satellite repeat enriched in centromeric DNA sequences associated with CENH3 nucleosomes, in both A and B genome Solanum species. These results show that some ITR subfamilies have been amplified and invaded in the functional centromeres of chromosomes in Solanum species.     

Community Workers’ Social Support and Sleep Quality during the Coronavirus Disease 2019 (COVID-19): A Moderated Mediation Model

To explore the relationship between social support and sleep quality of community workers in Wuhan during the coronavirus disease 2019 (the COVID-19 infection epidemic), this research constructed a mediating effect model to explore the mediating psychological mechanism of social support influencing sleep quality of front-line community workers. A total of 500 front-line community workers in Wuhan were investigated. We used the perceived social support scale (PSSS), the Connor-Davidson Resilience Scale (CD-RISC), the perceived stress scale (PSS), and the Pittsburgh sleep quality index (PSQI) to measure social support, psychological resilience, perceived stress and sleep quality. Specifically, the higher the PSQI, the worse the sleep quality. Pearson correlation structural equation model was used to analyze the relationship between these factors. The results showed that: (1) There was a significant negative correlation between social support, psychological resilience, and perceived stress of community workers and PSQI, that means, the higher the level of social support, psychological resilience, and perceived stress, the higher the sleep quality. (2) Social support positively predicted psychological resilience and perceived stress, and perceived stress negatively predicted PSQI. (3) Social support can affect sleep quality through the mediating role of psychological resilience and perceived stress, and the mediating role includes two paths: the single mediating role of perceived stress and the chain mediating role of psychological resilience-perceived stress. (4) Gender moderates the relationship between social support and perceived stress, and the influence of social support on perceived stress of women is higher than that of men. Gender moderates the relationship between psychological resilience and PSQI, and only women’s psychological resilience had a negatively predictive effect on PSQI, while men did not, which means that psychological resilience of female frontline community workers can positively predict sleep quality. This research reveals the relationship between social support and sleep quality and its mechanism and verifies that social support can indirectly affect physical health through psychological resilience and perceived stress. It provides reference suggestions and intervention guidance for improving the sleep quality of community workers.