Computation of Antigenicity Predicts SARS-CoV-2 Vaccine Breakthrough Variants

It has been reported that multiple SARS-CoV-2 variants of concerns (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) can reduce neutralisation by antibodies, resulting in vaccine breakthrough infections. Virus-antiserum neutralisation assays are typically performed to monitor potential vaccine breakthrough strains. However, such experimental-based methods are slow and cannot instantly validate whether newly emerging variants can break through current vaccines or therapeutic antibodies. To address this, we sought to establish a computational model to predict the antigenicity of SARS-CoV-2 variants by sequence alone and in real time. In this study, we firstly identified the relationship between the antigenic difference transformed from the amino acid sequence and the antigenic distance from the neutralisation titres. Based on this correlation, we obtained a computational model for the receptor binding domain (RBD) of the spike protein to predict the fold decrease in virus-antiserum neutralisation titres with high accuracy (~0.79). Our predicted results were comparable with experimental neutralisation titres of variants, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.429 (Epsilon), P.1 (Gamma), B.1.526 (Iota), B.1.617.1 (Kappa), and C.37 (Lambda), as well as SARS-CoV. Here, we firstly predicted the fold of decrease of B.1.1.529 (Omicron) as 17.4-fold less susceptible to neutralisation. We visualised all 1521 SARS-CoV-2 lineages to indicate variants including B.1.621 (Mu), B.1.630, B.1.633, B.1.649, and C.1.2, which can induce vaccine breakthrough infections in addition to reported VOCs B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our study offers a quick approach to predict the antigenicity of SARS-CoV-2 variants as soon as they emerge. Furthermore, this approach can facilitate future vaccine updates to cover all major variants. An online version can be accessed at http://jdlab.online.

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health, and imposes severe burdens on the entire human society. The severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause severe respiratory illness and death. Currently, there are no specific antiviral drugs that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively developed by research groups around the world. The surface S (spike) protein and the highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely considered as promising candidates for vaccines. In order to guide the design of an effective vaccine, we need experimental data on these potential epitope candidates. In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.

Risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing.</p><p><b>METHODS</b>A total of 1 236 infants and young children who experienced a first wheezing episode and were hospitalized between August 2014 and February 2015 were enrolled, among whom 387 were allergic to dust mites. These infants and young children were followed up to 1 year after discharge. A total of 67 infants and young children who experienced 3 or more recurrent wheezing episodes within 1 year were enrolled as the recurrent wheezing group, while 84 infants and young children who did not experience recurrent wheezing during follow-up were enrolled as the control group. Univariate analysis and multivariate logistic stepwise regression analysis were performed to investigate the risk factors for recurrent wheezing in these patients.</p><p><b>RESULTS</b>The univariate analysis showed that the age on admission, wheezing time before admission, Mycoplasma pneumoniae infection rate, and influenza virus infection rate were associated with recurrent wheezing. The multivariate logistic stepwise regression analysis showed that the older age on admission (OR=2.21, P=0.04) and Mycoplasma pneumoniae infection (OR=3.54, P=0.001) were independent risk factors for recurrent wheezing.</p><p><b>CONCLUSIONS</b>Infants and young children who are allergic to dust mites, especially young children, have a significantly increased risk of recurrent wheezing if they are complicated by Mycoplasma pneumoniae infection during the first wheezing episode.</p>

Case-control study on influence of femoral neck fracture on deep venous thrombosis in patients undergoing prosthetic hip surgery / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the association between femoral neck fracture and deep vein thrombosis (DVT) in patients undergoing prosthetic hip surgery.</p><p><b>METHODS</b>The data of patients who underwent prosthetic hip surgery from January 2005 to July 2010 were collected, the cases were included into the study after exclusion of those could not be suitable for the study. The patients with diagnosis of deep-vein thrombosis (DVT) were identified together as the case group, and the patients without DVT were selected randomly and matched with frequency as the control group. The matching characteristics included age, gender and body weight. The patients with femoral neck fracture were counted in both case and control group. The odds ratio was calculated and the exposure rate of both group were compared.</p><p><b>RESULTS</b>There were total 670 patients underwent prosthetic hip surgery during the period, and after exclusion,the data of 408 patients were collected into the study. There were 13 patients in the case group (4 males and 9 females, ranging in age fram 57 to 91 years), all of them suffering from femoral neck fracture and the exposure rate was 100.0% (13/13). There were 52 patients in the control group (18 males and 34 females, ranging in age from 57 to 91 years), 39 of them suffering from femoral neck fracture, the exposure rate was 75.0% (39/52); there was no statistically significant difference in exposure rate of two groups.</p><p><b>CONCLUSION</b>The diagnosis of femoral neck fracture is not the independent risk factor for postoperative DVT of prosthetic hip surgery. The epidemiologic characteristics of femoral neck fracture indicate that the patients are in high risk of DVT, who meanwhile are the most of patients undergoing the prosthetic hip surgery. Though the surgery itself is a risk of DVT, it can reduce the risks for patients with femoral neck fracture through some therapeutic effects.</p>

Construction of HCV-producing cell model based on self-cleaving ribozyme / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To construct a stable HCV-producing cell model for anti-HCV drug research.</p><p><b>METHODS</b>The HCV-ribozyme recombinant plasmid pJFH1-Rbz was constructed to generate the exact 5' and 3' ends of HCV genomic RNA by placing two self-cleaving ribozymes at both ends of the HCV JFH-1 cDNA. The plasmid was then transfected into HepG2 cells and the resultant clones were screened with G418. Subsequently, immunofluorescence and Western blot were performed to detect the expression of HCV core protein, HCV RNA level was quantitated by TaqMan real-time PCR method and HCV particles was detected by electron microscopy.</p><p><b>RESULTS</b>HCV core protein was detected in the screened cell clone, and the level of HCV RNA was up to 1000,0000 copies/ml in the culture medium. Electron microscopy showed the viral particles in the culture suspension were approximately 55 nm in diameter. IFN-treating experiment demonstrated that the HCV RNA level decreased with the increasing concentration of IFN alpha.</p><p><b>CONCLUSION</b>We constructed a stable HCV-producing cell model which can be used for anti-HCV drug research.</p>

Combined external skeletal fixation instrumentation with locked intramedullary nailing for tibia lengthening / 中华外科杂志

<p><b>OBJECTIVE</b>To shorten the time of external skeletal fixation on legs, and enhance quality of limb lengthening, avoid complications of shortening, bending, twisting and etc.</p><p><b>METHODS</b>Insert pin transcortical to attack external skeletal fixation simultaneously, put un-reaming locked intramedullary nail (do not insert distal locked screw) into endosteum of lengthening bone. After the legs achieved predetermined length, insert distal locked screw and then remove external skeletal fixation, locked intramedullary nail, then maintain consolidation of rehabilitation.</p><p><b>RESULTS</b>The group lengthened legs for 412 cases. The range of lengthening was 3 to 18 cm. Mean length was 7.6 cm. The mean time for needed external skeletal fixation was 20 d/cm. The mean time of osteogenesis was 56 d/cm. For complications, there were 3 tibias ununion cases and 1 varus ankle. All cases were treated undergoing twice.</p><p><b>CONCLUSIONS</b>The method reduces the time for needed external skeletal fixation visibly, enhances the quality of limb lengthening remarkably, prevents complications of shortening new bone, deformity, bending and re-fracture which do not effect the healing time. This is a new choice of limb lengthening.</p>