Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd,Iran

HLA-G is supposed to play a pivotal role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. A 14-bp insertion and/or deletion polymorphism in exon-8 has a possible role in HLA-G expression. The present study analyzed the 14-bp insertion/deletion polymorphism in normal pregnancy and recurrent miscarriage patients in order to discover a possible correlation between the 14-bp polymorphism and recurrent miscarriage (RM). In this study, genomic DNA from 200 RM patients and 200 normal fertile control individuals using the routine salting out method were isolated. Exon-8 of HLA-G gene of the two groups were amplified using polymerase chain reaction and analyzed by electrophoresis on 10% non-denaturing polyacrylamide gel electrophoresis containing ethidium bromide and visualized under ultraviolet light. HLA-G allele frequencies and genotypes in RM women and the fertile control group were compared using a Chi-square test. The results showed that there was a difference in allelic frequencies of 14-bp insertion polymorphism between fertile controls and RM patients; the frequency of +14 bp/?14?bp heterozygotes was significantly higher in RM patients as compared with fertile controls. Furthermore, the frequency of +14-bp insertion allele was significantly higher in those with RM as compared with normal fertile controls. From the findings here, it was concluded that a 14-bp insertion/deletion polymorphism in exon 8 could play a possible role in recurrent miscarriages. These results might ultimately be of significance for clinicians and those involved in understanding infertility and RM.     

正常妊娠和原因不明习惯性流产者HLA-G基因14 bp缺失多态性研究

为研究HLA-G基因3’非翻译区14 bp缺失多态性在习惯性流产患者和正常妊娠妇女中的差异,分别提取患者蜕膜和正常女性外周血DNA。PCR扩增HLA-G基因第8外显子,产物经9%非变性聚丙烯酰胺凝胶电泳分离,并经EB染色后在凝胶成像仪下观察。显著性检验用SAS软件包进行四格表χ2分析。结果显示:(1)-14 bp和+14 bp等位基因频率在两组间无显著性差异;(2)与正常对照组相比,RSA患者组中-14 bp/+14 bp杂合子的比例显著升高(χ2=4.7690,P=0.0290)。结果提示,中国人群HLA-G 14 bp缺失多态性在维持正常的妊娠中可能有重要作用。     

The management of coronavirus disease 2019 (COVID-19)

In December 2019, a novel coronavirus causing severe acute respiratory disease occurred in Wuhan, China. It is an emerging infectious disease with widespread and rapid infectiousness. The World Health Organization declared the coronavirus outbreak to be a public health emergency of international concern on 31 January 2020. Severe COVID-19 patients should be managed and treated in a critical care unit. Performing a chest X-ray/CT can judge the severity of the disease. The management of COVID-19 patients includes epidemiological risk and patient isolation; treatment entails general supportive care, respiratory support, symptomatic treatment, nutritional support, psychological intervention, etc. The prognosis of the patients depends upon the severity of the disease, the patient's age, the underlying diseases of the patients, and the patient's overall medical condition. The management of COVID-19 should focus on early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control.     

The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective

2019 novel coronavirus (SARS-CoV-2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID-19). However, SARS-CoV-2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID-19 in China to better understand the transmission and diagnosis regarding this infectious disease.     

Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test

Coronavirus disease (COVID-19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID-19 diagnoses, we developed an IgM-IgG combined assay and tested it in patients with suspected SARS-CoV-2 infection. In total, 56 patients were enrolled in this study and SARS-CoV-2 was detected by using both IgM-IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM-IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM-IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID-19.     

2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan,China

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.     

