Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 -S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

BACKGROUNDCoronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODSAn integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n = 484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n = 564) at both nucleotide and protein levels. RESULTSPhospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. Up to 100% positive rates of PLA2G7 were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non-COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was significantly lower than that in moderate pneumonia (P = 7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P = 0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONSWe firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response. FUNDINGThis study was supported by grants from China Mega-Projects for Infectious Disease (2018ZX10711001), National Natural Science Foundation of China (82041023).

Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. MethodBetween January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. FindingsNotably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. InterpretationOur findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. FundingNational Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Author summaryIn this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.

Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

Multiple approaches for massively parallel sequencing of HCoV-19 genomes directly from clinical samples

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

Correlation of serum homocysteine levels with hematoma absorption and cognitive function in elderly patients with cerebral hemorrhage / 中华老年医学杂志

Objective:To analyze the correlation of serum homocysteine(Hcy)levels with hematoma absorption and cognitive function in elderly patients with cerebral hemorrhage.Methods:Clinical data of 80 elderly patients with cerebral hemorrhage admitted to our hospital from January 2017 to July 2019 were retrospectively analyzed.According to serum levels of Hcy(normal range: <15 μmol/L), 21 patients with serum Hcy<15 μmol/L were included in Group A, and 59 patients with Hcy≥15 μmol/L were included in Group B. General data(gender, age, hypertension, diabetes, bleeding part, bleeding volume, etc.), hematoma absorption and cognitive function were recorded and compared between the two groups.The correlation of serum Hcy levels with hematoma absorption and cognitive function in elderly patients with cerebral hemorrhage was analyzed by using Spearman correlation analysis.Results:There was no statistical difference in gender, age, hypertension, diabetes, bleeding location and bleeding volume between the two groups.The speed of hematoma absorption and scores of Montreal Cognitive Assessment(MoCA)were higher in Group A than in Group B[(0.4±0.1)ml/d vs.(0.3±0.1)ml/d, (19.6±4.6)points vs.(16.3±3.3)points, t=3.935 and 3.532, both P=0.000]. Spearman correlation analysis showed that serum Hcy level was negatively correlated with hematoma absorption and cognitive function in elderly patients with cerebral hemorrhage( r=-0.372 and-0.311, P=0.000 and 0.005), indicating that hematoma absorption and cognitive function were worse with the higher serum Hcy levels in elderly patients with cerebral hemorrhage. Conclusions:Serum Hcy levels change in elderly patients with cerebral hemorrhage.As serum Hcy levels increase, the risk for adverse events such as slow hematoma absorption and unsatisfactory improvement in cognitive function in patients increases accordingly.Serum Hcy levels play an important role in the occurrence and development of diseases in elderly patients with cerebral hemorrhage and can be used to evaluate the condition and prognosis of patients with cerebral hemorrhage.

Development of a triplex real-time RT-PCR assay to detect Zika, Chikungunya and Mayaro viruses / 中华实验和临床病毒学杂志

Objective@#To establish a method for the simultaneous identification of Zika, Chikungunya and Mayaro viruses.@*Methods@#The complete genome sequences of Zika, Chikungunya and Mayaro virus were retrieved from Global Shared Database for comparative analysis, estimate its conservative region and determine the target gene location, specific primers and probes were designed, then a triplex real-time RT-PCR assay was developed. The specificity, sensitivity and repeatability of the assay were assessed by viral nucleic acid of Zika virus, Chikungunya virus a, in vitro transcriptional RNA of Mayaro virus, normal human serum and related virus simulation sample.@*Results@#The result showed that the established method could detect Zika virus, Chikungunya virus, as well as simulated Mayaro virus samples, the limit of detection (LOD) of Zika and Chikungunya virus was 16.22 Copy/PCR and 12.02 Copy/PCR, respectively, the LOD for simulated Mayaro virus RNA was 2.82 Copy/PCR, no significant difference was detected between the triplex and monoplex assays. No cross reaction was found in the detection of dengue virus, Hantavirus, severe fever with thrombocytopenia syndrome (SFTS) virus, yellow fever virus and influenza virus, and 100 healthy adults blood samples, the specificity of the method was 100%. The repeatability result showed that the standard deviation of all three detections were blow 0.5 and the coefficient of variation was less than 2% by selecting viral nucleic acids or transcribed RNA with high, medium and low concentration gradients.@*Conclusions@#A triplex real-time RT-PCR assay for detection of Zika, Chikungunya and Mayaro virus has been established with an acceptable specificity, sensitivity and repeatability.

