Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

BackgroundSARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. MethodsAll patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. InterpretationMeplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. FundingNational Science and Technology Major Project.

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.

Expression and clinical significance of caudal type homeobox transcription factor-2 in adult acute lymphocytic leukemia / 中国实验血液学杂志

This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.

Total lumbar disc replacement with SB Charité III prosthesis: Chinese experience with more than two years follow-up / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical and radiographic results of total lumbar disc replacement with SB Charité III prosthesis.</p><p><b>METHODS</b>From Dec 1999 to Dec 2006, total lumbar disc replacement with SB Charité III prosthesis was performed in 65 patients affected with degenerative lumbar disc disorders. Among these patients, 48 (52 prosthesis) were followed up for more than two years (from 2.0 to 7.5 years). There were 22 males and 26 females with an average age of 43 years old (from 36 to 58 years). The diagnosis was lumbar disc herniation with low back pain in 34 patients, discogenic low back pain in 9 patients and failed lumbar disc surgery in 5 patients. All patients underwent standard anterior procedure under general anesthesia. One level replacement was done in 44 patients (L3,4 in 3, L4,5 in 23 and L5-S1 in 18), and two level procedures in 4 patients (L3,4/L4,5 in 1 and L4,5/L5-S1 in 3). Clinical and radiographic results of these patients were evaluated at each follow-up time (1, 3, 6, 12, 24 months after operation and the latest).</p><p><b>RESULTS</b>The average visual analogue scales score for pain was 9.3 before operation, changed to 4.3 one month after operation, further declined to 2.6 two years after operation and finally to 1.8 at the latest follow-up evaluation. Meanwhile, the average Oswestry Disability Index was 45.8 before operation, 28.6 one month after operation, 12.5 two years after operation and 8.2 at the latest followup evaluation. All operated levels but one maintained mobile and there was no significant loss of range of motion observed. Complications such as implant dislocation or significant subsidence of the prosthesis occurred in none case of this group. All patients but one (98%) were satisfied with the surgery at the latest follow-up evaluation.</p><p><b>CONCLUSIONS</b>Total lumbar disc replacement is an effective method for the treatment of degenerative disc disorders. Its long-term outcome remains to be verified.</p>