间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景*

当前因SARS-CoV-2感染而引起的2019新型冠状病毒肺炎(COVID-19)肆虐全球,严重危害人类健康。SARS-CoV-2感染性强,危重症患者死亡率高,尽管各种各样的治疗正在进行临床试验,但目前尚无有效的治疗方法。间充质干细胞(mesenchymal stem cell,MSC)在临床前试验中对多种疾病有良好的治疗效果,因而受到了广泛地关注。MSC可能利用分化潜能诱导分化成功能性肺样细胞、免疫调节与免疫细胞互作、抑制炎症来降低促炎细胞因子分泌、迁移和归巢靶向损伤肺部、抗病毒作用来减少肺上皮细胞中的病毒复制、产生细胞外囊泡来修复受损的组织,进而使COVID-19患者肺功能逐渐恢复正常,缓解并达到治疗COVID-19的目的。综合讨论了COVID-19的基本特征和当前主要治疗手段,同时总结了MSC在COVID-19中的临床研究和当前面临的挑战,探讨了MSC治疗COVID-19的应用前景,为MSC在COVID-19中的治疗提供了理论基础和现实依据。     

间充质干细胞在新型冠状病毒肺炎治疗中的研究现状

新型冠状病毒肺炎(COVID-19)由新型冠状病毒(SARS-CoV-2)导致,可发生严重肺部损伤甚至死亡,目前为止仍在全球范围内广泛蔓延。SARS-CoV-2感染依赖于血管紧张素转换酶2(ACE2)和Ⅱ型跨膜丝氨酸蛋白酶,可导致机体免疫紊乱,促发炎症风暴从而损伤靶器官。COVID-19目前尚无特效药物,间充质干细胞(MSCs)具有组织修复和免疫调节等功能,而且在流感病毒相关性肺炎及其他肺疾病中有一定疗效,因此可能是治疗COVID-19潜在有效药物。目前部分研究也显示出积极的治疗效果,而具体的疗效仍需进一步的临床研究来验证。     

新型冠状病毒的结构基础与新型冠状病毒肺炎的临床药物治疗

新型冠状病毒肺炎(corona virus disease 2019, COVID-19)是指由新型冠状病毒(severe acute respiratory syndrome coronavirus2, SARS-CoV-2)感染导致的肺炎。SARS-CoV-2结合细胞表面受体——血管紧张素转化酶2 (angiotensin-converting enzyme 2,ACE2)感染肺部细胞,导致白细胞浸润,血管和肺泡壁通透性增加,肺表面活性物质减少,引起呼吸系统症状。局部的炎症加重引起细胞因子风暴,造成全身性炎症反应综合征。2019年12月,武汉市卫生健康委员会报告了多例新型肺炎,分离并确定了病原体SARS-CoV-2。截至2020年9月13日,全世界216个国家或地区受累,2 860余万人确诊COVID-19,90余万人死于该疾病,病死率高达3.20%。到目前为止,尚无特效药物可治疗COVID-19,因此解析病毒结构,探索治疗药物显得尤其重要。本文总结了SARS-CoV-2的病毒结构和COVID-19的临床药物治疗,并分析了他们之间可能的相关性。     

NK细胞免疫治疗防治COVID-19应用潜力的研究进展

新型冠状病毒肺炎(corona virus disease 2019, COVID-19)作为一种新发型急性呼吸道传染病,目前已对全球公共卫生安全构成严重威胁。严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染导致COVID-19重症患者淋巴细胞减少、淋巴细胞功能障碍并引起不可控的炎症反应。由于自然杀伤细胞(natural killer cell, NK细胞)在抗病毒和免疫调节中具有重要作用,以NK细胞为基础的免疫治疗可能是有效抗击COVID-19的治疗策略之一。现就已发表的SARS-CoV-2临床研究报告,整理介绍了该病毒的基本特征及COVID-19患者的主要免疫病理学状态,阐述NK细胞在抗病毒领域的潜在作用机制与研究进展,并对NK细胞防治COVID-19的免疫治疗策略及所面临的问题与挑战作一综述。     