Development of a luminex-based multiplexed immunoassay for detection of IgG antibodies to the viral hemorrhagic fever epidemic in Africa / 中华实验和临床病毒学杂志

Objective@#To establish a multiplexed immunoassay for detection of IgG antibodies against viral hemorrhagic fever epidemic in Africa.@*Methods@#The recombinant antigens of hemorrhagic fever viruses (HFVs) epidemic in Africa were expressed and purified, and then coupled with the fluorescent microspheres. The coupling effects were evaluated by monoplexed detection of rabbit immune sera. Blood specimens were collected from people from Africa with fever, and multiplexed detection of IgG antibodies to HFVs was performed. Comparison of multiplexed assay and ELISA was performed by paired χ2 test using SPSS software.@*Results@#Both the purity and concentration of HFVs recombinant antigen met the standards for coupling and detection, and the antigens were successfully coupled with fluorescent microspheres. Seventy-eight sera samples of people from Africa with fever were multiplex detected. Among these, one was tested positive for LASV-specific IgG, one was tested positive for LUJV-specific IgG, 4 were tested positive for DENV-specific IgG and 6 tested positive for YFV-specific IgG. There was no statistically significant difference compared with ELISA, and the two method were highly correlated.@*Conclusions@#A multiplexed luminex-based immunoassay for detection of IgG antibodies to viral hemorrhagic fever epidemic in Africa was established, which laid the foundation for the differential diagnosis.

A fluorescent bead-based multiplex PCR assay for the simultaneous detection of seven viral diseases endemic in Africa / 中华实验和临床病毒学杂志

Objective@#To establish a fluorescent bead-based multiplex assay for the simultaneous detection of seven viral diseases endemic in Africa.@*Methods@#The genomic sequences of the viral pathogens causing Rift valley fever, Yellow fever, Marburg virus disease, Ebola virus disease, Lassa fever, Crimean-Congo hemorrhagic fever and Chikungunya fever were compared, PCR detection target fragments were selected, and amplification primers and hybrid probes were designed. The reference samples of related pathogens were prepared by chemical synthesis of DNA and in vitro transcription RNA. The sensitivity and stability of the detection method were evaluated. The specificity was evaluated by testing 30 samples of suspected dengue fever, and hantavirus diseases, and 32 healthy human blood samples.@*Results@#The fluorescent bead-based multiplex assay could specifically detect the corresponding pathogen, the detection limit was at a range of 102-105 copies/ μl, the specificity was 100%, and the intra-assay coefficient of variation was below 12%, and the inter-assay coefficient of variation was below 15%.@*Conclusions@#A fluorescent bead-based multiplex PCR assay for the simultaneous detection of seven viral diseases endemic in Africa was established, which may provide a new choice for the screening of suspected infectious diseases.

Development of a double antibody sandwich ELISA for detection of Chikungunya virus antigen / 中华实验和临床病毒学杂志

Objective@#To establish a method for detection of chikungunya virus(CHIKV) antigen.@*Methods@#CHIKV virus like particle(VLP), that contains all structural proteins, was prepared by baculovirus expression system. Mice and rabbits were immunized with the VLP to develop antibodies against CHIKV. A double antibody sandwich ELISA was established for detection of CHIKV antigens. The concentrations of the antibodies used and the reaction conditions were optimized. The detection limit and repeatability of the ELISA was evaluated.@*Results@#The sensitivity and specificity was estimated by 10 mimicking CHIKV sera, 90 health person sera, 40 other virus infected sera. It was show that the specificity of DAS-ELISA was 100%, the detection limit was 10 TCID50, the coefficients of variation (CV) within plate was <5%, the CV of different plates was <10%.@*Conclusions@#The double antibody sandwich ELISA established in this study can be used to detect the CHIKV antigen in acute phase serum of patient and provide a method for detection of CHIKV.

