The impact of COPD and smoking history on the severity of COVID-19: A systemic review and meta-analysis

Comorbidities are associated with the severity of coronavirus disease 2019 (COVID-19). This meta-analysis aimed to explore the risk of severe COVID-19 in patients with pre-existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history. A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The languages of literature included English and Chinese. The point prevalence of severe COVID-19 in patients with pre-existing COPD and those with ongoing smoking was evaluated with this meta-analysis. Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study. The pooled OR of COPD and the development of severe COVID-19 was 4.38 (fixed-effects model; 95% CI: 2.34-8.20), while the OR of ongoing smoking was 1.98 (fixed-effects model; 95% CI: 1.29-3.05). There was no publication bias as examined by the funnel plot and Egger's test (P = not significant). The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID-19. COPD and ongoing smoking history attribute to the worse progression and outcome of COVID-19.     

Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects

Background: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)‐7‐like cytokine that triggers dendritic cell‐mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL‐7 receptor alpha (IL‐7Rα) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4⁺ T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen‐induced late‐phase reaction (LPR) in atopic subjects. Methods: Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR⁺ DC in skin LPR. RT‐PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Results: Allergen‐induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR⁺ and CD11c⁺ cells infiltrated relatively late (24–48 h). The majority of TSLPR⁺ cells were DC co‐expressing blood DC antigen‐1 (BDCA‐1) or BDCA‐2. Freshly isolated blood DC expressed both TSLPR and IL‐7Rα chains. Maturation and stimulation with TSLP or polyriboinosinic–polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL‐7Rα chains in DC but not in chemoattractant receptor‐homologous molecule expressed on Th2 cells⁺ CD4⁺ T cells. Conclusion: The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2‐type T cells in allergic inflammation.     

碳纳米管对树突状细胞成熟和T细胞分化作用研究

Th分化在免疫应答过程中起着关键性的作用,主要由树突状细胞来调控。碳纳米管是由碳元素组成的空心管状纳米材料,可作为抗原载体。碳纳米管对树突状细胞和Th分化的影响是决定其免疫响应的关键因素。分析氧化多壁碳纳米管(CNT)对小鼠骨髓来源的树突状细胞(BMDCs)功能的影响,以及对过敏抗原多肽OVA_323-339的 Th1和Th2免疫反应的影响。实验结果显示,BMDCs大量吞噬CNT,但对其细胞表面活化标志分子CD86、MHCII以及细胞因子TNF-α表达没有明显变化。CNT/抗原复合物可促进BMDCs表面MHCII的表达和CD8⁺T细胞增殖,增殖细胞的比例由28.7%分别增加到40.6%、41.3%和29.6%。Th2型细胞因子IL-4、IL-13和IL-10的表达和CD4⁺T的增殖受到抑制,增殖细胞的比例由54.4%减少到38.9%、46.6%和39.8%。研究结果提示,CNT不影响DCs的成熟和活化,但CNT可以影响过敏抗原的Th分化平衡,可抑制Th2型细胞因子的表达,促进Th1型免疫响应。     

切除嗅球对成年大鼠嘴侧迁移流的影响

我们以前的研究观察到嗅球切除后室管膜下层(SVZ)仍能产生新细胞,但新细胞迁移的通路尚不清楚。为此,本研究建立了成年SD雄性大鼠右侧嗅球切除模型,利用Nissl染色、PSA-NCAM和GFAP免疫组织化学染色的方法观察了成年SD大鼠嗅球切除后存活不同时间两侧嘴侧迁移流(RMS)的形态学特征及RMS细胞的密度和单个细胞的面积,并进行统计学分析;同时利用Westernblot方法检测PSA-NCAM在RMS的表达。结果观察到:(1)嗅球切除后不同时间点,嗅球切除侧RMS的细胞数和面积增加,PSA-NCAM免疫阳性细胞数增加,而GFAP免疫阳性细胞数在嗅球切除后2周和4周有明显增加;(2)嗅球切除后两侧RMS的细胞密度和单个细胞的面积没有明显改变;(3)从矢状切片可见嗅球切除后RMS的形态和路径没有明显改变,但在切除断端细胞堆积明显。这些结果提示嗅球切除后仍有年轻神经元沿RMS向嘴侧迁移,SVZ的神经生发活动与嗅球的存在与否可能没有必然的联系。     

The posterior groove as a landmark for location of the palatovaginal canal in axial computed tomography

Purpose

To investigate use of posterior groove of palatovaginal (PV) canal as an anatomic landmark in determining the location of PV canal in axial computed tomography (CT) images of pterygopalatine fossa (PPF).