2019冠状病毒病对肺外系统的影响及可能机制探讨

2019冠状病毒病(coronavirus disease 2019,COVID-19)是由严重急性呼吸综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)导致的感染性疾病。SARS-CoV-2感染人体后除作用于肺部的SARS-CoV-2功能受体外,还可以作用于心脏、消化道、肝脏、肾脏、中枢系统的SARS-CoV-2功能受体,引起肺外脏器的损伤,诱发多器官功能衰竭,增加COVID-19的病死率。但目前对SARS-CoV-2引起肺外各脏器损伤的具体作用机制还不是很清楚,需要更多临床和实验室数据支持。通过检索COVID-19相关的文献,对SARS-CoV-2导致的肺外系统影响及其可能作用机制作一综述。     

益生菌缓解新型冠状病毒感染症状的研究进展

由急性呼吸道综合征冠状病毒2(severeacuterespiratorysyndromecoronavirus2,SARS-CoV-2)引起的新型冠状病毒感染(coronavirusdisease2019,COVID-19)从2020年初迅速扩展至全球,成为人类历史上最严重的大流行之一。已有证据证明当SARS-CoV-2的刺突蛋白(S蛋白)与细胞表面受体血管紧张素转化酶2 (angiotensin converting enzyme 2, ACE2)结合时,可感染宿主细胞,引起肠道菌群失调,并引发不同的并发症。益生菌是活的微生物,已被证明对人体健康有益。因其在调节肠道菌群、治疗多种疾病和抗病毒方面的功效而被考虑用来改善COVID-19。本文基于目前公开的临床前和临床试验结果,总结了益生菌在缓解COVID-19临床症状及胃肠道不良反应的效果,并讨论了益生菌在改善COVID-19后遗症方面的潜力,从而为后续管理COVID-19提供新的方向,进一步为呼吸系统疾病提供理论依据。     

COVID-19确诊病例居住环境病毒检测结果分析及防控探讨

新型冠状病毒肺炎(COVID-19)传播速度快、感染范围广,其感染方式主要是聚集性感染,感染途径主要是呼吸道飞沫和接触传播。了解环境中,特别是COVID-19确诊病人生活环境中的病毒存在情况,是做好环境消毒,阻断新型冠状病毒(SARS-CoV-2)传播的重要步骤,对COVID-19防控具有重要意义。本研究旨在探讨COVID-19患者生活环境中SARS-CoV-2的存在情况,从SARS-CoV-2存在的空间部位、病毒核酸含量、消毒效果等方面对SARS-CoV-2的相关特点做出初步研究,为制定有效的SARS-CoV-2防控措施提供科学依据。本研究以COVID-19病例治疗前的3个家庭居住环境和治疗出院后隔离期间的2个宾馆居住环境中采集的样本为研究材料,采用RT-PCR方法检测样本中的SARS-CoV-2核酸并进行比较分析。结果显示,首次从3个家庭环境中采样48份,RTPCR检测SARS-CoV-2核酸阳性5份(10.42%),3个家庭的环境样本中均有阳性样本检出。首次采样48h后在家庭3进行第二次采样16份,SARS-CoV-2核酸检测阳性2份(12.5%),检测Ct值比首次升高。家庭3消毒后24h采集的16份样本SARS-CoV-2核酸检测均为阴性,并且两处宾馆环境采集的24份样本SARS-CoV-2核酸检测也均为阴性。本研究提示,COVID-19病例的生活环境中可以检出SARS-CoV-2,病毒存在区域、存在物品、病毒核酸含量均有差异;对外环境进行消毒可以达到消毒目的,能够起到阻断SARS-CoV-2传播的防控效果。     

严重急性呼吸综合征冠状病毒2的预存免疫

新型冠状病毒肺炎(corona virus disease 2019, COVID-19)由严重急性呼吸综合征冠状病毒2 (severe acute respiratory syndrome-coronavirus 2, SARS-CoV-2)感染引起,临床表现多样。近来,在未感染SARS-CoV-2的人群检测出了SARS-CoV-2特异性记忆CD4~+、CD8~+ T细胞和能识别SARS-CoV-2的抗体,这揭示了人群中存在SARS-CoV-2的预存免疫。这种预存免疫可由4种人冠状病毒(human coronavirus, HCoVs)感染诱导。这些HCoVs是季节性感冒的致病因子,其抗原表位和SARS-CoV-2有广泛的同源性。HCoV诱导的SARS-CoV-2的预存免疫可影响SARS-CoV-2感染的发生和COVID-19症状的轻重。该发现有助于SARS-CoV-2感染的血清学检测方法的改进和SARS-CoV-2疫苗的升级换代。     

SARS-CoV-2与SARS-CoV:病原学、流行病学、临床与病理

2019年12月在武汉暴发了由SARS-CoV-2感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19),并迅速扩散至全国.SARS-CoV-2和SARS冠状病毒(SARS-CoV)都属于套式病毒目、冠状病毒科、冠状病毒属中的SARS相关冠状病毒种,本文总结了两者在来源、病毒结构、流行病学、临床表现和病理学特征等方面的差异,以期更全面认识SARS-CoV和SARS-CoV-2,为COVID-19的防治研究提供帮助.     

