Objective To construct secretory IgA(sIgA)based on the previously screened IgG neutralizing antibody ZW2G10 against SARS-CoV-2,evaluate its activity and find out about the biodistribution of sIgA in ICR mice after nasal administration.Methods After expression,purification,and identification,sIgA was evaluated for its binding and neutralizing activity through ELISA and pseudovirus-based neutralization assays.SIgA was coupled with Alexa Fluor 750 dye and administered to mice via nasal administration.In vivo imaging was used to observe the biodistribution of sIgA.After dissection of the mice,the biodistribution of sIgA in various tissues and organs was observed.Results Compared with IgG,sIgA retained the binding ability to SARS-CoV-2 S proteins,and its neutralizing ability was enhanced.After nasal administration of a single dose of 1 mg/kg,sIgA could be retained in the lungs of mice for more than 72 hours.SIgA could be detected only in the nasal cavity and gastrointestinal tract within 8 h of administration,but not in the heart,liver,kidney,spleen,brain,bladder or blood.Conclusion In this study,a universal and efficient sIgA expression system has been established.sIgA can effectively target the respiratory tract and lungs after nasal administration.SIgA is expected to become a potential drug that provides immediate passive immune protection.

Given the increasing exploitation of antibodies in different contexts such as molecular diagnostics and therapeutics, it would be beneficial to unravel properties of antigen-antibody interaction with modeling of computational protein-protein docking, especially, in the absence of a cocrystal structure. However, obtaining a native-like antigen-antibody structure remains challenging due in part to failing to reliably discriminate accurate from inaccurate structures among tens of thousands of decoys after computational docking with existing scoring function. We hypothesized that some important physicochemical and energetic features could be used to describe antigen-antibody interfaces and identify native-like antigen-antibody structure. We prepared a dataset, a subset of Protein-Protein Docking Benchmark Version 4.0, comprising 37 nonredundant 3D structures of antigen-antibody complexes, and used it to train and test multivariate logistic regression equation which took several important physicochemical and energetic features of decoys as dependent variables. Our results indicate that the ability to identify native-like structures of our method is superior to ZRANK and ZDOCK score for the subset of antigen-antibody complexes. And then, we use our method in workflow of predicting epitope of anti-Ebola glycoprotein monoclonal antibody-4G7 and identify three accurate residues in its epitope.

Objective To analyze the incidence and risk factors of contralateral radiculopathy in patients after unilateral transforaminal lumbar interbody fusion (TLIF) surgery.Methods A retrospective study was conducted within 587 patients (average age 57.1 years,range 19-71 years) who underwent unilateral TILF from January 2010 to January 2014 in our hospital,including 334 males and 253 females.Patients were divided into a symptomatic group and an asymptomatic group.The causes of contralateral neurological symptom were evaluated according to the radiological data.The difference of pre-and post-operative contralateral foramen area (CFA),segmental angle (SA) and the clinical treatment outcomes (VAS,JOA score) were compared between two groups.Results Patients were followed up for 9-21 months,average 15.1 months.Post-operative contralateral radiculopathy occurred in 28 (4.8％) of the patients who underwent unilateral TLIF,including contralateral foraminal stenosis in 16 (57.1％,16/28),screw malposition in 5 (17.9％,5/28),contralateral lateral recess stenosis and/or newly developed disc herniation in 3 (10.7％,3/28),hematoma in 1 (3.6％,1/28),cement compression in 1 (3.6％,1/28),and unknown origin in 2 patients (7.1％,2/28).Nineteen (3.2％,19/587) of the 28 patients received revision surgery because of ineffective conservative treatment.Compared with the asymptomatic group,the difference of pre-and post-operative CFA was significantly smaller (-13.8±13.2 mm2) in symptomatic group,while the SA was significantly greater (7.0°±9.8°) in symptomatic group.The JOA score at 3 months after the surgery was significantly improved in asymptomatic group (63.0％±18.1％,P＜0.05).Conclusion The incidence rate of contralateral neurological symptom was 4.8％ in the present study.The potential risk factors associated with contralateral radiculopathy were predominantly contralateral foraminal stenosis and screw malposition.The excessive restoration of SA might have an effect on contralateral nerve compression,which should arouse the attention of the surgeon.

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

Complete burst fractures of the L₅ is relatively uncommon. How to accomplish a rigid internal fixation as well as preserve motor function is an enormous challenge. We report such a case treated via a single posterior vertebrectomy with 270-degree decompression and reconstruction using titanium mesh cage. The disc between L₅/S₁ was preserved by placing the titanium mesh cage on the inferior endplate of the L₅. We hope this method can offer a possible solution for other surgeons when they meet a similar fracture pattern.
Adult ; Decompression, Surgical ; Fracture Fixation, Internal ; instrumentation ; methods ; Humans ; Internal Fixators ; Male ; Spinal Fractures ; surgery ; Surgical Mesh ; Titanium

Objective To develop a three-dimensional finite element model of atlantoaxial instability and compare the biomechanical properties of percutaneous anterior transarticular screw (ATS) and posterior transarticular screw (PTS) fixations.Methods A pathologic three-dimensional finite element model of atlantoaxial instability was developed from CT images of the upper cervical spine of volunteers with the aid of softwares,such as Mimics,Freeform,and Ansys.Percutaneous C1-2 ATS and PTS fixation modes were simulated and implanted to the model.Under the preload of 40 N and force moment of 1.5 Nm in anterior flexion,posterior extension,lateral bending,and axial rotation,biomechanical properties of the two fixation modes were compared.Results Under the four loading modalities,both fixation techniques provided maximal inhibition on C1-2 movement.The maximal stress for ATS was larger than that for PTS and maximal displacement for ATS was smaller than that for PTS.Conclusions Both ATS and PTS provide similar outlook and are effective to stabilize the atlantoaxial joint.Biomechanical performance of percutaneous C1-2 ATS is better than that of percutaneous C1-2 PTS.

