Long-term outcomes of posterior release and reduction for irreducible atlantoaxial dislocation / 中华骨科杂志

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.

Improved Glass Bead-Vortex Oscillation Method for DNA Extraction from Diatom / 法医学杂志

OBJECTIVES@#To examine the effect of improving diatom DNA extraction by glass bead - vortex oscillation method.@*METHODS@#The DNeasy PowerSoil Pro kit was used as control, two plant DNA extraction kits with different principles (New Plant genomic DNA extraction kit and Plant DNA Isolation kit) and one whole blood DNA extraction kit (whole blood genomic DNA extraction kit) were selected to extract diatom DNA from lung tissue and water sample of the same drowning case. The combination of mass ratio of glass beads with different sizes and vortex oscillation time was designed, and the optimal DNA extraction conditions were selected with the addition of glass beads oscillation. The extracted products of the conventional group and the modified group were directly electrophoretic and detected by diatom specific PCR. Finally, all the extracts were quantified by qPCR, and the Ct values of different groups were statistically analyzed.@*RESULTS@#When the frequency of vortex oscillation was 3 000 r/min, the optimal combination of DNA extraction was vortex oscillation for 4 min, and the mass ratio of large glass beads to small glass beads was 1∶1. The DNeasy PowerSoil Pro kit was used as a reference, and the Ct value of 10 mL water sample was greater than that of 0.5 g tissue. The Ct values of the other three kits used for plant DNA extraction decreased after the glass beads-vortex oscillation method was used, and the Ct values of the tissues before and after the improvement were statistically significant (P<0.05). The whole blood genomic DNA extraction kit used in this study could successfully extract diatom DNA, the extraction of water samples was close to DNeasy PowerSoil Pro kit, after the modified method was applied to tissue samples, the difference in Ct value was statistically significant (P<0.05). However, when the three kits were used to extract diatom DNA from water samples, Ct values before and after the improvement were only statistically significant in New Plant genomic DNA extraction kit group (P<0.05).@*CONCLUSIONS@#The improved glass bead-vortex oscillation method can improve the extraction efficiency of diatom DNA from forensic materials, especially from tissue samples, by plant and blood DNA extraction kits.

Application Progress of High-Throughput Sequencing Technology in Forensic Diatom Detection / 法医学杂志

Diatom detection is an important method for identifying drowning and throwing corpses after death and inferring the drowning sites in forensic examination of corpses in water. In recent years,high-throughput sequencing technology has achieved rapid development and has been widely used in research related to diatom taxonomic investigations. This paper reviews the research status and prospects of high-throughput sequencing technology and its application in forensic diatom detection.

Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.

Unilateral or bilateral posterior fenestration debridement and bone graft fusion for the treatment of lumbosacral brucellosis spondylitis / 中华骨科杂志

Objective:To analyze the application and clinical efficacy of one-stage unilateral or bilateral fenestration, debridement, interbody fusion combined with posterior internal fixation for the treatment of lumbosacral brucellosis spondylitis.Methods:All patients with lumbosacral brucellosis spondylitis were retrospectively analyzed, who underwent fenestration, debridement, interbody fusion combined with posterior internal fixation from June 2013 to June 2019. A total of 48 patients were enrolled in this study. According to the surgical method, they were divided into two groups. Unilateral fenestration group: 27 cases of one-stage posterior unilateral fenestration, debridement, interbody fusion combined with posterior internal fixation were performed, 21 males and 6 females, aged 23-71 years; Bilateral fenestration group: 21 cases of one-stage posterior bilateral fenestration, debridement, interbody fusion combined with posterior internal fixation were performed, aged 26-58 years. There were 16 males and 5 females. The preoperative and postoperative clinical symptoms, neurological function, C-reactive protein, the surgery duration time, the blood loss, and erythrocyte sedimentation rate were observed. The internal fixation device was evaluated for looseness or fracture by imaging examination. The Bridwell classification criteria were used to evaluate the bone graft fusion. Postoperative complications were also assessed.Results:All patients completed the operation successfully, and the diseased tissues were sent for pathological examination during the operation, and all of them were diagnosed as brucellosis. All patients were followed up for 12-48 months (mean 23.7 ±6.3 months). C-reactive protein, erythrocyte sedimentation rate, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Scores (JOA) were significantly improved in both groups at different time points after operation. There was no significant difference in the general condition before operation between the two groups ( P>0.05). The mean operation time and mean blood loss were 120.5±34.1 min and 214.4±150.2 ml, in the unilateral fenestration group; 187.1±30.3 min and 455.8±250.5 ml in the bilateral fenestration group; and the difference was significant ( t=8.123, t=2.962, P<0.05) . The postoperative lumbar and leg pain were significantly relieved. There was no significant difference in C-reactive protein, erythrocyte sedimentation rate, VAS, ODI and JOA scores between the two groups at the same time point. In the bilateral fenestration group, one patient developed incision infection half a month after the operation, who underwent debridement and drainage, and finally cured. There was no significant difference in the time of bone graft fusion between the two groups ( t=0.542, P>0.05). At the last follow-up, all the patients were completely fused. Conclusion:Unilateral or bilateral fenestration, debridement and bone graft fusion and internal fixation for the treatment of lumbosacral brucellosis spondylitis can achieve good clinical results, and the former has the advantages of short operation time and low cost.

