A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions

We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcriptional regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 ({Delta}3678). The {Delta}3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The {Delta}3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the {Delta}3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the {Delta}3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter {Delta}3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that {Delta}3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use.

Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication

SARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this new virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for a cells ability to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of the ARKS motif in histone 3. Orf8 is associated with chromatin, binds to numerous histone-associated proteins, and is itself acetylated within the histone mimic site. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) including H3K9ac, H3K9me3, and H3K27me3 and promotes chromatin compaction while Orf8 lacking the histone mimic motif does not. Further, SARS-CoV-2 infection in human cell lines and postmortem patient lung tissue cause these same disruptions to chromatin. However, deletion of the Orf8 gene from SARS-CoV-2 largely blocks its ability to disrupt host-cell chromatin indicating that Orf8 is responsible for these effects. Finally, deletion of the ORF8 gene affects the host-cell transcriptional response to SARS-CoV-2 infection in multiple cell types and decreases the replication of SARS-CoV-2 in human induced pluripotent stem cell-derived lung alveolar type 2 (iAT2) pulmonary cells. These findings demonstrate a novel function for the poorly understood ORF8-encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Finally, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.

The N501Y spike substitution enhances SARS-CoV-2 transmission

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.

Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail

The SARS-CoV-2 pandemic has led to an urgent need to understand the molecular basis for immune recognition of SARS-CoV-2 spike (S) glycoprotein antigenic sites. To define the genetic and structural basis for SARS-CoV-2 neutralization, we determined the structures of two human monoclonal antibodies COV2-2196 and COV2-21301, which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor binding domain (RBD) of SARS-CoV-2. COV2-2196 forms an "aromatic cage" at the heavy/light chain interface using germline-encoded residues in complementarity determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals1-4. The structure of COV2-2130 reveals that an unusually long LCDR1 and HCDR3 make interactions with the opposite face of the RBD from that of COV2-2196. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the critical residues of both antibodies and identified positions of concern for possible viral escape. Nonetheless, both COV2-2196 and COV2-2130 showed strong neutralizing activity against SARS-CoV-2 strain with recent variations of concern including E484K, N501Y, and D614G substitutions. These studies reveal germline-encoded antibody features enabling recognition of the RBD and demonstrate the activity of a cocktail like AZD7442 in preventing escape from emerging variant viruses.

Neutralization of spike 69/70 deletion, E484K, and N501Y SARS-CoV-2 by BNT162b2 vaccine-elicited sera

We engineered three SARS-CoV-2 viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion+N501Y+D614G from UK; and E484K+N501Y+D614G from SA. Neutralization geometric mean titers (GMTs) of twenty BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.

A trans-complementation system for SARS-CoV-2

The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research and countermeasure development. Here we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components: a genomic viral RNA containing a deletion of ORF3 and envelope gene, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. The results suggest that the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.

Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility

A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 replication on human lung epithelial cells and primary human airway tissues, through an improved infectivity of virions with the spike receptor-binding domain in an "up" conformation for binding to ACE2 receptor. Hamsters infected with D614 or G614 variants developed similar levels of weight loss. However, the G614 virus produced higher infectious titers in the nasal washes and trachea, but not lungs, than the D614 virus. The hamster results confirm clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. For antibody neutralization, sera from D614 virus-infected hamsters consistently exhibit higher neutralization titers against G614 virus than those against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus before clinical development. ImportanceUnderstanding the evolution of SARS-CoV-2 during the COVID-19 pandemic is essential for disease control and prevention. A spike protein mutation D614G emerged and became dominant soon after the pandemic started. By engineering the D614G mutation into an authentic wild-type SARS-CoV-2 strain, we demonstrate the importance of this mutation to (i) enhanced viral replication on human lung epithelial cells and primary human airway tissues, (ii) improved viral fitness in the upper airway of infected hamsters, and (iii) increased susceptibility to neutralization. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis

SARS-CoV-2 has resulted in a global pandemic and shutdown economies around the world. Sequence analysis indicates that the novel coronavirus (CoV) has an insertion of a furin cleavage site (PRRAR) in its spike protein. Absent in other group 2B CoVs, the insertion may be a key factor in the replication and virulence of SARS-CoV-2. To explore this question, we generated a SARS-CoV-2 mutant lacking the furin cleavage site ({Delta}PRRA) in the spike protein. This mutant virus replicated with faster kinetics and improved fitness in Vero E6 cells. The mutant virus also had reduced spike protein processing as compared to wild-type SARS-CoV-2. In contrast, the {Delta}PRRA had reduced replication in Calu3 cells, a human respiratory cell line, and had attenuated disease in a hamster pathogenesis model. Despite the reduced disease, the {Delta}PRRA mutant offered robust protection from SARS-CoV-2 rechallenge. Importantly, plaque reduction neutralization tests (PRNT50) with COVID-19 patient sera and monoclonal antibodies against the receptor-binding domain found a shift, with the mutant virus resulting in consistently reduced PRNT50 titers. Together, these results demonstrate a critical role for the furin cleavage site insertion in SARS-CoV-2 replication and pathogenesis. In addition, these findings illustrate the importance of this insertion in evaluating neutralization and other downstream SARS-CoV-2 assays. ImportanceAs COVID-19 has impacted the world, understanding how SARS-CoV-2 replicates and causes virulence offers potential pathways to disrupt its disease. By removing the furin cleavage site, we demonstrate the importance of this insertion to SARS-CoV-2 replication and pathogenesis. In addition, the findings with Vero cells indicate the likelihood of cell culture adaptations in virus stocks that can influence reagent generation and interpretation of a wide range of data including neutralization and drug efficacy. Overall, our work highlights the importance of this key motif in SARS-CoV-2 infection and pathogenesis. Article SummaryA deletion of the furin cleavage site in SARS-CoV-2 amplifies replication in Vero cells, but attenuates replication in respiratory cells and pathogenesis in vivo. Loss of the furin site also reduces susceptibility to neutralization in vitro.

A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19

A high-throughput platform would greatly facilitate COVID-19 serological testing and antiviral screening. Here we report a nanoluciferase SARS-CoV-2 (SARS-CoV-2-Nluc) that is genetically stable and replicates similarly to the wild-type virus in cell culture. We demonstrate that the optimized reporter virus assay in Vero E6 cells can be used to measure neutralizing antibody activity in patient sera and produces results in concordance with a plaque reduction neutralization test (PRNT). Compared with the low-throughput PRNT (3 days), the SARS-CoV-2-Nluc assay has substantially shorter turnaround time (5 hours) with a high-throughput testing capacity. Thus, the assay can be readily deployed for large-scale vaccine evaluation and neutralizing antibody testing in humans. Additionally, we developed a high-throughput antiviral assay using SARS-CoV-2-Nluc infection of A549 cells expressing human ACE2 receptor (A549-hACE2). When tested against this reporter virus, remdesivir exhibited substantially more potent activity in A549-hACE2 cells compared to Vero E6 cells (EC50 0.115 vs 1.28 M), while this difference was not observed for chloroquine (EC50 1.32 vs 3.52 M), underscoring the importance of selecting appropriate cells for antiviral testing. Using the optimized SARS-CoV-2-Nluc assay, we evaluated a collection of approved and investigational antivirals and other anti-infective drugs. Nelfinavir, rupintrivir, and cobicistat were identified as the most selective inhibitors of SARS-CoV-2-Nluc (EC50 0.77 to 2.74 M). In contrast, most of the clinically approved antivirals, including tenofovir alafenamide, emtricitabine, sofosbuvir, ledipasvir, and velpatasvir were inactive at concentrations up to 10 M. Collectively, this high-throughput platform represents a reliable tool for rapid neutralization testing and antiviral screening for SARS-CoV-2.

Analysis of radiotherapy curative effect and prognostic factors in 164 patients with extracranial oligometastases / 中华放射肿瘤学杂志

Objective To investigate the efficacy of radiotherapy,as well as the prognostic factors of survival in patients with extracranial oligometastases. Methods A total of 164 patients who underwent intensity-modulated radiotherapy ( IMRT ) of the extracranial oligometastases, from January 2013 to December 2016, were enrolled in the study. The short-term efficacy, local control rate, overall survival, progression free survival and adverse effects of treatment were observed. Results Short-term efficacy was assessed within the first 1-3 months after the end of radiotherapy. The objective response rate (CR+PR) was 78. 7% and the short-term efficacy is mainly related to the T stage of primary tumor ( P＝0. 004).Until the last follow-up,all patients with 1-,2-and 3-year LC were 89. 8%,82. 5% and 74. 9% respectively.Univariate analysis showed that the influencing factors of LC include tumor size and gross tumor volume dose ( all P＜0. 05),multivariate analysis found no significant influence factors. The 1-,2- and 3-year OS were 83. 4%, 69. 6% and 54. 6% respectively. Univariate and multivariate analysis showed that the primary tumor sources, metastasis organs,whether synchronous or adjuvant chemotherapy and short-term efficacy were independent prognostic factors in patients of OS ( P＜0. 05 ).Main toxicity-associated events were grade 1-2 acute reactions,with only 6 patients experiencing grade 3 toxicity;no grade≥4 toxic reactions or treatment-related deaths occurred. Conclusions Radiation therapy for the treatment of extracranial oligometastases can achieve good curative effect,is well-tolerated and has low toxicity.

