Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection

Despite recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both, prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2 and retains activity against the variants of concern B.1.1.7 and B.1.351. Importantly, not only systemic but also intranasal application of DZIF-10c abolished presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies. Significance StatementMonoclonal neutralizing antibodies are important in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection. However, their intravenous application might lead to suboptimal bioavailability in the lung. We here precisely characterize a new monoclonal neutralizing antibody (DZIF-10c) that binds to the receptor binding domain of the spike protein of SARS-CoV-2. DZIF-10c neutralizes SARS-CoV-2 with exceptionally high potency and maintains activity against circulating variants of concern. The antibody has a favorable pharmacokinetic profile and protects mice from SARS-CoV-2 infection. Importantly, we show that intranasal administration of DZIF-10c generates protective efficacy. These results not only identify DZIF-10c as a novel highly potent neutralizing antibody, but further pave the way for a topical application of anti-SARS-CoV-2 antibodies.

Long-term follow-up result for the foam sclerotherapy in the treatment of lower extremity incompetent perforating veins / 中华普通外科杂志

Objective To evaluate the long-term follow-up results of foam sclerosing agent in the treatment ofincompetent perforating vein.Methods 153 cases (316 incompetent perforating veins)received the treatment of foam sclerotherapy.The closure of perforating branches was followed up by ultrasound.Results 12 cases (27 incompetent perforating veins) were lost to follow up.289 incompetent perforating veins got follow up,The median follow-up time was 17 months (11-36 months).Closure rate was 100％ in vessels less than 3 mm in diameter,while that was 76％ invessels with the diameter between 3-5 mm.Closure rate was 16％ in vessels larger than 5 mm in diameter.Conclusion The long-term efficacy of the foam sclerosing agent in the treatment of incompetent perforating vein depends on the diameter of the vein.

Perihematomal edema in basal ganglia intracerebral hemorrhage by using radiomics approach of CT images / 中华神经医学杂志

Objective To explore the value of CT images in distinguishing perihematomal edema in basal ganglia intracerebral hemorrhage with normal brain tissue,and its significance in assessing patients' conditions and prognoses.Methods CT images and clinical data of 120 patients with basal ganglia intracerebral hemorrhage admitted to our hospital from January 2017 to September 2018 were collected,and these 120 patients were randomly assigned to group of training data set (n=90) and group of test data set (n=30) at a ratio of 3∶l.The texture analysis software Mazda was used to preprocess the CT images and manually sketch the regions of interest (ROIs) to extract the texture parameters in patients from the group of training data set;Mazda software provides texture feature selection methods including mutual information (MI),Fisher coefficients (Fisher),classification error probability combined with average correlation coefficients (POE+ACC),and texture feature analysis including raw data analysis (RDA),principal component analysis (PCA),linear classification analysis (LDA) and nonlinear classification analysis (NDA);texture feature selection methods and texture feature analysis were grouped by pairs to establish different image omics labels;the error rate was used to evaluate the performance of different labels.Random forest model,support vector machine model and neural network model were built for texture parameters in patients from the group of test data set,and texture parameters extracted from patients from group of training data set were imported into these models;receiver operating characteristics curve was used to assess the performance of models.According to the maximum diameter of the hematomas,Glasgow coma scale (GCS) scores at admission,median of National Institute of Health Stroke Scale (NIHSS) scores 3 months after follow up,all patients were divided into two groups;Mazda software was used repeatedly for dimension reduction and establishment of different images omics labels;the sum of error rates from the two groups was taken as total error rate to evaluate the significance of different labels in predicting patients' conditions and prognoses.Results A total of 295 texture parameters were extracted from the ROIs of the best CT images of 90 patients from group of training data set,and 10 characteristic texture parameters were obtained by each of the three dimensionality reduction methods.Among all texture post-processing methods,the lowest error rate was 2.22％ for POE+ACC/NDA;AUCs were 0.87 (95％ CI:0.76-0.97),0.81 (95％ CI:0.72-0.93) and 0.76 (95％CI:0.67-0.89) for random forest model,support vector machine model and neural network model in the test dataset,respectively,which indicated that random forest model had the best forecast performance.The imaging omics labels established based on POE+ACC/NDA had the lowest total error rate for analysis of maximum diameter ofhematoma and GCS scores at admission (26.66％,23.33％);the imaging omics labels established based on Fishers coefficient method and NDA had the lowest total error rate(33.33％) for analysis of NIHSS scores at 3 months of follow up.Conclusion Radiomicmethod with proper model is of certain value in distinguishing erihematomal edema in basal ganglia intracerebral hemorrhage with normal brain tissue,and also has certain significance in evaluating the patienfs conditions and prognoses.