Effect of preoperative stellate ganglion block on gastrointestinal function in rats undergoing abdominal surgery / 临床麻醉学杂志

Objective To observe the effect of preoperative stellate ganglion block (SGB)on gastrointestinal function in rats undergoing gastrointestinal and non-gastrointestinal abdominal surgery.Methods Fifty-four male SD rats,weighing (200 ± 10 )g,were randomly divided into 5 groups:control group (n =6,group C),gastrointesinal abdominal surgery group (n =12,group G), SGB+gastrointesinal abdominal surgery group (n = 12,group SG),non-gastrointestinal abdominal surgery group (n = 12,group NG),SGB+ non-gastrointestinal abdominal surgery group (n = 12, group SNG).Group C was given no treatment.Venous blood samples were taken for determination of the levels of serum NE,TNF-αand IL-6 at the time before stellate ganglion block (T1 ),the end of operation (T2 ),12 h (T3 )and 24 h after operation (T4 ).Six rats were randomly chosen from each group to test bowel propulsion rate at T3 and T4 ,then sacrificed to measure motilin (MTL)and vaso-active intestinal peptide (VIP)in antrum and proximal colon.Results Compared with T1 and group C,the serum concentrations of NE,TNF-αand IL-6 significantly increased at T2-T4 in groups G,SG, NG and SNG (P <0.05).The NE,TNF-α and IL-6 levels in group G were significantly higher than those in group SG (P <0.05),and the serum NE,TNF-αand IL-6 levels in group NG were signifi-cantly higher than those in group SNG (P <0.05).Compared with T3 and group C,the bowel pro-pulsion rate and MTL levels significantly increased at T4 in groups G,SG,NG and SNG (P <0.05). The bowel propulsion rate and MTL levels in group SG and group SNG were significantly higher than those in group G and group NG,respectively (P <0.05 ).The VIP levels significantly decreased in groups G,SG,NG and SNG than that in group C (P <0.05).The VIP levels in group SG were sig-nificantly lower than those in group G (P < 0.05 ), and the VIP levels in group SNG were significantly lower than those in group NG (P < 0.05 ).Conclusion Preoperative stellate ganglion block can premote the recovery of gastrointestinal function in rats after abdominal surgery,attenuated stress response and inflammatory reaction,and regulation of gastrointestinal hormone level may be involved in the mechanism.

The Early Prognostic Value of Serum Sodium Level in Patients With Acute ST-elevation Myocardial Infarction / 中国循环杂志

Objective: To explore the relationship between serum sodium level and early prognosis in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 7461 STEMI patients within 12h of onset who matched the diagnostic standard of European society of cardiology and American college of cardiology were retrospectively studied. According to serum sodium levels within 24h of admission, the patients were categorized into 3 groups: Serum sodium≥135 mmol/L group, Serum sodium 130-134 mmol/L group and Serum sodium<130 mmol/L group. The baseline condition, 30-day mortality with other adverse events and the effect of neuroendocriology inhibitor treatment were compared among 3 groups; their relationships to serum sodium level were analyzed. Results: Serum sodium<130 mmol/L group had the higher 7-day and 30-day mortality than the other 2 groups, both P<0.001; compared with Serum sodium≥135 mmol/L group, Serum sodium<130 mmol/L group presented the higher occurrence rates of 30-day cardiac shock, heart failure (HF) and life-threatening arrhythmia, P<0.001. With adjusted affecting factors of age, diuretic and reperfusion treatments, serum sodium<130 mmol/L was still related to 7-day and 30-day mortality (OR=1.69 and OR=1.57). Both single and multivariable analysis indicated that serum sodium<130 mmol/L was related to cardiac shock (OR=1.75 and OR=1.64), HF (OR=1.42 and OR=1.30) and life-threatening arrhythmia (OR=1.53 and OR=1.34). In all 3 groups, the patients using ACE inhibitor, β-blocker or both medications had reduced 30-day mortality than those without such medication, allP<0.001; the reduction was more obvious in Serum sodium<130 mmol/L group than the other 2 groups,P<0.001. Conclusion: Serum sodium level<130 mmol/L within 24h of admission was the risk factor for the early stage main adverse events as mortality, cardiac shock, HF and life-threatening arrhythmia in acute STEMI patients.