严重急性呼吸综合征冠状病毒诊断标志物动态变化及检测方法的研究进展

2019-冠状病毒病(coronavirus disease 2019, COVID-19)在全球范围内流行,患者出现严重急性呼吸系统疾病,传染性高于2003年暴发的严重急性呼吸综合征(severe acute respiratory syndrome, SARS)。COVID-19严重影响了人类的健康,同时引起了人们的恐慌。因此,快速、精准地诊断COVID-19患者,阻断病毒快速传播至关重要,但是在COVID-19诊断中存在早期漏检和后期复阳等情况。现综述严重急性呼吸综合征冠状病毒(severe acute respiratory syndrome coronavirus, SARS-CoV)感染后各标志物的动态变化及检测意义,并将其与严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)进行比较,以期为SARS-CoV-2等冠状病毒的高效诊断提供借鉴。     

Distribution of N,P, K,Ca, Mg,S, Zn,Fe, Mn and Cu in groundnut

Summary Concentration of N, P, K, Ca, Mg and S in summer groundnut crop was higher than in kharif while Zn, Fe, Mn and Cu contents were higher in summer crop. Kernel's N, P and Zn; Leaflet's Ca and Mn; Stem's K and Fe; Root's S and Cu and Petiole's Mg contents were highest. Shell's N, P, K, Mg, S, Zn and Cu; Kernel's Ca, Fe and Mn contents were the least. N, P, K, S, Zn and Cu concentrations decreased linearly as the crop grew. Ca, Mg, Fe and Mn concentrations did not display any distinct pattern. Ca concentration was positively correlated with pod yield in both the seasons.     

Simultaneous measurement of the trace elements Al, As, B, Be, Cd, Co, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se, Sr, and Zn in human serum and their reference ranges by ICP-MS

The goal of this article was to establish reference ranges of the concentration of trace elements in human serum and to compare these results with those reported by other authors. We describe the sample preparation and measurement conditions that allow the rapid, precise, and accurate determination of Al, As, B, Be, Cd, Co, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se, Sr, and Zn in human serum samples (n=110) by inductively coupled plasma-mass spectrometry (ICP-MS). Accuracy and precision were determined by analyzing three reconstituted reference serum samples by comparison with other methods and by the standard addition procedure. The advantages of the ICP-MS method include short time of analysis of the elements mentioned, low detection limit, high precision, and high accuracy. Disadventages include a high risk of contamination due to the presence of some of the elements of interest in the environment, the relatively delicate sample handling, and the high cost of the equipment.     

Reference values for the concentrations of As,Cd, Co,Cr, Cu,Fe, I,Hg, Mn,Mo, Ni,Pb, Se,and Zn in selected human tissues and body fluids

This report attempts to formulate reference ranges of elemental concentrations for 15 trace elements in selected human tissues and body fluids. A set of samples consisting of whole blood, blood serum, urine, milk, liver, and hair were chosen and considered for 15 elements of biological significance: As, Cd, Co, Cr, Cu, F, Fe, I, Hg, Mn, Mo, Ni, Pb, Se, and Zn. The results represent wholly or partially data received from 40 countries of the global regions of Africa, Asia, Europe, North, South, and Central America, Australia, and New Zealand. This survey, even if qualitative, has been useful in demonstrating certain trends of trace-element scenarios around the world. It is of course recognized that both diet and environment exert a strong influence on the distribution pattern of several elements, such as As, Cd, Mn, Pb, Se, and Zn. A limited comparison of the available information on soil status of different countries reflected some interesting associations for elements, such as Mn and Zn. Importantly, this study revealed that only a few countries were in a position to identify a reasonable amount of data on samples requested for this project. Regretably, for a number of countries, any dependable data for even such essential elements as Cu, Fe, and Zn were not available. In view of the nutritional importance of many elements, the time is ripe for concerted efforts by intergovernmental agencies to initiate investigations or commission task forces/projects to generate reliable reference data for selected global regions, which sadly lack data of any kind at present.     