Efficacy of Y type osteotomy in the treatment of severe post-tuberculous thoracolumbar kyphosis / 中华骨科杂志

Objective:To explore the clinical efficacy and surgical indications of Y type osteotomy in the treatment of post-tuberculous thoracolumbar severe angular kyphosis.Methods:From March 2012 to June 2018, 36 patients with post-tuberculous thoracolumbar severe angular kyphosis were treated with Y type osteotomy, including 22 males and 14 females, aged 23.6±5.7 years (range, 7-57 years). The parietal vertebrae of kyphosis were located in the upper thoracic vertebra in 3 cases, the thoracic vertebra in 11 cases, the thoracolumbar segment in 17 cases, and the lumbar vertebra in 5 cases. The Cobb angle of kyphosis before the operation was 92.8°±23.3° (range, 60°-147°). The visual analogue scale (VAS), American Spinal Injury Association (ASIA) neurological function grade, and Kirkaldy-Willis function score were used to evaluate the clinical effect. The imaging evaluation indexes were interbody kyphosis angle and spinal bone fusion.Results:The operation was successful in all the 36 patients. The operation time was 210 ±25.9 min (range, 180-270 min), the intraoperative blood loss was 520 ±110 ml (range, 400-800 ml), and the postoperative follow-up time was 26.38±1.75 months (range, 22-30 months). The postoperative kyphosis Cobb angle was corrected to 16.5°±7.7° (range, 5°-35°), which was significantly improved compared with that before operation( t=25.438, P<0.01), and the correction rate was 82.2%. At the last follow-up, the kyphosis angle was 16.5°±7.1° (range, 6°-32°), which was not significantly different from that after the operation. The preoperative VAS score was 7.3±1.8 (range, 3-9), and the postoperative VAS score was 2.4±0.8 (range, 1-3), while the improvement rate was 67.1%. At the last follow-up, it was 1.1±0.6 (range, 0-2), and the improvement rate was 85.0%. According to the Kirkaldy-Willis functional score, the results were excellent in 25 cases, good in 8 cases, and fair in 3 cases at the last follow-up, with an excellent and good rate of 91.7%. Before the operation, 9 cases were accompanied by neurological dysfunction (ASIA grade: grade C in 2 cases, grade D in 7 cases). At the last follow-up, all the 9 patients recovered to grade E. During the operation, the electrophysiological nerve monitoring was abnormal in 2 patients, and the awakening test was negative in 1 case. In another patient, neuroelectrophysiological monitoring after posterior column osteotomy showed a decrease in bilateral sensory and motor function. There was no compression around the spinal cord in the osteotomy area, so the operating bed was gradually folded and partially restored to kyphosis and temporarily fixed with double rods. Neuroelectrophysiological monitoring suggested the recovery of nerve function. The awakening test showed that the nerve function of both lower limbs recovered close to the preoperative state, and further osteotomy and internal fixation was performed 2 weeks later. The nerve function of both lower limbs returned to normal after 3 months. After the operation, one patient's muscle strength of the lower limbs decreased from grade 5 to grade 3, and the sensory function was normal. After symptomatic support treatment such as neurotrophic drugs, it returned to normal 2 weeks later. 1 case developed delayed neurological dysfunction 1 year after the operation. Neurotrophic drugs and rehabilitation treatment improved it. The sinus of the incision was formed in one case 3 months after the operation and healed after debridement and suture. Conclusion:Y typeosteotomyis a safe and effective method for patients with post-tuberculous thoracolumbar severe angular kyphosis. Compared with traditional osteotomy, anterior support bone grafting can be avoided, and spinal shortening can be reduced.

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2

The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain, named MASCp36, that causes severe acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was 58 PFU in 9-month-old, male BALB/c mice. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three mutations in RBD significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of human ACE2 (hACE2) or mACE2 in complex with the RBD of MASCp36 at 3.1 to 3.7 angstrom resolution elucidates molecular basis for the receptor-binding switch driven by specific amino acid substitutions. Interestingly, N501Y and Q493H enhanced the binding affinity to human ACE2 (hACE2); while triple mutations N501Y/Q493H/K417N decreased affinity to hACE2, thus led to the reduced infectivity of MASCp36 to human cells. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in human and animals. One sentence summaryA mouse adapted SARS-CoV-2 strain that harbored specific amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice.