Prevalence of obstructive sleep apnea-hypopnea syndrome in adults aged over 60 yeaes in dongying city / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To survey the prevalence of obstructive sleep apnea-hypopnea syndrome(OSAHS) in adults aged over 60 years in Dongying city,and analyze the risk factors and the extent of damage to the quality of life for the elderly to provide the basis for prevention and treatment of OSAHS people.@*METHOD@#One thousand subjects were derived from a random cluster sampling in seven districts of Dongying city:they were asked to answer the questions from questionnaires. According to the questionnaire scoring, 100 subjects in high-risk group were selected randomly to make polysomnography monitoring for a whole night,so that the prevalence of the disease was calculated and the related risk factors were analyzed; elderly patients diagnosed with OSAHS were asked to assess the quality of life assessment questionnaire by face to face to understand the quality of life dimensions injury.@*RESULT@#The actual number of completed surveys was 934, and the efficiency was 93.4%. The estimated prevalence of OSARS in elder people defined by apnea-hypopnea index (AHI ≥ 5) was 32.5%; Multivariate analysis revealed that age smoking, family snoring,neck circumference, waist circumference, and abnormality of the upper airway were respectively independent risk factors of OSAHS,and the abnormalities of the upper airway had the most obvious impact on AHI. The damage caused by OSAHS to the quality of life for elderly people followed their daily work life, social relationships, symptoms, alertness, emotional, general health, symptoms.@*CONCLUSION@#The estimated prevalences of OSAHS in elder people were high. Actively promoting good habits to older people, weight loss, early detection and correct upper airway abnormalities may reduce the estimated prevalence of OSAHS. In the treatment process, the patient's physician should pay attention to their emotional and groom their psychological problems to improve the quality of life in elder people.

Epidemiological characteristics of Zika virus disease / 中华流行病学杂志

Zika virus disease is an emerging mosquito-borne acute infectious disease caused by Zika virus,so far there have been no available vaccine or specific treatment.Currently,the outbreaks of Zika virus disease mainly occurs in the Americas,but the regional distribution of the disease is in rapid expansion,34 countries and territories have reported autochthonous transmission of the virus.The illness is usually mild with very rarely death,but increased reports of birth defects and neurologic disorders in the areas affected by Zika virus has caused extensive concern worldwide.In China,the competent vectors for Zika virus are widely distributed,imported viraemic cases may become a source of local transmission of the virus.However,Zika virus disease is preventable,the spread of virus could be stopped when the effective prevention measures are taken.This paper summarizes the retrieval results from Medline database and the information from the reports of the governments of countries affected or health organizations about the epidemiological characteristics of Zika virus disease.

Effect of interaction between ADIPOQ gene 11377C/G polymorphism and physical activity on metabolic syndrome in children / 实用医学杂志

Objectve To study the effect of interaction between ADIPOQ 11377C/G (rs266729) gene polymorphism and physical activity in metabolic syndrome in children. Methods We conducted a case-control study in 114 cases and 114 controls. The genotype of ADIPOQ 11377C/G had been detected in direct sequenc-ing. The effect of interaction between gene polymorphism and physical activity was evaluated by a crossover analysis. Results Efficient physical activity was a protective factor (OR = 0.14); there was interaction between inefficient physical activity and CC genotype of 11377C/G which was a risk factor for metabolic syndrome in children. Conclusion Efficient physical activity can reduce the risk of metabolic syndrome in children. There was interaction between 11377C/G (rs266729) polymorphism and physical activity.

Expression, purification of recombinant human cryptochrome I and its application in preparation of protective agent for radiotherapy / 生物工程学报

Radiotherapy is a treatment for cancer with undesired by-effects. In order to develop a new radiation protective agent that could reduce the by-effects, we tried to express and purify human cryptochrome 1 (hCRY1). The coding sequence of hCRY1 was inserted into prokaryotic expression plasmid pET28a(+), and this protein was purified from Escherichia coli BL21(DE3) after IPTG induction, ultrasonication, inclusion body dissolution, gradient dialysis, nickel column purification and ultrafiltration. The yield of hCRY1 in 1 L E. coli culture (LB medium) was about 10-15 mg. The radiation protective efficiency of hCRY1 was monitored by detecting X-ray-induced H2A.X foci in HaCaT cells. The results of immunofluorescence show that hCRY1 significantly reduces X-ray stimulated DNA damage response. The apoptosis of HaCaT cell was also detected, and the repression of H2A.X foci formation was not due to hCRY1's cytotoxity. All these data suggest a potential application of recombinant hCRY1 as a protective agent for radiotherapy.

