Genetic Variation of the ORF5 Gene of Porcine Reproductive and Respiratory Syndrome Virus in East China during 2008-2010

[Objective] A total of 260 swine samples of dead or sick pigs collected from 7 provinces （municipalities） Jiangsu, Anhui, Shanghai, Shandong, Zhejiang, Fujian and Jiangxi of China during 2008-2010 were detected for porcine reproductive and respiratory syndrome virus （PRRSV）. And the ORF5 genes of some isolates were amplified and sequenced for understanding the molecule epidemiology and the genetic evolution of PRRSV in East China. [Method] Using RT-PCR method, PRRSV was detected by RT-PCR from samples. The complete ORF5 genes of 36 PRRSV positive samples was amplified, sequenced and analyzed with other 15 strains available on GenBank. [Result] PRRSV was detected in 118/260 of the clinical samples, with a positive rate was 45.4%. Sequence analysis showed that the 36 isolates of this study belonged to the North American-type PRRSV strains and were closely related to the highly pathogenic PRRSV （HP-PRRSV） with 94.6%-100% amino acid sequence identities. The sequence analysis combined with the phylogenetic analysis indicated that all these North American-type PRRSV strains in East China were further divided into five subgenotypes, subgenotype Ⅲ showed closer identity with HPPRRSV; almost all subgenotypes were found to be variable in the primary neutralizing epitope; subgenotypes Ⅲ and IV had more glycosylation sites than others. Although these 36 isolates were collected from different provinces in East China, there were no obvious relations between the distribution of PRRSV and the region. [Conclusion] The PRRSV infection was widespread and HP-PRRSV was the popular strain in East China during 2008-2010. However some different genetic characteristics appeared in the genomes, the genetic evolution was relatively stable. There exists a cross-cutting phenomenon on the genetic relationship of PRRSV isolates obtained from different provinces. Subgenotypes IV and V only appeared in some provinces, but the distribution of PRRSV did not show apparent geographical characteristics.

Serological Study of An Imported Case of Middle East Respiratory Syndrome and His Close Contacts in China, 2015

The first imported Middle East respiratory syndrome （MERS） case in China was identified in May 2015. We determined the kinetics of antibody （IgG and IgM） and neutralizing antibodies against MERS-coronavirus （MERS-CoV） in this case before discharge. Moreover, no seroconversion was found among 53 close contacts by anti-MERS IgG antibody enzyme-linked immunosorbent assay （ELISA） of paired serum samples. These findings suggest that neither community nor nosocomial transmission of MERS-CoV occurred in China.

Life after recovery from SARS,influenza,and Middle East respiratory syndrome: An insight into possible long-term consequences of COVID-19

Viral infectious diseases have become an increased public health issue in the past 20 years.The outbreaks of severe acute respiratory syndrome coronavirus(SARSCoV-1)in 2002,influenza H1N1 in 2009,Middle East respiratory syndrome-CoV in 2012,and the current new coronavirus SARS-CoV-2 have shown that viral infectious diseases are a major concern in the 21st century.As the world lives under the pandemic of a new coronavirus(COVID-19),knowing the clinical characteristics from those past diseases and their long-term outcomes is important to understand the current coronavirus pandemic and its complications and consequences better and plan for possible future outbreaks.Several long-term complications have been described with these respiratory viral diseases,such as decreased pulmonary function,pulmonary fibrosis,chronic fatigue syndrome,avascular necrosis of bone,polyneuropathy,encephalitis,posttraumatic stress disorder,depression,and anxiety.This article summarizes several studies describing chronic complications and long-term outcomes of patients recovered from these viral syndromes.

Sero-prevalence of Middle East Respiratory Syndrome Coronavirus among Camels at a Slaughterhouse in Kenya, 2015

Dromedary camels are implicated as reservoirs of MERS-CoV （Middle East Respiratory Syndrome coronavirus）. High prevalence of MERS-CoV antibodies in dromedaries in Africa and Arabian Peninsula was demonstrated from sera archived between 1992 and 2012 with matching of camel-derived and human-derived sequences from various regions suggesting zoonotic transmission. We assessed sero-prevalence of anti-MERS-CoV antibodies among dromedaries at Athi-River slaughterhouse, Kenya. Proportions were calculated and associations between anti-MERS-CoV antibody sero-positivity and age group, sex, and origin of camels were assessed using Chi-square tests. Out of 373 specimens, 53% were females, antibody sero-prevalence was 82%. Sero-prevalence did not differ by age group, sex, or origin. This study reports high sero-prevalence of MERS-CoV antibodies demonstrated among camels brought for slaughter from different regions of Kenya. This was consistent with other studies in Africa among adult camels and further proves that the virus likely remains present in Kenya. Since only mature camels were assessed, more studies on younger populations of camels could help determine the dynamics of virus transmission. Though the risk from mature animals is not known, at some point these camels become re-infected and human populations exposed to camels may still face some risks.