Crystal structure, detonation performance, and thermal stability of a new polynitro cage compound: 2, 4, 6, 8, 10, 12, 13, 14, 15-nonanitro-2, 4, 6, 8, 10, 12, 13, 14, 15-nonaazaheptacyclo [5.5.1.13, 11. 15, 9] pentadecane

A new polynitro cage compound 2, 4, 6, 8, 10, 12, 13, 14, 15-nonanitro-2, 4, 6, 8, 10, 12, 13, 14, 15-nonaazaheptcyclo [5.5.1.1(3,11).1(5,9)] pentadecane (NNNAHP) was designed in the present work. Its molecular structure was optimized at the B3LYP/6-31 G(d,p) level of density functional theory (DFT) and crystal structure was predicted using the Compass and Dreiding force fields and refined by DFT GGA-RPBE method. The obtained crystal structure of NNNAHP belongs to the P-1 space group and the lattice parameters are a = 9.99 ?, b = 10.78 ?, c = 9.99 ?, α = 90.01°, β = 120.01°, γ = 90.00°, and Z = 2, respectively. Based on the optimized crystal structure, the band gap, density of state, thermodynamic properties, infrared spectrum, strain energy, detonation characteristics, and thermal stability were predicted. Calculation results show that NNNAHP has detonation properties close to those of CL-20 and is a high energy density compound with moderate stability.     

Monovalent Cation Permeation through the Connexin40 Gap Junction Channel : Cs,Rb, K,Na, Li,TEA, TMA,TBA, and Effects of Anions Br,Cl, F,Acetate, Aspartate,Glutamate, and NO3

The unitary conductances and permeability sequences of the rat connexin40 (rCx40) gap junction channels to seven monovalent cations and anions were studied in rCx40-transfected neuroblastoma 2A (N2A) cell pairs using the dual whole cell recording technique. Chloride salt cation substitutions (115 mM principal salt) resulted in the following junctional maximal single channel current-voltage relationship slope conductances (γ_j in pS): CsCl (153), RbCl (148), KCl (142), NaCl (115), LiCl (86), TMACl (71), TEACl (63). Reversible block of the rCx40 channel was observed with TBA. Potassium anion salt γ_j are: Kglutamate (160), Kacetate (160), Kaspartate (158), KNO₃ (157), KF (148), KCl (142), and KBr (132). Ion selectivity was verified by measuring reversal potentials for current in rCx40 gap junction channels with asymmetric salt solutions in the two electrodes and using the Goldman-Hodgkin-Katz equation to calculate relative permeabilities. The permeabilities relative to Li⁺ are: Cs⁺ (1.38), Rb⁺ (1.32), K⁺ (1.31), Na⁺ (1.16), TMA⁺ (0.53), TEA⁺ (0.45), TBA⁺ (0.03), Cl⁻ (0.19), glutamate⁻ (0.04), and NO₃− (0.14), assuming that the monovalent anions permeate the channel by forming ion pairs with permeant monovalent cations within the pore thereby causing proportionate decreases in the channel conductance. This hypothesis can account for why the predicted increasing conductances with increasing ion mobilities in an essentially aqueous channel were not observed for anions in the rCx40 channel. The rCx40 effective channel radius is estimated to be 6.6 Å from a theoretical fit of the relationship of relative permeability and cation radius.     

Relations of the Al,B, Ba,Br, Ca,Cl, Cu,Fe, K,Li, Mg,Mn, Na,P, S,Si, Sr,and Zn mass fractions to morphometric parameters in pediatric and nonhyperplastic young adult prostate glands