A wearable ballistocardiogram-electrocardiogram union acquisition system / 生物医学工程学杂志

Ballistocardiogram (BCG) and electrocardiogram (ECG) can realize the detection of cardiac function from mechanical and electrical dimensions respectively. By extracting the corresponding characteristic parameters of the two signals and carrying out joint analysis, an important cardiac physiological index such as cardiac contractility, can be reflected. To overcome the shortcomings of complication and heaviness of the existing acquisition equipment, a wearable BCG-ECG signal acquisition system is designed in this paper, which realizes BCG signal acquisition based on accelerometer and ECG signal acquisition based on conductive rubber electrodes. The signals of 6 healthy persons were collected, and BCG signals collected by piezoelectric films were used as reference signals. The waveform characteristics of signals were compared, and the difference of cardiac cycle acquisition was analyzed. The waveform characteristics of the two signals acquired by the device were consistent with the standard signals, and there was no significant difference in the acquisition of the cardiac cycle between the proposed method and the traditional method. The results show that the system can accurately collect human BCG signals and ECG signals. The system provides a basis for subsequent research on BCG signal formation mechanism and health applications.

Correlation between neutrophil to lymphocyte ratio and cerebral microbleeds in patients with ischemic stroke / 国际脑血管病杂志

ObjectiveTo investigate the correlation between neutrophil to lymphocyte ratio (NLR) and cerebral microbleeds (CMBs) in patients with acute ischemic stroke.MethodsThe consecutive inpatients with acute ischemic stroke were prospectively enrolled.Gradient echo-T2*-weighted imaging was used to evaluate CMBs and their quantity.Univariate analysis was used to compare the baseline data between the CMB group and the non-CMB group.Multivariable logistic regression analysis was used to identify the independent correlation between NLR and CMBs.ResultsA total of 218 patients with acute ischemic stroke were prospectively enrolled, including 66 (30.3%) with CMBs.The age (64.7±6.6 years vs.66.9±8.6 years;t=2.052, P=0.041), high sensitive C-reactive protein (7.0[2.3-13.9] mg/L vs.8.9[4.0-28.1] mg/L;Z=2.008, P=0.045) and NLR (1.9[1.4-2.9] vs.2.3[1.7-3.6];Z=2.071, P=0.038) in the non-CMB group were significantly lower than those of the CMB group.Multivariate logistic regression analysis showed that NLR (odds ratio 1.276, 95% confidence interval 1.008-1.670;P=0.045) and age (odds ratio 1.044, 95% confidence interval 1.002-1.087;P=0.040) were the independent risk factor for CMBs.Spearman correlation analysis showed that NLR was significantly positively correlated with the severity of CMBs (r=0.210, P=0.007).ConclusionsIn patients with acute ischemic stroke, NLR was associated with CMBs and their severity, suggesting that inflammatory reaction might be involved in the occurrence of CMBs.

Comparison of heart rate variability measurements between ballistocardiogram and electrocardiography / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the heart rate variability (HRV) measurements between ballistocardiogram (BCG) and electrocardiography (ECG).</p><p><b>METHODS</b>The signals of BCG and ECG of 21 patients were collected synchronously. JJ intervals of BCG and RR intervals of ECG were used to calculate the cardiac periods. The parameters of HRV analysis were calculated in time domain analysis, frequency domain analysis and nonlinear analysis. The results derived from BCG and ECG were compared.</p><p><b>RESULTS</b>The parameters of HRV analysis calculated from BCG and ECG had high similarity. The correlation coefficients of SDNN, TP, LF, HF and SD2 between the BCG and ECG methods were high (r = 1). The correlation coefficients of rMSSD and SD2 were 0.99 and of PNN50 and LF/HF were 0.98 between the two methods. HRV analysis results derived from the two methods were similar (P > 0.05).</p><p><b>CONCLUSION</b>HRV could also be measured reliably by calculating the JJ interval from BCG.</p>

Research on effect of endoscopic submucosal tunnel dissection on patients with large esophageal superficial neoplasms / 中国医学装备