Mental health impact of the Middle East respiratory syndrome,SARS,and COVID-19:A comparative systematic review and metaanalysis

BACKGROUND Over the last few decades,3 pathogenic pandemics have impacted the global population;severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV)and SARS-CoV-2.The global disease burden has attributed to millions of deaths and morbidities,with the majority being attributed to SARS-CoV-2.As such,the evaluation of the mental health(MH)impact across healthcare professionals(HCPs),patients and the general public would be an important facet to evaluate to better understand short,medium and long-term exposures.AIM To identify and report:(1)MH conditions commonly observed across all 3 pandemics;(2)Impact of MH outcomes across HCPs,patients and the general public associated with all 3 pandemics;and(3)The prevalence of the MH impact and clinical epidemiological significance.METHODS A systematic methodology was developed and published on PROSPERO(CRD42021228697).The databases PubMed,EMBASE,ScienceDirect and the Cochrane Central Register of Controlled Trials were used as part of the data extraction process,and publications from January 1,1990 to August 1,2021 were searched.MeSH terms and keywords used included Mood disorders,PTSD,Anxiety,Depression,Psychological stress,Psychosis,Bipolar,Mental Health,Unipolar,Self-harm,BAME,Psychiatry disorders and Psychological distress.The terms were expanded with a‘snowballing’method.Cox-regression and the Monte-Carlo simulation method was used in addition to I2 and Egger’s tests to determine heterogeneity and publication bias.RESULTS In comparison to MERS and SARS-CoV,it is evident SAR-CoV-2 has an ongoing MH impact,with emphasis on depression,anxiety and post-traumatic stress disorder.CONCLUSION It was evident MH studies during MERS and SARS-CoV was limited in comparison to SARS-CoV-2,with much emphasis on reporting symptoms of depression,anxiety,stress and sleep disturbances.The lack of comprehensive studies conducted during previous pandemics have introduced limitations to the“know-how”for clinicians and researchers to better support patients and deliver care with limited healthcare resources.

A Rare Classical Presentation of Bardet-Biedl Syndrome in a Three-Year-Old Male from South East Nigeria: A Case Report

Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by obesity, post-axial polydactyly, renal abnormalities, mental retardation, pigmentary retinopathy and hypogenitalism. Diagnosis is rare in early childhood, and only few of the features are present at that age. This is because the disease is slow evolving. However, it is possible to find majority of the component of this syndrome in very young children. A 3-year old very obese male presented with clinical features of sepsis and congestive cardiac failure. He is a product of non-consanguineous marriage with unremarkable family history. Both parents are of the Ibo tribe in Nigeria. Polydactyly was noticed at birth. There was delay in some aspects of his developmental milestone. Examination revealed mild hypertelorism and retrognathia, polydactyly of both feet with syndactyly of the big and second toes. Other findings were short broad hands, mottled pigments on the retina, moderate mental retardation, hypogenitalism, nephrotic syndrome, renal tubulopathy, hyperglycaemia and hypopigmented skin lesions. A case of BBS with all the primary features and some secondary manifestations in a very young child is hereby reported. A high index of suspicion for BBS should be shown in any young child with at least one of the features of this syndrome. This will enhance earlier diagnosis and improve disease outcome.

EAST/SeSAME综合征患儿1例的临床特征及遗传学分析

目的探讨1例表现为癫痫、感音神经性耳聋、共济失调、智力障碍的男性EAST/SeSAME患儿的遗传学病因。方法选取2021年1月至郑州大学第三附属医院就诊的1例EAST/SeSAME综合征患儿为研究对象。对患儿及其父母进行高通量测序检测,对候选变异进行Sanger测序验证及生物信息学分析。结果测序结果显示患儿KCNJ10基因存在c.557T>C(p.Val186Ala)和c.386T>A(p.Ile129Asn)复合杂合变异,Sanger测序证实二者分别遗传自其母亲和父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南,二者均判定为可能致病性变异(PM1+PM2_Supporting+PP3+PP4;PM1+PM2_Supporting+PM3+PP3+PP4)。结论患者为KCNJ10基因复合杂合变异所致的EAST/SeSAME综合征。上述发现丰富了KCNJ10基因的变异谱,并为患儿家庭的遗传咨询及产前诊断提供了依据。

