Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom

In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on individuals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected individual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea - also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger sample of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.

MALAT1 induces osteosarcoma progression by targeting miR-206/CDK9 axis.

Long noncoding RNAs (LncRNAs) have been reported to participate in cancer development, including osteosarcoma. Here, in our study, we observed that lncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) was remarkably overexpressed in osteosarcoma. However, the role it plays in osteosarcoma proliferation mediated by miR-206/cyclin-dependent kinase 9 (CDK9) axis remains uninvestigated. It was found that miR-206 was decreased and CDK9 was elevated in human osteosarcoma cells including MG63, Saos-2, U2OS, and KHOS compared with human osteoblast cell line hFOB 1.19. In addition, it was exhibited that knockdown of MALAT1 was able to inhibit osteosarcoma cell proliferation, which suggested that MALAT1 played an oncogenic role in osteosarcoma development. Bioinformatics analysis indicated that MALAT1 can function as a competing endogenous RNA by sponging miR-206. Because miR-206 has been identified as a significant tumor suppressive gene in multiple cancers, we validated that mimics of miR-206 can restrain osteosarcoma progression. Furthermore, dual-luciferase reporter assay, RNA binding protein immunoprecipitation, and RNA pull-down assay demonstrated the correlation between miR-206 and MALAT1. Besides these, CDK9 was predicted as a downstream gene of miR-206, and we observed that MALAT1 can regulate osteosarcoma progress by modulating CDK9 expression via sponging miR-206. In conclusion, our study implied that MALAT1/miR-206/CDK9 axis can provide novel insights into the biological mechanism of osteosarcoma progression.

A voxel-based diffusion kurtosis imaging study of whole-brain in alcohol dependent patients / 中华放射学杂志

Objective To study the changes of micro structure of white matter and gray matter in alcohol dependent patients by using diffusion kurtosis imaging(DKI) based on the method of voxel-based analysis.Methods Thirty alcohol dependent individuals and twenty healthy control volunteers,matched in gender, age, handedness and education, were enrolled as the alcohol dependent group and control group from September 2016 to June 2017.Michigan alcoholism screening test(MAST)was done for all subjects.All the subjects underwent DKI data acquisition by MR scanning. The relevant parameters were obtained by DKE software, including fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity(AD), radial diffusivity(RD), mean kurtosis(MK), axial kurtosis(AK), radial kurtosis(RK), FA of kurtosis(FAK). Independent sample t test was performed to evaluate the significant difference of DKI parameters of two groups,meanwhile,the correlation analysis was conducted in DKI parameter values of different brain regions and MAST scores. Results Compared with the healthy control group, the FA value, MK value and RK value were decreased while the RD value was increased in alcohol dependence group, and there was significant difference between the two groups respectively(P<0.001). There was no significant difference between the two groups in the other parameters (AD, MD, AK, FAK). Compared with the healthy control group,the FA values of left lingual gyrus(164 voxels,t=-5.582)and left hippocampus(38 voxels,t=-3.664) increased;the MK value of left cerebellum posterior lobe(71 voxels,t=-4.004)reduced;the RK value of left cerebellum posterior lobe(67 voxels, t=-4.174), left middle cingulum(32 voxels, t=-3.925), left superior parietal gyrus(36 voxels,t=-3.812)reduced;and the RD value of the left inferior parietal gyrus(31 voxels,t=3.731)increased in alcohol dependence group.There was no correlation between MAST score and the value of DKI parameters. Conclusions There are dominant areas of brain injury in patients with alcohol dependence. The DKI parameters can reflect the changes of the whole brain microstructure of alcohol dependent patients and provide imaging basis in the diagnosis of alcohol dependence.

Stenting of iliac vein obstruction following catheter-directed thrombolysis in lower extremity deep vein thrombosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Catheter-directed thrombolysis (CDT) for deep venous thrombosis (DVT) of the lower extremity has good effect, but whether iliac vein stent placement after thrombolytic therapy is still controversial. The goal of this study was to evaluate the efficacy of stent placement in the iliac vein following CDT in lower extremity DVT.</p><p><b>METHODS</b>This was a single-center, prospective, randomized controlled clinical trial. After receiving CDT, the major branch of the distal iliac vein was completely patent in 155 patients with lower extremity DVT, and 74 of these patients with iliac vein residual stenosis of >50% were randomly divided into a control group (n = 29) and a test group (n = 45). In the test group, stents were implanted in the iliac vein, whereas no stents were implanted in the control group. We evaluated the clinical indicators, including patency of the deep vein, C in CEAP classification, Venous Clinical Severity Score (VCSS), and Chronic Venous Insufficiency Questionnaire (CIVIQ) Score.</p><p><b>RESULTS</b>All patients had postoperative follow-up visits for a period of 6-24 months. Venography or color ultrasound was conducted in subjects. There was a significant difference between the patency rate at the last follow-up visit (87.5% vs. 29.6%) and the 1-year patency rate (86.0% vs. 54.8%) between the test and control groups. The change in the C in CEAP classification pre- and post-procedure was significantly different between the test and control groups (1.61 ± 0.21 vs. 0.69 ± 0.23). In addition, at the last follow-up visit, VCSS and CIVIQ Score were both significantly different between the test and control groups (7.57 ± 0.27 vs. 0.69 ± 0.23; 22.67 ± 3.01 vs. 39.34 ± 6.66, respectively).</p><p><b>CONCLUSION</b>The stenting of iliac vein obstruction following CDT in lower extremity DVT may increase the patency of the deep vein, and thus provides better efficacy and quality of life.</p>