Objective:To analyze the effect of endoscopic submucosal tunnel dissection on patients with large esophageal superficial neoplasms.Methods: Chosen patients with large esophageal superficial neoplasms in our hospital as research object, randomly divided into control group treated by endoscopic mucosal dissection (ESD) and observation group treated by endoscopic submucosal tunnel dissection(ESTD), compared surgery related indicators, complications and treatment outcomes.Results: 1)Observation group patients’ tumor stripping rate (23.17±4.73)/min was significantly higher than control group patients’ (12.65±2.19)/min; Intraoperative blood loss(9.14±0.67)ml, total length of hospital stay (7.34±1.89) d, were significantly less than control group patients with intraoperative blood loss(21.38±3.14)ml, total length of hospital stay (13.21±3.05)d, t value was 4.965, 5.395, 4.932, respectively(t=4.965,t=5.395,t=4.932;P<0.05); 2)Observation group patients esophageal bleeding ESTD rate(5.26%), esophageal stricture rate(31.58%), mediastinal emphysema rate(5.26%), esophageal perforation rate of 0, were significantly less than control group patients with esophageal bleeding rate(31.58%), esophageal stricture rate(5.26%), mediastinal emphysema rate(21.05%), esophageal perforation rate (26.32%), t value were 4.378, 4.378, 4.471, 5.758, (t=4.378,t=4.378,t=4.471,t=5.758;P<0.05); 3)Observation group patients with no recurrence during the follow-up period, control group patients with local recurrence rate of 21.05%, t value 8.623,P<0.05(t=8.623, P<0.05).Conclusion: Endoscopic tunnel mucosal stripping technique can effectively improve the complete tumor removal rate, during the process of optimization operation at the same time reduce the occurrence of complications, to the improvement of the prognosis of patients with positive clinical significance.

Study on dosimetric verification of VMAT treatment planning for chest esophageal carcinoma / 中华放射肿瘤学杂志

Objective To study the dosimetry characteristics of VMAT plan in the esophageal carcinoma radiotherapy.Methods Application of 0.6 cm3 ionization chamber and COMPASS threedimensional dose verification system,20 cases of upper and middle chest esophageal carcinoma on the VMAT plans for absolute dose and relative dose verification.Dose volume histogram (DVH) comparison treatment target,lungs,heart,and differences in the spinal cord irradiation dose and volume,and analyses γpass rate of GTV,CTV,PTV and organs at risks.Results The center dose of upper and middle chest esophageal carcinoma accurate rates were above 99％.Thoracic segment esophageal:GTV,PTV and organs at risks of γ pass rate above 97％.D95％ and Dmean of GTV,CTV and PTV were relatively undervalued within 3％.D1％ of spinal cord is 2.21％ overvalued.Left and right pulmonary V5 were slightly overvalued by about 0.5％,V10-D30,Dmean undervalued within 2％.In period of middle chest esophageal carcinoma:the gamma passed rate of GTV,CTV,PTV and organs at risks of above 97％,GTV,CTV,PTV D95％,Dmean were relatively undervalued within 2％.Spinal cord D1％ is 2.04％ overvalued.Left and right pulmonary V5-D30 to V10 as a trend of gradually to be underestimated,at 1.5％.Heart Dmean was undervalued by 2.68％.Conclusion VMAT technology is applicable in the chest esophageal carcinoma radiotherapy.

Pedicle screw bi-cortical fixation in treating lumbar spondylolisthesis or destabilization in aged people / 中国组织工程研究

OBJECTIVE: To investigate feasibility and effectiveness of pedicle screw bi-cortical fixation in lumbar spondylolisthesis or destabilization of aged people. METHODS: The statistical significance of the distance between the anterior edge of vertebral body and the anterior major blood vessels at the level of pediculus arcus vertebrae by CT scan at random were measured and analyzed. 82 cases of lumbar spondylolisthesis or destabilization, aged 65 years (range 51 to 75 years), including 35 males and 47 females, were treated pedicle screw bi-cortical fixation, with the anterior edge of the vertebral body penetrated by one screw thread. The function was evaluated by Macnab backleg pain scale standards. RESULTS: There was significant difference in the distance of the anterior edge and the major vessels between the old and the young (P< 0.05). All the 82 cases were operated successfully, and the mean time was 145 minutes and the mean amount of bleeding was 530 mL. The 43 cases including 15 males and 28 females were followed up for 18 months (range 3 to 53 months). There was one case of rupture of the spinal dura mater with no sequela after the suture. There were 3 cases of transient paralysis and pain of lower limbs, which were alleviated after 2 months' treatment. No complications of nerve root or vessel injuries were found. All incisions healed well at the primary stage. The lumbocrural pain of all 43 cases was alleviated to a certain content. There were 31 cases of excellent, 10 of good, and 2 of fair; the excellent and good rate was 97%. CONCLUSION: It is feasible and safe to treat the lumbar spondylolisthesis or destabilization in the old with the pedicle screw bi-cortical fixation.