EAST/SeSAME耳聋综合征及内向整流性钾离子通道Kir4.1在内耳中的功能表达

EAST或者SeSAME耳聋综合征是一种新发现的常染色体隐形遗传病,由KCNJ10基因突变产生。KCNJ10基因编码内向整流性钾离子通道4.1（inwardly rectifying potassium channel 4.1,Kir4.1）的特点是在细胞膜电位超极化情况下电导增加,而去极化情况下电导降低,

免疫信息学方法预测针对中东呼吸综合征冠状病毒的T/B细胞抗原表位

目的通过免疫信息学方法预测针对中东呼吸综合征冠状病毒(MERS-CoV)的T/B细胞抗原表位。方法从NCBI获取S蛋白序列后,运用MEGA11进行多序列比对及系统发育树构建,Expasy Protparam分析其理化性质,SOPMA预测其二级结构。随后对S蛋白建模并进行模型验证。再通过NetCTL-1.2、NetMHC pan EL 4.1和IEDB预测杀伤性T细胞(CTL)表位,NetMHCⅡpan-4.0、IFNepitope和IL-4pred预测辅助性T细胞表位(HTL),ABCpred和BepiPred-2.0预测线性B细胞表位(LBL),ElliPro工具预测构象B细胞表位(CBL)。最后对上述预测得到的线性表位进行抗原性、致敏性和毒性预测。结果S蛋白序列保守性较高,且来自不同国家的100个MERS-CoV S蛋白可以装进同一系统进化枝。理化性质分析结果显示,S蛋白亲水性总平均值为-0.078,在哺乳动物网织红细胞中半衰期约为30 h。模型验证结果显示构建的S蛋白模型是合理的。从S蛋白中预测得到具有抗原性、无致敏性和无毒性的CTL表位2个、HTL表位2个,LBL表位15个。ElliPro工具预测得到的CBL表位5个。结论MERS-CoV的S蛋白是亲水性的稳定蛋白;综合多种生物信息学方法可以预测得到T/B细胞抗原表位,对开发针对MERS-CoV的多肽疫苗具有重要借鉴意义。

Population-based carrier screening and prenatal diagnosis of fragile X syndrome in East Asian populations

Identification of carriers of fragile X syndrome(FXS) with the subsequent prenatal diagnosis and knowledge of FXS-associated genetic profiles are essential for intervention in specific populations. We report the results of carrier screening of 39,458 East Asian adult women and prenatal diagnosis from 87 FXS carriers.The prevalence of FXS carriers and full mutation fetuses was estimated to be 1/581 and 1/3124 in East Asian populations, respectively. We confirmed the validity of the current threshold of CGG trinucleotide repeats for FMR1 categorization;the integral risks of full mutation expansion were approximately 6.0%,43.8%, and 100% for premutation alleles with 55—74, 75—89, and ≥ 90 CGG repeats, respectively. The protective effect of AGG(adenine-guanine-guanine nucleotides) interruption in East Asian populations was validated, which is important in protecting premutation alleles with 75—89 CGG repeats from full mutation expansion. Finally, family history was shown not an effective indicator for FXS carrier screening in East Asian populations, and population-based screening was more cost-effective. This study provides an insight into the largest carrier screening and prenatal diagnosis for FXS in East Asian populations to date. The FXSassociated genetic profiles of East Asian populations are delineated, and population-based carrier screening is shown to be promising for FXS intervention.

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%—60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 ×10^9/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32 38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

Genetic Evidence of Middle East Respiratory Syndrome Coronavirus(MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels(82.37%, 95%confidence interval(CI) 79.50–84.91). More female camels were significantly seropositive(74.28%, 95% CI 71.14–77.19)than male camels(P \ 0.001)(53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERSCoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4 b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.

Middle East respiratory syndrome coronavirus： current situation and travel-associated concerns

The emergence of Middle East respiratory syndrome coronavirus （MERS-CoV） in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus （SARS-CoV） in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate （CFR） of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.

Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020

Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases<65 years but with a lower risk(adjusted OR=0.31,95%Cl:0.18-0.51)among male cases>65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

Diabetes Risk Factor and Its Relationship to Increasing Coronavirus (COVID-19) Mortality Rate in United States in 2019-2022: An Epidemiological Study

As an effort to understand the effect of diabetes on the increasing rate of COVID-19 infection, we embarked upon a detailed statistical analysis of various datasets that include COVID-19 infection and mortality rate, diabetes and diseases that may contribute to the severity and risk factor of diabetes in individuals and this impact on COVID-19 and the mortality rate. These diseases include respiratory diseases, cardiovascular diseases, and obesity. Equally significant is the statistical analysis on ethnicity, age, and sex on COVID-19 infection as well as mortality rate. Their possible contributions to increasing the severity and risk factor of diabetes as a risk to mortality to individuals who have COVID-19. Objectives: The ultimate objectives of this investigation are as follow: 1) Is there a risk factor of diabetes on COVID-19 infection and increasing mortality rate? 2) To what extent do other disease conditions that include, obesity, heart failure, and respiratory diseases influence the severity and risk factor of diabetes on increasing COVID-19 infection and mortality rate? 3) To what extent does age, race, and gender increase the mortality of COVID-19 and increase the severity and risk factor of diabetes on COVID-19 mortality rate? 4) How and why COVID-19 virus increases the risk of diabetes in children? 5) Diabetes and COVID-19: Who is most at Risk? Lastly, understanding the misconception of COVID-19 and diabetes.

刘红权主任基于风从东方来辨治颈椎病经验浅析

“风从东方来”理论最早出现在《灵枢·九宫八风第七十七》。刘红权老师应用该理论辨证论治颈椎病,提到需深入理解中医经典著作,合理将九宫八风、藏象学说以及天人相应理论相互结合起来,在内注重疏肝养脾、疏经通络,在外可恰当融合人类与天地中四季节气变化,疾病有理可循,诊治有据可依,人类运动变化最终才能生生不息朝着稳定方向前进。

Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin

The papain-like protease(PL^(pro)) of Middle-East respiratory syndrome coronavirus(MERS-CoV) has proteolytic,deubiquitinating,and de ISGylating activities.The latter two are involved in the suppression of the antiviral innate immune response of the host cell.To contribute to an understanding of this process,we present here the X-ray crystal structure of a complex between MERS-CoV PL^(pro) and human ubiquitin(Ub) that is devoid of any covalent linkage between the two proteins.Five regions of the PL^(pro) bind to two areas of the Ub.The C-terminal five residues of Ub,RLRGG,are similar to the P5–P1 residues of the polyprotein substrates of the PL^(pro) and are responsible for the major part of the interaction between the two macromolecules.Through sitedirected mutagenesis,we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL^(pro).The enzyme appears not to be optimized for catalytic efficiency; thus,replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities.Ubiquitin binding by MERS-CoV PL^(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL^(pro).The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL^(pro).

Lucky China： Efficient Prevention from Middle East Respiratory Syndrome and its Beyond

Middle East respiratory syndrome （MERS） has recently drawn worldwide attention since its nosocomial or suspected community-acquired clusters in South Korea, which has been the largest and the most complex outbreak of the Middle East Region since 2012. It is such a large fortune for China to be able to prevent effectively from MERS, not only by actively monitoring the Korean imported case based on the notification of WHO Western Pacific Region Office （WPRO）, but also by properly quarantining a number of close contacts. Otherwise, China might undergo the same situation as in South Korea, or even worse, if the patient kept on traveling through Southern China or went to health care facilities without wearing any personal preventing equipment. To date, this laboratory-confirmed MERS patient has recovered and been discharged from hospital, and none of the close contacts （n = 75） has showed any associated symptoms, so lucky for him and China.

Middle East respiratory syndrome:what to be concerned more in preparedness?

The recent problem on Middle East respiratory syndrome is a very interesting new infection emerging from the Gulf area. For practitioners in intensive care medicine, knowledge update on this new emerging infection is needed. Preparation for diagnostic tool and antiviral drug to cope with possible outbreak is suggested. In addition, the consideration of ecological factors of this new disease is important. The consideration of not only ecological but also humanistic background can be useful to manage the new disease, Middle East respiratory syndrome as well. Finally, how to improve medical service for underserved population is a big issue. The local health department must play an important role.

Stochastic and spatio-temporal analysis of the Middle East Respiratory Syndrome outbreak in South Korea, 2015

South Korea was free of the Middle East Respiratory Syndrome(MERS)until 2015.The MERS outbreak in South Korea during 2015 was the largest outbreak of the Coronavirus outside the Middle East.The major characteristic of this outbreak is inter-or intra-hospital transmission.This recent MERS outbreak in South Korea is examined and assessed in this paper.The main objectives of the study is to characterize the pattern of the MERS outbreak in South Korea based on a basic reproductive ratio,the probability of ultimate extinction of the disease,and the spatio-temporal proximity of occurrence between patients.The survival function method and stochastic branching process model are adapted to calculate the basic reproductive ratio and the probability of ultimate extinction of the disease.We further investigate the occurrence pattern of the outbreak using a spatio-temporal autocorrelation function.