Diagnosis and treatment of facial nerve hemangioma / 中国耳鼻咽喉头颈外科

[ABSTRACT]OBJECTIVETo study clinical features and imaging manifestations of facial nerve hemangioma. METHODSClinical data of 5 cases with facial nerve hemangioma, who were diagnosed and treated in facial lab of Beijing Shijitan hospital between January 2006 and December 2011, were collected. There were 2 male and 3 female. The age ranged from 29-44 years. Among the 5 cases with facial nerve hemangioma, both HRCT of temporal bone and facial nerve enhancement MRI were performed on 4 cases, and one case underwent facial nerve enhancement MRI examination only.RESULTSAll the 5 cases firstly presented with sudden unilateral facial palsy. Facial palsy affected the left and right side in 4 cases and 1 case, respectively. Geniculate ganglion was affected in all cases. Local bony canal expansion at geniculate ganglion, labyrinthine segment and horizontal segment was the main manifestation of facial nerve hemangioma on HRCT, and the surrounding bone was incontinuous and less regular. The typical appearance was point-shape or pin-shape, similar to honeycomb structure. On MRI, soft tissue node image around geniculate ganglion accompanied by thickness of the adjacent facial nerve was the chief appearance. It showed mixed T1, uneven and slightly longer T2 signal with less clear border on horizontal scanning, and abnormal enhancement was exhibited after enhancement scanning.CONCLUSIONDetailed history together with HRCT of temporal bone and multi-planar reconstruction MPR as well as facial nerve enhancement MRI were useful for preoperative diagnosis of facial nerve hemangioma. The tumor should be removed with surgical approach was based on hearing conditions, tumor scale and the affected sites.in order to preserve integrity of facial nerve if possible.

Relationship Between Platelet Counts at Admission and In-hospital Mortality in Patients With Type A Acute Aortic Dissection / 中国循环杂志

Objective: To explore the relationship between platelet counts at admission and in-hospital mortality in patients with type A acute aortic dissection (AAD). Methods: We investigated 183 consecutive patients with CT conifrmed diagnosis of type A AAD treated in our hospital from 2012-02 to 2013-05. There were 126 (68.9%) male and the patients were divided into 3 sets of groups.①In-hospital surviving group,n=157 and In-hospital death group,n=26.②According to platelet counts, the patients were divided into 5 groups: Q1 group, platelet counts ≤ 119×109/L,n=36, Q2 group, platelet (120-149) ×109/L,n=37, Q3 group, platelet (150-173)×109/L, n=36, Q4 group, platelet (174-228)×109/L,n=37, Q5 group, platelet >228×109/L,n=37.③At admission, platelet ≤ 119×109/L,n=36 and platelet >119×109/L,n=147. In addition, the patients were further divided into another 4 groups based on operative condition: platelet ≤ 119×109/L with operation,n=18, without operation,n=18; platelet > 119×109/L with operation,n=96, without operation,n=51. The basic information at admission including platelet counts, WBC and D-dimer were studied in all groups, the primary endpoint was in-hospital mortality. Results: The overall in-hospital mortality was 14.3%. Compared with In-hospital surviving group, the In-hospital mortality group had decreased platelet counts, lower blood pressure and higher level of D-dimer. The mortality in Q1 group (38.9%) was higher than those in Q2, Q3, Q4 and Q5 groups (10.8%, 11.1%, 8.1% and 2.7%), allP<0.001. The risk of death in Q5 group was higher than Q1 group (HR=11.2, 95% CI 2.13-123.3,P=0.007). With adjusted age, gender and other relevant factors, when platelet counts ≤ 119×109/L, the risk of in-hospital mortality with Cox multivariate model I analysis was (HR3.90, 95% CI 1.67-9.09,P=0.002), with Cox model II was (HR=2.67, 95% CI 1.15 -6.19,P=0.023). Conclusion: AAD patients with admission platelet counts ≤ 119×109/L had the high risk of in-hospital death, even with operation, lower platelet counts was still related to in-hospital death.