SARS-CoV-2 infection causes transient olfactory dysfunction in mice

Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowmans gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.

Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 patients

The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, the basis of which remains largely unclear. Currently, though convalescent individuals have been shown with both cellular and humoral immune responses, there is very limited understanding on the immune responses, especially adaptive immune responses, in patients with severe COVID-19. Here, we examined 10 blood samples from COVID-19 patients with acute respiratory distress syndrome (ARDS). The majority of them (70%) mounted SARS-CoV-2-specific humoral immunity with production of neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, accompanied with decreased IFN{gamma} expression in CD4+ T cells in peripheral blood from severe patients. Most notably, we failed in detecting SARS-CoV-2-specific IFN{gamma} production by peripheral blood lymphocytes from these patients. Our work thus indicates that COVID-19 patients with severe symptoms are associated with defective cellular immunity, which not only provides insights on understanding the pathogenesis of COVID-19, but also has implications in developing an effective vaccine to SARS-CoV-2.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.

Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. SummaryThis study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.

An artificial intelligence system reveals liquiritin inhibits SARS-CoV-2 by mimicking type I interferon

The pandemic COVID-19 has spread to all over the world and greatly threatens safety and health of people. COVID-19 is highly infectious and with high mortality rate. As no effective antiviral treatment is currently available, new drugs are urgently needed. We employed transcriptional analysis to uncover potential antiviral drugs from natural products or FDA approved drugs. We found liquiritin significantly inhibit replication of SARS-CoV-2 in Vero E6 cells with EC50 = 2.39 M. Mechanistically, we found liquiritin exerts anti-viral function by mimicking type I interferon. Upregulated genes induced by liquiritin are enriched in GO categories including type I interferon signaling pathway, negative regulation of viral genome replication and etc. In toxicity experiment, no death was observed when treated at dose of 300 mg/kg for a week in ICR mice. All the organ indexes but liver and serum biochemical indexes were normal after treatment. Liquiritin is abundant in licorice tablet (~0.2% by mass), a traditional Chinese medicine. Together, we recommend liquiritin as a competitive candidate for treating COVID-19. We also expect liquiritin to have a broad and potent antiviral function to other viral pathogens, like HBV, HIV and etc.

Potent antiviral effect of protoporphyrin IX and verteporfin on SARS-CoV-2 infection

The SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two FDA-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 M and 0.31 M respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human ACE2. The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2.

Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2

The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

Comparison of efficacy between anterior and posterior combined approach and posterior reduction alone in the treatment of basilar invagination with irreducible atlantoaxial dislocation / 中华骨科杂志

Objective:To compare the clinical efficacy and complications of combined anterior and posterior approach and simple posterior release reduction and internal fixation in the treatment of basilar invagination (BI) with irreducible atlantoaxial dislocation (IAAD) .Methods:The medical records of 47 patients with basilar invaginationdepression complicated with refractory atlantoaxial dislocation who received surgical treatment from July 2000 to December 2017 were retrospectively analyzed. The patients were divided into anterior and posterior combined approach group (23 cases) and posterior approach group (24 cases). Key observation indicators include: Chamberlain line (CL), Wackenheim line (WL), McGae line (ML), atlantodens interval (ADI), cervicomedullary angle (CMA), clivus-canal angle (CCA), JOA scores (Japanese Orthopedic Association, JOA) and Ranawat grade.Results:The average follow-up was 48.7±31.2 months in the A-P group and 44.4±33.4 months in the P group. The average preoperative JOA score of the A-P group was 8.20±2.75 points and 14.98±1.05 points at the last follow-up, and the improvement rate was 77.35%±11.35%. The average preoperative JOA score of the P group was 8.06±2.52 points, and the last follow-up was 14.71±0.62 points, and the improvement rate was 74.38%±10.52%. There was no statistically significant difference between the two groups in JOA score ( t=0.877, P=0.262) and improvement rate ( t=1.478, P=0.206) at the last follow-up. The preoperative CL, WL, ML, ADI, CMA and CCA angles of the A-P group were 13.12±5.76 mm, 6.94±3.55 mm, 7.04±4.57 mm, 9.75±2.06 mm, 110.85°±13.6°, 95.32°±18.3°, respectively. The last follow-up was 1.68±2.53 mm, -2.76±2.26 mm,-1.52±2.43 mm, 1.12±1.55 mm, 149.26°±12.6°, and 141.42°±13.7°, respectively, with statistically significant differences from preoperative. The preoperative CL, WL, ML, ADI, CMA and CCA angles of P group were 12.52±5.17 mm, 6.59±3.04 mm, 6.94±4.32 mm, 9.88±1.93 mm, 115.35°±12.4°, 97.25°±16.4°, respectively. The results of the last follow-up were 2.00±3.67 mm, -3.06±1.85 mm, -1.76±2.88 mm, 1.17±1.18 mm, 146.76°±11.4° and 137.56°±10.4°, respectively, which were statistically significant compared with the preoperative results. There was no significant difference between the two groups in preoperative and final follow-up. The average bone graft fusion time of the A-P group was 9.2±4.9 months, and the average bone graft fusion time of the P group was 9.5±4.7 months. There was no statistically significant difference in the bone graft fusion time between the two groups ( t=0.547, P=0.382). Postoperative complications occurred in a total of 8 cases in the two groups, including 6 cases (21.7%) in the combined approach group and 2 cases (8.3%) in the posterior approach group. The incidence of complications in the posterior approach group was significantly lower than that in the combined approach group. Conclusion:The clinical and imaging results of the treatment of basilar depression with atlantoaxial dislocation by one-stage posterior release reduction and internal fixation are basically the same as those obtained by the anterior and posterior combined approach, but the complication rate of the posterior approach is significantly lower than that of the anterior and posterior combined approach.