Peripheral HLA-G/ILT-2 immune checkpoint axis in acute and convalescent COVID-19 patients

The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) can elicits pro-viral activities by down-modulating immune responses. We analysed soluble forms of HLA-G, IL-6 and IL-10 as well as on immune effector cell expression of HLA-G and its cognate ILT-2 receptor in peripheral blood obtained from hospitalised and convalescent COVID-19 patients. Compared with convalescents (N = 202), circulating soluble HLA-G levels (total and vesicular-bound molecules) were significantly increased in hospitalised patients (N = 93) irrespective of the disease severity. During COVID-19, IL-6 and IL-10 levels were also elevated. Regarding the immune checkpoint expression of HLA-G/ILT-2 on peripheral immune effector cells, the frequencies of membrane-bound HLA-G on CD3+ and CD14+ cells were almost identical in patients during and post COVID-19, while the frequency of ILT-2 receptor on CD3+ and CD14+ cells was increased during acute infection. A multi-parametric correlation analysis of soluble HLA-G forms with IL-6, IL-10, activation markers CD25 and CD154, HLA-G, and ILT-2 expression on immune cells revealed a strong positive correlation of soluble HLA-G forms with membrane-bound HLA-G molecules on CD3+/CD14+ cells only in convalescents. During COVID-19, only vesicular-bound HLA-G were positively correlated with the activation marker CD25 on T cells. Thus, our data suggest that the elevated levels of soluble HLA-G in COVID-19 are due to increased expression in organ tissues other than circulating immune effector cells. The concomitant increased expression of soluble HLA-G and ILT-2 receptor frequencies supports the concept that the immune checkpoint HLA-G/ILT-2 plays a role in the immune-pathogenesis of COVID-19.     

Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis

We tested the possible association of the 14-bp polymorphism of the HLA-G gene in the course of two inflammatory diseases, rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Patients and controls were genotyped for the 14-bp polymorphism by polymerase chain reaction with specific primers for the exon 8 of the human leukocyte antigen (HLA)-G gene and the amplified fragment was visualized in a 6% polyacrylamide gel. A total of 106 JIA patients, 265 RA patients, 356 healthy adults and 85 healthy children were genotyped for the 14-bp polymorphism. Female JIA patients presented a higher frequency of the -14 bp allele when compared with female healthy children (0.743 and 0.500, corrected P=0.003), which reflected in the JIA group as a whole. This increased frequency of the -14-bp allele was observed in all JIA subtypes. In RA patients, no differences in allelic and genotypic frequencies were observed between patients and controls. No correlations were observed among genotype and disease severity or clinical manifestations. Our data suggest that the HLA-G -14 bp allele is probably a risk factor for JIA, mainly in females. Considering the differences observed in relation to gender, we suggest that hormonal differences can interfere with the development of JIA. Considering the RA patients, our data agree with results from the literature and highlight the differences in the etiology of RA and JIA.     

Meta-analysis of the relationship between 14bp insertion/deletion polymorphism of HLA-G gene and susceptibility to systemic lupus erythematosus

We performed a meta-analysis to examine the relationship between the human leukocyte antigen-G (HLA-G) 14 base pairs sequence (14bp) insertion (ins)/deletion (del) polymorphism to systemic lupus erythematosus (SLE). Eligible studies were extracted in PubMed, Embase, Cochrane Library and CNKI (Chinese) up to March 31, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the strength of the association. Finally, 7 studies with 1864 cases and 2259 controls were involved in this meta-analysis. Overall, the HLA-G 14bp ins/del polymorphism was significantly associated with SLE susceptibility (ins vs. del: OR = 1.179, 95%CI = 1.037–1.341, P = 0.012; ins/ins vs. del/del: OR = 1.394, 95%CI = 1.153–1.684, P = 0.001; ins/del vs. del/del: OR = 1.199, 95%CI = 1.041–1.382, P = 0.012; ins/ins + ins/del vs. del/del: OR = 1.252, 95%CI = 1.097–1.430, P = 0.001). When stratified by ethnicity, significance was found in Asians (ins/ins vs. del/del: OR = 1.326, 95%CI = 1.001–1.756, P = 0.049) and Caucasians (ins/ins vs. del/del: OR = 1.454, 95%CI = 1.126–1.878, P = 0.004; ins/del vs. del/del: OR = 1.288, 95%CI = 1.051–1.579, P = 0.015; ins/ins + ins/del vs. del/del: OR = 1.340, 95%CI = 1.106–1.623, P = 0.003). Our results suggest that the HLA-G 14bp insertion allele might act as an increased risk against SLE. Besides, this is the first meta-analysis to report an association between the HLA-G 14bp ins/del polymorphism and SLE. Larger and well-designed studies are needed to further confirm these findings.     

