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.

Host contributions to Ebola virus replication, transcription and translation:research advances / 军事医学

Ebola virus(EBOV) disease,the fatality rate of which is as high as 25％-90％,can be transmitted by contac t between human and non-human primates.Early studies of the virus focused on the functions of viral proteins.Recently,the focus of research of EBOV has been switched to the host interaction factors during the process of virus reproduction.In this review,advances in studies on host contributions to EBOV replication,transcription and translation are summarized in order to enhance our understanding of contributions of the host to the virus reproduction process and provide reference for research strategies and new antiviral drugs.

Imaging features of active Crohn′s disease on conventional ultrasound and contrast-enhanced ultrasound / 中华医学超声杂志（电子版）

Objective To investigate the imaging features of active Crohn′s disease on conventional ultrasound and contrast-enhanced ultrasound (CEUS). Methods The imaging features of 20 patients with an established diagnosis of Crohn′s disease on transabdominal high-frequency ultrasound and contrast-enhanced ultrasound in Shanghai Tenth People′s Hospital from August 2011 to December 2012 were studied retrospectively. Contrast-specific imaging modes were performed and the ultrasound contrast agent was SonoVue. The thickness of inner, outer and all layers of intestinal walls in the lesion area were observed;the ratio between inner and outer bowel wall thickness was calculated;Limberg classiifcation was determined by Power-Doppler results. Likewise, contrast-enhanced ultrasound was used to evaluate the degree and area of bowel wall enhancement, as well as the changes over time. Variance analysis was applied to compare intestinal wall thickness, arrive time of contrast agent, time to peak and washing time of patients with Crohn′s disease from different Limberg groups, and further comparison between groups were anlysed with LSD-t test. Results The intestinal wall thickness of all 20 patients was larger than 4 mm, while the mean thickness of intestinal walls was (8.8±0.4) mm (range 5.5-12.0 mm);the ratio between inner and outer wall thickness was greater than 1.0. Limberg classiifcation wasⅡin 2 patients,Ⅲin 8 patients andⅣin 10 patients. There were two enhancement patterns shown on contrast-enhanced ultrasound:Pattern 1 in 13 (13/20, 65.0%) patients showing simultaneous enhancement in both inner and outer intestinal walls at the same time. Pattern 2 in 7 (7/20, 35.0%) patients showing outward enhancement from inner to outer wall with a predominance of inner wall. The wall thicknesses of patients with Crohn′s disease from Limberg Ⅱgroup, Limberg Ⅲgroup and Limberg Ⅳgroup were (6.6±0.1), (7.5±0.4) and (10.2±0.4) mm respectively. The thicknesses of inner bowel walls were (3.6±0.6), (5.0±0.2) and (7.3±0.3) mm respectively. CEUS time to peak was (30.5±2.1), (26.9±2.4) and (21.0±1.6) s respectively. The wash-in time of the contrast agent was (18.0±5.7), (10.6±1.0) and (8.7±1.2) s respectively. As the Limberg level increased, the thickness of the entire and inner bowel wall both increased, while CEUS time to peak and wash-in time of the contrast agent became longer. These difference was statistically significant. In addition, the ratio between inner and outter wall thickness also increased as the Limberg level increased, however, the difference was statistically insigniifcant. Likewise, the outer bowel wall thickness and the arrival time of the contrast agent in patients with Crohn′s diseases from different Limberg level groups showed no statistical significance. Conclusions The patients with active Crohn′s disease always showed thickened bowel walls, higher Limberg level and complete or partial enhancement of bowel wall on CEUS. There were some correlations between the above-mentioned ifndings.

The accuracy of puncture guided by intelligent positioning system using magnetic navigation / 中华医学超声杂志（电子版）

Objective To assess the accuracy of puncture guided by intelligent positioning (IP) system using magnetic navigation.Methods Five prepared targeted models at three certain depth (100 mm,large depth) underwent puncture guided by intelligent positioning system using IP and conventional ultrasound (US),respectively.Puncture errors,the number of attempt and spent time were recorded and compared .Results For the targets at small,medium and large depth,the errors of IP was (1.88 ±1.18),(1.56 ±0.56) and (3.99 ±1.10) cm,and the errors of conventional US was (4.52 ±2.23),(4.49 ±1.73) and (3.93 ±2.19) cm respectively.The errors of IP were significantly less than those of conventional US at small(t=-2.345,P=0.047) and medium(t=-3.608,P=0.007) depth,but there was no statistically significant difference at large depth (t=0.058,P=0.955). In the IP group,there were statistically significant differences for puncture errors between the small and large depth,as well as between medium and large depth ( F =8.923,P =0.010).There was no statistically significant difference for the errors of IP between the small and medium depth (t=-1.927,P=0.501).For the targets at small,medium and large depth,each puncture was performed in single attempt when guided by IP and in 2,1 and 2 attempt when guided by conventional US .At small and large depth,the numbers of attempt of IP were significantly less than those of conventional US (U=-2.372,P=0.018;U=-2.39, P=0.032).Whereas at medium depth,there was no significant difference (U=-1.000,P=0.690).For the targets at small,medium and large depth,each puncture spent (21.20 ±2.39)s, (27.00 ±4.00)s and (31.80 ±3.83)s when guided by IP,and(45.20 ±9.68),(26.80 ±4.21) and (54.60 ±13.48)s when guided by conventional US.The spent time of IP was less than that with conventional US for small and large depth targets(t =-5.383, P =0.001;t =-3.637, P =0.007).Whereas no statistically significant difference was found for the medium depth target (t=0.077,P=0.916).Conclusion In comparison with conventional US,IP system guided puncture is more accurate and the number of attempt and spent time is less .