Analysis of cause and treatment of acute limb ischemia complicated in peripheral endovascular interventions / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the cause and treatment of acute limb ischemia in endovascular therapy of the lower extremity arterial occlusive disease.</p><p><b>METHODS</b>Clinical data of 54 cases of acute limb ischemia in the endovascular treatment of 685 cases of lower extremity arterial occlusive disease from June 2003 to April 2012 was analyzed retrospectively. There were 43 male and 11 female patients, with a mean age of 72.3 years (ranging from 56 to 82 years). The major causes which resulted in acute limb ischemia included: arterial embolization of 43 cases, arterial thrombosis of 8 cases, arterial dissection of 3 cases. The acute limb ischemia occurred in the process of balloon angioplasty/stent in 36 cases, catheter-directed thrombolysis in 17 cases, Silverhawk atherectomy in 1 cases. Thirty-two cases were treated by endovascular treatment, 9 cases by surgical procedures (bypass or embolectomy), 13 cases by the combination of endovascular therapy and surgical procedures.</p><p><b>RESULTS</b>Treatment were successfully accomplished in 50 of 54 cases, and failed in 4 cases which had surgical amputation. There were no deaths in all the patients. Forty-five of 54 cases were followed up for the average of 40.3 months. Six cases had ischemic symptoms recurrence in 43 artery embolization patients, in whom 4 cases were cured by endovascular treatment, 2 cases were cured by toe amputation. One case of bypass anastomotic stenosis and one case of stent restenosis were successfully cured by endovascular treatment in 8 arterial thrombosis patients. One cases of below-knee artery stent occlusion in 3 arterial dissection patients was cured by medical treatment. Four cases of amputation patients were followed up in good condition.</p><p><b>CONCLUSIONS</b>Most patients of acute limb ischemia complicated in endovascular therapy could be treated by endovascular therapy. Surgical procedures in time is still the best choice for the patients in whom the endovascular therapy was not satisfied.</p>

Endovascular treatment of iliac vein compression syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Iliac vein compression syndrome (IVCS), the symptomatic compression of the left common iliac vein between the right common iliac artery and the vertebrae, is not an uncommon condition. The aim of this research was to retrospectively evaluate long-term outcome and the significance of endovascular treatment in patients with left IVCS.</p><p><b>METHODS</b>Between January 1997 and September 2008, 296 patients received interventional therapy in the left common iliac vein. In the second stage, 170 cases underwent saphenous vein high ligation and stripping. Two hundred and thirty-one cases were followed up over a period of 6 to 120 months (average 46 months) and evaluated for symptom improvement with color ultrasound and ascending venography.</p><p><b>RESULTS</b>The stenotic or occlusive segments of the left iliac vein were successfully dilated in 285 cases, of whom 272 received stent implantation therapy. Most of the patients achieved satisfactory results on discharge. During the follow-up period, varicose veins were alleviated in 98.7% of the patients, and leg swelling disappeared or was obviously relieved in 84% of cases. About 85% of leg ulcers completely healed. The total patency rate was 91.7% as evaluated with color ultrasound and 91.5% with ascending venography.</p><p><b>CONCLUSIONS</b>Endovascular treatment of IVCS provides effective symptomatic improvement and good long-term patency in most patients.</p>

Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats.</p><p><b>METHODS</b>Forty-eight male SD rats were randomly assigned into six groups (n = 8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n = 8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R.</p><p><b>RESULTS</b>The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12 - 24 hours after ischemia reperfusion.</p><p><b>CONCLUSION</b>COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12 - 24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.</p>

Radical correction of Budd-Chiari syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interventional therapy is widely accepted as the first choice for the treatment of the Budd-Chiari syndrome, but the use of radical correctional therapy should not be discarded. This study describes radical correction by controlling bleeding from distal end of pathological segment of the inferior vena cava (IVC) and discusses potential surgical errors and postoperative complications.</p><p><b>METHODS</b>Of the 216 patients in the study, 78 were treated with simple membranectomy, 64 with dissection of the pathological segment of the IVC and vascular prosthesis or pericardial patch plasty, 60 with resection of the pathological segment of the IVC and orthotopic graft transplantation with vascular prosthesis, and 14 with resection of the occlusive main hepatic vein and its upper IVC, hepatic venous outflow plasty and vascular prosthesis orthotopic graft transplantation from the hepatic venous entrance to the IVC of right atrial ostium.</p><p><b>RESULTS</b>Except 14 cases who were discharged after hepatic vein outflow plasty, four cases died postoperatively, and 198 patients were discharged without complications. The symptoms of 15 patients were relieved partially and 2 without any change. There were no deaths intraoperatively. Of the 112 cases who were followed up for 72 months, 13 suffered from a relapse.</p><p><b>CONCLUSIONS</b>Radical correction is a beneficial therapy in the treatment of Budd-Chiari syndrome.</p>

Effect of puerarin on neural function and histopathological damages after transient spinal cord ischemia in rabbits / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits.</p><p><b>METHODS</b>Thirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L5) were removed immediately for histopathological study.</p><p><b>RESULTS</b>The neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P<0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P<0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r=0.839, P<0.01).</p><p><b>CONCLUSIONS</b>Puerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.</p>