Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

AKR7A3在肺腺癌中异常表达及临床意义

目的:探讨醛-酮还原酶家族7成员A3（AKR7A3）在肺腺癌中的异常表达及与临床病理特征的关系，并探究其临床意义。方法:采用生物信息学数据库分析、免疫组化、Western Blot、Real-time PCR等方法对肺腺癌组织及不同细胞中AKR7A3的表达进行检测与分析。结果:Oncomine数据库分析结果显示，在肺腺癌中，AKR7A3的表达普遍高于正常肺组织，分别为正常肺组织的1.811倍（P=0.022）、1.356倍（P<0.01）、1.413倍（P=0.002）。Kaplan-Meier Plotter数据库分析结果显示，AKR7A3高表达的患者较低表达的患者生存时间缩短，差异具有统计学意义（P=0.003 7）。免疫组化染色显示肺腺癌组织中AKR7A3的表达较癌旁增高，在与临床病理特征的相关性分析中，发现其与肿瘤分化程度（P<0.01）、淋巴结转移情况（P=0.029）以及TNM分期（P<0.01）相关，且会造成患者生存时间缩短（P=0.031）。Cox多因素分析表明AKR7A3可能是影响肺腺癌患者预后的独立危险因素(P=0.012)。Western Blot及Real-time PCR实验提示不同肺腺癌细胞中AKR7A3蛋白及mRNA表达普遍增高。结论:AKR7A3在肺腺癌中表达增高，对预后有不良影响，有促进肿瘤发生发展的作用。     

The emerging role of ultrasound in detecting interstitial lung disease in patients with rheumatoid arthritis

ObjectiveTo investigate the potential role of US in the detection of ILD in a cohort of patients with RA.MethodsPatients with diagnosis of RA were consecutively enrolled. All patients underwent pulmonary examination, laboratory data, DLCO measure, chest HRCT and radiographs, and US examination. A healthy group was included as control group. US was performed according the 14-intercostal space scanning protocol using the following semiquantitative scale [0 = normal (≤ 5 B-lines); 1 = slight (≥ 6 and ≤ 15 B-lines); 2 = moderate, (≤ 16 and ≥ 30 B-lines); 3 = severe (≥ 30 B-lines)].ResultsA total of 74 RA patients and 74 healthy controls were included. Thirty of 74 patients (40.5%) showed US signs of ILD with respect to the healthy controls (3 subjects, 4.1%) (P < 0.001); whereas HRCT showed ILD in 27 (36.4%) of 74 patients. Among the 30 patients that showed US findings of ILD, 17 (56.6%) were asymptomatic from respiratory view-point. The sensitivity and specificity of US were 92% and 89% respectively. A positive correlation between US and HRCT findings were found (P < 0.001) whereas no correlation was found with chest radiographs and DLCO findings. Positive association between US findings and DAS28-ESR, anti-CCP and RF (P < 0.01 for each respectively) was found. Feasibility, represented by the mean time spent to perform the pulmonary US assessment was 7.8 minutes (± SD 1.2, range 6 to 10 minutes).ConclusionsOur results support the potential of US in detect accurately ILD in patients with RA and provide a rationale to consider it as a friendly screening tool to be implemented in early phases of the disease.     

Prenatal stress‐related alterations in synaptic transmission and 5‐HT7 receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT7 receptor antagonist SB 269970

Early life adversity exerts a detrimental influence on developing brain neuronal networks and its consequences may include mental health disorders. In rats, prenatal stress may lead to anxiety and depressive‐like behavior in the offspring. Several lines of evidence implicated an involvement of prenatal stress in alterations of the brain serotonergic system functions, but the effects of prenatal stress on its core, the dorsal raphe nucleus (DRN), still remain incompletely understood. The present study was aimed at finding whether prenatal stress induces modifications in the glutamatergic and GABAergic inputs to DRN projection cells and whether it affects DRN 5‐HT₇ receptors, which modulate activity of these synapses. Prenatal stress resulted in an increase in basal frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in a decrease in basal frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from putative projection neurons in DRN slices ex vivo. While there were no changes in the excitability of DRN projection neurons, the 5‐HT₇ receptor‐mediated reduction in the sEPSC frequency and rise in the sIPSC frequency, seen in control rats, were largely absent in slices obtained from prenatally stressed rats. Repeated administration of SB 269970, a 5‐HT₇ receptor antagonist, resulted in a reversal of prenatal stress‐induced alterations in 5‐HT₇ receptor‐mediated effects on the sEPSC/sIPSC frequency. Moreover, the treatment reversed prenatal stress‐induced alterations in basal excitatory transmission and partially reversed the effect of stress on basal inhibitory transmission in the DRN.     