Objective To investigate complications associated with Coflex interspinous process device for degenerative lumbar disc diseases and methods to treat.Methods Clinical data of 121 patients with degenerative lumbar disc diseases,who had undergone surgical decompression and additional fixation of Coflex between November 2007 and June 2011,was analyzed retrospectively.There were 76 males and 45 females,aged from 37 to 75 years (average,54.6 years).Surgery-related complications and sequelae were recorded and analyzed.Results Surgery-related complications occurred in 10 patients,and the incidence was 8.3％ (10/121).There were 3 cases of device-related complications,including wing break in 1 case,prosthetic loosening in 1 case and spinal process fracture in 1 case; all 3 cases were treated conservatively and received good results.There were 7 cases of non-device-related complications,including dura mater dilaceration in 2 cases,superficial wound infection in 1 case,insufficient decompression of spinal canal in 2 cases,recurrence of disc herniation in 1 case,and intraspinal hematoma in 1 case; the former 3 patients recovered after corresponding treatment,and the latter 4 patients also recovered after re-operation.Conclusion The incidences of complications and re-operation associated with application of Coflex are low,and the incidence of device-related complications is also low.The precise intraoperative manipulation is the key to reduce incidence of device-related complications.It's absolutely necessary to strictly master surgical indications and perform sufficient decompression in order to receive good surgical results and avoid non-device-related complications.

ObjectiveTo study the effect of angiotensin Ⅱ type 1 receptor antagonist (ARB) losartan on reducing the incidence of stroke in patients which suffer from hypertension and atrial fibrillation(AF).MethodsProspective randomized analysis was used to divide one hundred and eighty hypertemion patients with atrial fibrillation into two groups.ARB treatment group was treated with losartan (n =90) and beta-blockers treatment group was treated with metoprolol ( n =90),all patients were treated for three years and followed up.Blood pressure,pulse pressure,incidence of stroke and myocardial infarction and mortality of cardiovascular events were evaluated.ResultsAfter antihypertensive treatment,blood pressure was reduced in two groups,the pulse pressure in losartan group was reduced obviously( all P ＜0.01 ).The incidence of stroke and myocardial infarction and mortality of cardiovascular events in losartan group were 22.2％,10.0％ and 13.3％,respectively,lower than that in metoprolol group 70.0％,40.0％ and 44.4％ ( all P ＜0.01 ).ConclusionLosartan reduced the incidence of stroke in the hypertension patients with AF.

Monoclonal antibodies (mAbs) contribute a lot to the development of numerous fields in life science as a pivotal tool in modern biological research. Development of the PCR methods and maturation of antibody production have made it possible to generate mAbs from single human B cells by single cell RT-PCR with successional cloning and expression in vitro. Compared to traditional monoclonal antibody technologies, single B cell technologies require relatively fewer cells, which are highly efficient in obtaining specific mAbs in a rapid way with preservation of the natural heavy and light chain pairing. With so many advantages, single B cell technologies have been proved to be an attractive approach for retrieval of naive and antigen-experienced antibody repertoires generated in vivo, design of rationale structure-based vaccine, evaluation and development of basic B cell biology concepts in health and autoimmunity, and prevention of infectious diseases by passive immunization and therapy for disorders. Accordingly, this review introduced recent progresses in the single B cell technologies for generating monoclonal antibodies and applications.
Antibodies, Monoclonal ; biosynthesis ; genetics ; immunology ; Antibody Specificity ; B-Lymphocytes ; cytology ; immunology ; metabolism ; Humans ; Immunologic Techniques

Objective To evaluate the mid-term clinical effects and the imaging changes of Coflex interspinous dynamic internal fixation for low back pain. Methods From February 2007 to June 2009,Coflex interspinous dynamic internal fixation was performed in a consecutive 45 patients. They included 26 males and 19 females, with an average of 51.4 years ranging in age from 45 to 70 years. Thirty-two cases were in L4.5 level, 11 in L5S1 level and 2 in both two levels. The patients were treated with limited laminectomy and implanted with Coflex device. Clinical outcomes were assessed by Oswestry disability index (ODI)scores and Japanese Orthopaedic Association (JOA) questionnaires before and after operation. The imaging examination was obtained to assess height of the intervertebral space, area of the intervertebral foramen,segment movement of the operation level, low lumbar curvature and signal of the lumbar disc on MRI. Results The follow-up time ranged from 10 to 34 months, with an average of 24 months. The ODI scores decreased significantly from 62.82±10.42 preoperatively to 11.80±3.35 postoperatively. The JOA scores were improved remarkably from 9.00±2.63 preoperatively to 24.65±1.86 postoperatively. The proportion with optimal effect was 89% (40 cases). The Cobb angle after operation of L4.5 and L5S1 level was 15.1°±3.9° and 16.3°±3.8° respectively, which was significantly decreased after operation. The range of motion of the L4.5 level increased from 6.5°±1.5° to 8.4°±2.6° while the L5S1 level did not change notedly. The heights of the dorsal intervertebral disc, distance of the spinous processes, intervertebral foramen height and area were significantly higher than those before operation. Conclusion The Coflex interspinous dynamic internal fixation is available to reserve segment movement, to increase intervertebral space height and foramen area. Meanwhile,it is effective to self-repair and prevent degeneration for the disc in adjacent levels.