Evaluation of serum soluble HLA-G levels post-recovery from COVID-19 and post-vaccination (Sinopharm and Pfizer-BioNTech)

Serum soluble HLA-G (sHLA-G) levels have been shown to be upregulated in COVID-19 patients. In this study, sHLA-G levels were examined in COVID-19 patients 14–21 days post-recovery (100 patients) and 80 uninfected controls. In addition, individuals vaccinated with Sinopharm or Pfizer-BioNTech (50 individuals each) were followed 21 days post-first dose and 21 days post-second dose. Serum sHLA-G levels were significantly higher in recovered patients than in controls. The first and second doses of Sinopharm and Pfizer-BioNTech were associated with significantly elevated levels of sHLA-G compared to controls or recovered patients, except for the first dose of Pfizer-BioNTech where sHLA-G levels did not show significant differences compared to recovered patients. In conclusion, recovery from COVID-19, as well as vaccination with two doses of Sinopharm or Pfizer-BioNTech, were associated with up-regulated levels of sHLA-G molecules, but the first dose of Sinopharm had the greatest effect in raising sHLA-G levels.     

CD-sACE2 inclusion compounds: An effective treatment for coronavirus disease 2019 (COVID-19)

Coronaviruses are common human viruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV), the middle east respiratory syndrome coronavirus and the SARS-CoV-2. Coronaviruses mainly bind to transmembrane receptor proteins on the human cell membrane through spike proteins (S-proteins), thus releasing the RNA of the virus into the interior of the host cell to cause an infection. In this article, we discuss the mechanism and production of cyclodextrin-soluble angiotensin-converting enzyme 2 (CD-sACE2) inclusion compounds in the treatment of SARS-CoV-2 infections by blocking S-proteins. On the basis of the current research evidence, we believe that CD-sACE2 inclusion compounds have the potential to treat COVID-19. We hope that our article can provide a theoretical basis for later experiments.     

Early risk factors of the exacerbation of coronavirus disease 2019 pneumonia

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest computed tomography (CT). All laboratory examinations were measured within first 24 hours after admission, and chest CT was performed before admission. A total of 56 (65.9%) patients had a history of exposure to the Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (P = .003) and coronary heart disease (P = .017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (P < .001). Severe and critical patients showed higher white blood cell count (P = .006), neutrophil (NEU) count (P = .001), NEU% (P = .002), procalcitonin (P = .011), C-reactive protein (P = .003), prothrombin time (P = .035), D-dimer (P = .025), aspartate aminotransferase (P = .006), and lower lymphocyte (LYM) count (P = .019), LYM% (P = .001), albumin (P < .001). Logistic regression analysis showed that NEU count is an independent risk factor for deterioration, with the threshold of 6.5 × 10⁹·L⁻¹. We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease.     

Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019

ObjectiveTo determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19).MethodsFrom January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored.ResultsClearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.ConclusionsSARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.     

多排螺旋CT联合多平面重建技术在新型冠状病毒肺炎诊断中的应用

目的探讨多排螺旋CT联合多平面重组技术(MPR)在新型冠状病毒肺炎(COVID-19)早期筛查诊断中的应用价值。方法回顾性分析2020年1~2月我院发热门诊32例疑似COVID-19患者的影像资料,对比原始CT轴位图像和重建后高分辨CT(HRCT)轴位图像结合MPR重组技术对COVID-19影像特征的检出能力,并用SPSS 17.0软件对病灶检出率进行χ2检验分析。结果重建后的HRCT轴位图像可以清楚显示肺小叶内部结构变化,尤其是结合MPR重组技术后在显示跨叶段病灶、支气管充气征、血管束增粗征等病变上优于原始CT轴位图像,差异具有统计学意义(P<0.05)。结论COVID-19疫情爆发期,尽早使用多排螺旋CT扫描,重建HRCT轴位图像并联合运用MPR技术,能够更加直观、立体地显示病灶,为COVID-19的快速鉴别诊断提供更丰富的影像依据,从而早隔离、早治疗,控制疫情发展。