Percutaneous ultrasound-guided thermal ablation for liver tumor with artificial pleural effusion or ascites / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Percutaneous ultrasound-guided thermal ablation is one of the major treatment methods for liver cancer. Tumor location close to the diaphragm or gastrointestinal tract was regarded as the treatment contraindication before due to poor visibility of the tumor or increased risk of thermal injury to the adjacent organs. This study used artificial pleural effusion or ascites to extend the indications of thermal ablation for liver cancer.</p><p><b>METHODS</b>Artificial pleural effusion (20 cases) or ascites (36 cases) was performed in 56 difficult cases of percutaneous thermal ablation for liver tumors. The technical success rates, the rate of approaching the procedure goal, complications, and local treatment response were assessed.</p><p><b>RESULTS</b>The technical success rates were 95% (19/20) for artificial pleural effusion and 100% (36/36) for artificial ascites, the achieve purpose rates were 100% (19/19) and 91.7% (33/36), the complete ablation rates were 84.2% (16/19) and 93.9% (31/33), respectively. Coughing, transient hematuria, and subcutaneous effusion were observed in 3 patients after the procedure of artificial pleural effusion, and hydrothorax in the right chest occurred in 1 patient during the artificial ascites process.</p><p><b>CONCLUSIONS</b>Thermal ablation with the use of artificial pleural effusion or ascites is a safe and effective treatment for liver tumors, and the technique can widen the indications of thermal ablation for liver tumors.</p>

Protective effects of nitric oxide donor on hydrogen peroxide-induced injury of cardiomyocytes / 生理学报

To investigate the protective effects of nitric oxide (NO) on cardiomyocytes against hydrogen peroxide (H2O2)-induced injury, cultured neonatal cardiomyocytes were divided into three groups: (1) normal group; (2) H2O2 group: cells were treated with H2O2 (0.1 mmol/L) for 4 h; (3) SNAP+ H2O2 group: cells were pretreated with NO donor S-nitroso-N-acetyl-1,1-penicillamine (SNAP, 0.5 mmol/L) 10 min before H2O2 treatment. Colorimetric assay was used to detect cell viability and lactate dehydrogenase (LDH) activity to evaluate cell injury. Apoptotic rate of cardiomyocytes were determined by flow cytometer. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) content were measured by colorimetric assay to evaluate cell antioxidant ability. Intracellular calcium was tested by laser confocal microscopy. The results showed that after treatment with H2O2, cell viability was significantly reduced to 58.3+/-7.6% compared with normal group (93.1+/-6.2 %). LDH activity and apoptotic rates were 1580.5+/-186.7 U/L and 26.4+/-5.7% respectively, significantly higher than that of normal group (631.4+/-75.6 U/L and 0). SNAP pretreatment markedly improved cell viability to 79.7+/-9.3% and reduced LDH activity and apoptotic rates to 957.8+/-110.9 U/L and 9.1+/-3.3%, respectively. Cells treated with H2O2 had a lower SOD activity of 14.73+/-1.68 NU/ml and a higher MDA content of (15.35+/-3.49) micromol/L compared with normal cells (19.67+/-0.85 NU/ml) and (6.95+/-0.83 micromol/L), respectively. Cells with SNAP pretreatment had a higher SOD activity of 21.36+/-3.11 NU/ml and a lower MDA content of 9.12+/-1.47 micromol/L compared with H2O2 group. Intracellular calcium content was reduced by SNAP administration while enhanced by H2O2. Pretreatment with SNAP could antagonize the effect of H2O2 of accelerating intracellular calcium content. Based on the results observed, it is concluded that NO donor SNAP may protect cardiomyocytes from being injured by H2O2. The underlying mechanisms may include improving cell antioxidant ability and reducing intracellular calcium overload.