Methods

A total of 20 skull specimens were examined in this analysis. Each skull was scanned by CT with and without a probe inserted through PV canal to measure the anatomic structures. CT images of 70 patients were used for comparing the rate of correct location of PV canal between the conventional method (using the vidian canal as a landmark) and the method of using the posterior groove as a landmark. Two skulls were dissected using endoscopy to further reveal the advantage of the posterior groove as a landmark.

Results

In all 20 skull specimens, the groove showed the morphology of a narrow groove and elliptical fossa in 24 and 16 sides, respectively. In CT images, the angle from PV canal and the posterior groove to the hard palate was 53.14° ± 5.48° and 20.93° ± 6.28°, respectively, which was significantly different (P ≤ 0.05). The rate of correct location of PV canal was statistically significantly higher with the method of posterior groove as a landmark than the conventional method (70.7 vs 49.3 %, P < 0.05). The endoscopic anatomy of the posterior groove and its use in locating the PV canal were described.

Conclusion

The posterior groove can be used as an anatomic landmark in correctly locating PV canal in the axial CT image of the PPF.

     

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical–cortical connectivity after preterm delivery.     

Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization

Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a co-receptor for growth factors and chemokines and is a molecular marker associated with the epithelial–mesenchymal transition during development and carcinogenesis. In this study, we generated two specific mouse anti-human CD138 monoclonal antibodies (mAbs, clone ID: 480CT5.4.3, 587CT7.3.6.5) using hybridoma technology and identified their immunological characteristics. After hybridoma sequencing, the single-chain variable fragments (ScFvs) cloned from two hybridoma cells were combined with anti-CD3 OKT-3 ScFv to generate two recombinant bispecific antibodies (h-STL002, m-STL002) against CD138 and CD3 molecules, respectively. The bispecific antibodies were able to specifically target CD138?+?multiple myeloma (MM) cells and CD3?+?T cells, and showed the potent cytotoxicity against MM RPMI-8226 cell line through T cell activation. However, these bispecific antibodies without T cells did not cause toxic side effect on MM cells. Overall, the two hybridoma clones and their bispecific formats have great potential to promote diagnosis and immunotherapy of plasma cell malignancy.     

Second-harmonic imaging of cornea after intrastromal femtosecond laser ablation

Nonlinear laser scanning microscopy is widely used for noninvasive imaging in cell biology and tissue physiology. However, multiphoton fluorescence imaging of dense, transparent connective tissue (e.g., cornea) is challenging since sophisticated labeling or slicing is necessary. High-resolution, high-contrast second harmonic generation (SHG) imaging of corneal tissue based on the intrinsic structure of collagen is discussed. The three-dimensional corneal ultrastructure in depths up to hundreds of microns can be probed noninvasively, without any staining or mechanical slicing. As an important application of second harmonic imaging in ophthalmology, the modification of corneal ultrastructure using femtosecond laser intrastromal ablation is systematically investigated to evaluate next-generation refractive surgical approaches.     

视网膜母细胞瘤基因对人骨肉瘤细胞株OS732的影响

目的 观察外源性N端截短的视网膜母细胞瘤（Rb)基因对骨肉瘤细胞株OS732的生长和细胞间缝隙连接信息通讯能力的影响。方法 构建N端截短的长度为1.65kb Rb基因的真核表达质粒,并用DOTAP将其导入骨肉瘤细胞株OS732。应用逆转录－聚合酶链反应（RT－PCR）和Northern blot检测Rb基因的表达;用细胞计数,流式细胞仪分析和软琼脂克隆形成试验观察OS732细胞的生成状况;用半定量RT－PCR法和罗氏黄荧光传输法检测细胞间缝隙连接信息通讯的能力。结果 转染N端截短的Rb基因后,OS732细胞内可检测到内源性和外源性Rb基因的mRNA表达。OS732细胞的形态发生改变,其生长速度减慢,软琼脂形成集落能力降低,细胞周期阻滞于G0－G1期;缝隙连接蛋白基因Gonnexin43的表达和细胞信息通讯能力增强。结论 N端截短的Rb基因可抑制骨肉瘤细胞株OS732的恶性生长表型以及增强细胞间信息通讯能力。