The variation with age of the 18 trace element mass fractions and some histological characteristics of intact prostate glands of 50 subjects aged 0–30 years was investigated by instrumental neutron activation analysis, inductively coupled plasma atomic emission spectrometry, and a quantitative morphometric analysis. Mean values ± standard error of the mean (M ± SΕΜ) for the mass fractions (in milligrams per kilogram wet tissue) of these trace elements in pre-puberty were: Al 28.5 ± 9.0, B 0.40 ± 0.11, Ba 1.48 ± 0.44, Br 10.5 ± 1.5, Ca 241 ± 30, Cl 3,203 ± 278, Cu 3.51 ± 0.89, Fe 33.7 ± 4.1, K 2,364 ± 145, Li 0.020 ± 0.004, Mg 153 ± 23, Mn 0.46 ± 0.06, Na 2,286 ± 130, P 1,391 ± 100, S 1,698 ± 132, Si 62 ± 11, Sr 0.38 ± 0.08, and Zn 27.6 ± 2.3. During puberty and postpuberty, when there is a significant increase in circulating androgens, the mean values were: Al 7.2 ± 1.4, B 0.21 ± 0.05, Ba 0.25 ± 0.06, Br 5.8 ± 1.0, Ca 433 ± 81, Cl 2,314 ± 201, Cu 1.77 ± 0.13, Fe 20.9 ± 1.6, K 2,585 ± 118, Li 0.0088 ± 0.0014, Mg 232 ± 27, Mn 0.34 ± 0.04, Na 1,875 ± 107, P 1,403 ± 98, S 1,673 ± 73, Si 22.2 ± 3.1, Sr 0.22 ± 0.03, and Zn 93.3 ± 8.9. Mean values (M ± SΕΜ) of percent volumes (%) of the stroma, epithelium and lumen in the prostate before puberty were 73.4 ± 2.6, 20.4 ± 1.7, and 4.45 ± 0.94, respectively, versus 46.5 ± 2.5, 38.5 ± 1.9, and 14.9 ± 1.2 during puberty and postpuberty. This work’s results confirm that the Zn mass fraction in prostate tissue is an androgen-dependent parameter. For the first time it has been demonstrated that the glandular lumen is a main pool of Ca, Mg, and Zn accumulation and that the stroma is a main pool of Al, B, Ba, Br, Cl, Cu, Fe, Mn, Na, and Si accumulation in the normal human prostate, for the age range 0–30 years. It was concluded that the Ca, Mg, and Zn binds tightly within the prostatic fluid, because the volume of glandular lumen reflects the volume of prostatic fluid.     

Competitive inhibition and selectivity enhancement by Ca in the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, Hf) by carrot (Daucus carota cv. U.S. harumakigosun)

We investigated the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, and Hf) and the effect of Ca on their uptake in carrots (Daucus carota cv. U.S. harumakigosun) by the radioactive multitracer technique. The experimental results suggested that Na, Mg, K, and Rb competed for the functional groups outside the cells in roots with Ca but not for the transporter-binding sites on the plasma membrrane of the root cortex cells. In contrast, Y, Ce, Pm, and Gd competed with Ca for the transporters on the plasma membrane. The selectivity, which was defined as the value obtained by dividing the concentration ratio of an elemental pair, K/Na, Rb/Na, Be/Sr, and Mg/Sr, in the presence of 0.2 and 2 ppm Ca by that of the corresponding elemental pair in the absence of Ca in the solution was estimated. The selectivity of K and Rb in roots was increased in the presence of Ca. The selectivity of Be in roots was not affected, whereas the selectivity of Mg was increased by Ca. These observations suggest that the presence of Ca in the uptake solution enhances the selectivity in the uptake of metabolically important elements against unwanted elements.     

The Effect of Age and Gender on Al, B, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, S, Sr, V, and Zn Contents in Rib Bone of Healthy Humans

The effect of age and gender on major, minor, and trace element contents in the intact rib bone of 80 relatively healthy 15–55-year-old women and men was investigated. Contents or upper limit of contents of 16 chemical elements in the rib bone were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Mean values (M?±?SΕΜ) for the mass fraction of Ba, Ca, Cu, Fe, K, Li, Mg, Na, P, S, Sr, and Zn (milligram per kilogram of dry bone) were as follows: 2.54?±?0.16, 171,400?±?4,050, 1.35?±?0.22, 140?±?11, 1,874?±?71, 0.049?±?0.011, 2,139?±?38, 5,378?±?88, 75,140?±?1,660, 1,881?±?51, 291?±?20, and 92.8?±?1.5, respectively. The upper limits of contents of Al, B, Mn, and V were <7.20, <0.65, <0.36, and <0.03, respectively. Statistically significant tendency for the Ca, Mg, and P content to decrease with age was found in the human rib bone, regardless of gender. The mass fraction of Fe in the male rib bone increases with age. It was shown that higher Ca, Mg, Na, P, and Sr mass fractions as well as lower Fe content were typical of female ribs as compared to those in male ribs.