改良跗骨窦入路治疗 SandersⅡ～Ⅲ 型跟骨骨折疗效分析

目的探讨改良跗骨窦入路与传统跗骨窦入路治疗 SandersⅡ～Ⅲ 型跟骨骨折的近期临床疗效。方法选取 2015 年 1 月—2017 年 8 月符合选择标准的 53 例 SandersⅡ～Ⅲ 型跟骨骨折患者，采用随机数字表法将患者分为观察组（21 例，采用从腓骨长短肌腱下方暴露距下关节后对骨折复位的改良跗骨窦入路）和对照组（32 例，采用传统跗骨窦入路）。两组患者性别、年龄、侧别、致伤原因、骨折分型、受伤至手术时间以及术前 Böhler 角、Gissane 角、疼痛视觉模拟评分（VAS）等一般资料比较差异均无统计学意义（P>0.05），具有可比性。记录并比较两组患者手术时间、术后引流量、手术相关并发症，术后 Böhler 角、Gissane 角及术后角度改善值；并使用 VAS 评分、美国矫形足踝协会（AOFAS）踝与后足评分及简明健康调查量表（SF-36 量表）评价疗效。 结果53 例患者均顺利完成手术，无血管神经损伤、围手术期死亡等严重并发症。两组患者手术时间及术后引流量比较差异无统计学意义（P>0.05）。两组患者均获随访，随访时间 12～36 个月，平均 17 个月。术后未发生骨折移位、内固定失败、骨折畸形愈合等；所有患者均未行二期关节融合手术。两组骨折愈合时间比较差异无统计学意义（t=0.30，P=0.77）。两组术后 2 d Böhler 角、Gissane 角均较术前显著改善（P<0.05）；但观察组术后 2 d Böhler 角、Gissane 角及改善值与对照组比较差异均无统计学意义（P>0.05）。两组术后 24 h 及 1 年 VAS 评分均较术前显著改善（P<0.05）；术后 24 h 及 1 年两组 VAS 评分比较差异均无统计学意义（P>0.05）。两组术后 1 年 AOFAS 评分比较差异无统计学意义（t=1.46，P=0.15）；但观察组术后 1 年 SF-36 量表评分显著高于对照组（t=2.08，P=0.04）。末次随访时，观察组 2 例、对照组 8 例患者出现距下关节僵硬或疼痛，两组发生率比较差异无统计学意义（χ²=1.98，P=0.16）。 结论采用改良跗骨窦入路治疗 SandersⅡ～Ⅲ 型跟骨骨折，具有创伤小、直视下复位清晰、复位固定可靠、切口并发症少等优点。     

MSCs来源外泌体在创面修复中的研究进展

目的总结近年来 MSCs 来源外泌体（exosomes，EXOs）在创面修复中的研究进展。方法广泛查阅国内外有关 MSCs-EXOs 在创面修复中作用的文献，总结分析 MSCs-EXOs 在创面修复过程中的作用机制及其临床应用前景。结果MSCs-EXOs 在创面愈合过程中可抑制早期的炎性反应，促进血管新生和上皮细胞的增殖与迁移，后期调控胶原合成并抑制瘢痕增生。与 MSCs 相比，MSCs-EXOs 具有高稳定性、易于储存、不易致瘤、无需增殖、便于定量使用等优点，有着广阔的临床应用前景。结论MSCs-EXOs 能够促进创面修复，且有希望发展成为临床上一种促进急性或慢性创面修复的产品。