Surgical treatment of post-traumatic epiphyseolisthesis at odontoid process in children / 中华骨科杂志

Objective:To evaluated the indications, methods, outcomes and prognosis of surgical treatment for post-traumatic epiphyseolisthesis at odontoid process in children.Methods:Retrospective analysis was performed on 5 cases of children with delayed epiphyseolisthesis of odontoid process in our institution from July 2009 to October 2016, including 1 male and 4 females. Initial surgery age were at1.7~5.4 years old, averaged (39.6±19.4) months and were 0.67-8 months, averaged (87.0±95.1) days. Disease duration ranged from 23 days to 8 months, with an average of 88 days. X-ray, CT and MRI examinations of the occipital-cervical area were taken to evaluate the type of the fracture and the severity of spinal cord compression. Children were treated with anterior loosening combined with posterior fixation fusion or posterior loosening reduction and internal fixation respectively.The function of spinal cord was evaluated by Frankel scale at pre- and post- operation. During the follow-up, X-ray and CT were performed to assess the fusion condition of the grafted bone.Results:The duration of operation was ranged from 75-145 months, with an average of (101.0±20.7) months; Blood loss ranged from 50-100 ml, with an average of (70.0±21.2) ml; follow-up duration ranged from 6 to 48 months, with an average of (23.5±17.6) months. Two cases preoperatively evaluated as Frankel C and D recovered to postoperative Frankel E. Among the five cases, two received satisfactory reduction, two cases received incomplete reduction, and one experienced failure reduction. The epiphyseolisthesis and bone grafted sites achieved solid fusion at 6-15 months after surgery, with an average of (9.5±3.4) months. The physiological curvature of cervical remained well without bone resorption, nonunion, pseudoarthrosis, as well as screw loosening or broken. Internal fixation of 2 cases were removed.Conclusion:Children with post-traumatic epiphyseolisthesis at odontoid process are not common in clinical practice. The detailed diagnosis of medical history, physical examination and comprehensive imaging evaluation. The posterior approach technique of C1-2 was feasible and effective, which could obtain decompression, reconstruction andstability all together.

Influencing factors of health literacy among college students in a university / 中国职业医学

OBJECTIVE: To analyze the status and influencing factors of the health literacy(HL) of college students in a comprehensive university. METHODS: A total of 3 360 students from in a comprehensive university of Xinjiang Production and Construction Corps was selected using multi-stage stratified cluster random sampling method. The HL level of college students was investigated and evaluated with self-edited Xinjiang Construction Corps College Students Health Literacy Questionnaire. RESULTS: The HL level of college students was 17.1%. The HL level of medical students was higher than that of non-medical students(35.4% vs 10.0%, P<0.01). Logistic regression analysis results showed that among the medical students in grade three or four, those with medium and excellent academic achievement, and Han nationality had a positive effect on their HL level(P<0.01). Among the non-medical students, female and medicine related optional courses had a positive effect on their HL level(P<0.05). Students in the sophomore year had a negative effect on their HL level(P<0.05). CONCLUSION: There is a big difference in the level of HL between medical students and non-medical students. Medical college students and non-medical college students have different factors affecting HL, medical education is related to improving HL.