Thrombelastography in evaluating effect of antiplatelet drugs for patients undergoing peripheral endovascular treatment and relationship with ischemic-events-free duration / 中华普通外科杂志

Objective To evaluate the effect of antiplatelet drugs and ischemic-events-free duration by thromboelastography (TEG) in patients undergoing peripheral endovascular treatment.Methods From Mar 2015 to Oct 2016,38 patients undergoing initial successful peripheral stenting and then coming back for recurrent ischemic events.TEG was used to evaluate the platelet inhibition rate induced by arachidonic acid (AA％) approach,the platelet inhibition rate induced by adenosine diphosphate (ADP％) approach,and the ADP-induced platelet-fibrin clot strength (MAADP).Clinical feature differences between patients with MAADP ＞ 47 mm and MAADP ≤ 47 mm were compared.Results AA％ less than 50％ was found in 9 patients(23.9％),and ADP％ less than 30％ in 14 patients(36.8％).5 patients met the two conditions.Patients with MAADp ＞ 47 mm had a significantly lower ADP％ (x2 =10.755,P ＜ 0.001),compared to patients with MAADP ≤47 mm.Univariate survival analysis showed ADP％ ＜ 30％ and MAADP ＞47 mm were risk factors for getting shorter ischemic-events-free duration,compared to patients with ADP％ ≥ 30 (P ＜ 0.001),with MAADP ≤47 mm (x2 =4.408,P =0.036).Conclusions TEG may detect those patients who has a low response to antiplatelet drugs,and some TEG parameters may have a ischemic predictive value.

Endovascular treatment of abdominal aortic aneurysm and aortic bifurcation stenosis by unibody bifurcation stent graft / 浙江大学学报·医学版

OBJECTIVE@#To sum up experience in unibody bifurcation stent graft in the treatment of abdominal aortic aneurysm with aortic bifurcation stenosis.@*METHODS@#Clinical data of 19 cases of abdominal aortic aneurysm and aortic bifurcation stenosis received endovascular treatment using unibody bifurcation stent graft in Zhejiang Provincial People's Hospital during March 2009 and March 2018 were collected. The clinical characteristics, surgery procedure and follow-up results were reviewed.@*RESULTS@#Stent graft was successful in all patients, and the average operation time was (70.0±2.3) min. Leakage was found in 3 patients, in which 2 patients with type Ⅰ leakage and 1 patient with type Ⅱ leakage. All leakage disappeared 15 days after surgery. The 19 cases were followed-up for 9-48 months with the median follow-up time of 27 months, and no displacement, leakage and lower limb ischemia was observed.@*CONCLUSIONS@#Unibody bifurcation stent graft is of satisfactory long-term effect for patients with abdominal aortic aneurysm and aortic bifurcation stenosis, and can avoid displacement of stent graft after operation.

Ultrasound guided foam sclerosis for the treatment of lower extremity incompetent perforating veins / 中华普通外科杂志

Objective To discuss the curative effect and clinical significance of sclerosing foam agent in the treatment of chronic venous diseases (CVD) with incompetent perforating veins.Methods 65 cases of C4,C5,C6 CVD (a total of 84 limbs) underwent foam sclerotherapy closure for incompetent perforating vein.Patients were followed-up for 3 months,ultrasonography was used to observe the closure of perforating veins and the curative effect.Results 7 patients (9 limbs) were lost to follow-up,all with grade C4.In the 66 (C4,C5) limbs,pigmentation significantly subsided in 45,partial regression in 9,no change in 2.In the 9 limbs with grade C6,complete healing of ulcer in 5,partially healed in 3.Ultrasound observed satisfactory perforating vein closure.Conclusion Foam sclerotherapy closure for incompetent perforating vein has satisfactory effect,with good short-term curative result.

Effect of rosiglitazone on expression and excretion of connective tissue growth factor in renal tissue and urinary of diabetic rats / 中国药理学通报

Aim To study the effect of rosiglitazone(RGZ)on expression and excretion of connective tissue growth factor(CTGF) in renal tissue and urinary of diabetic nephropathy rats.Methods Three groups of rats were studied:normal control group(n=8),STZ-induced diabetic model group(n=8),diabetes RGZ-treatment group(n=8).Urinary CTGF was measured at the 1 st,4 th,6 th and 8 th week,as well as the expressions of CTGF protein(by histochemical staining)at the 8 th week by ELISA.Results The urinary excretion rates of CTGF at 4 th、6 th、8 th weeks and the expressions of CTGF protein in renal cortex at 8th weeks significantly increased in STZ-induced model group compared with those in normal group(P

Analyses of clinical results of treatment with gemcitabine and cisplatin for advanced hormone independent prostate cancer / 中国癌症杂志

Purpose:The aim of this study was to evaluate the clinical efficacy and toxicity of treatment with gemcitabine and cisplatin for hormone independent prostate cancer.Methods:18 cases of advanced hormone independent prostate cancers who received castration and antiandrogen medicines were confirmed to have multiple bone metastatic carcinomas by emission computed tomography(ECT), and hepatic , adrenal and intracranial metastasis were found respectively each in 1 patient, and the value of PSA(prostatic special antigen) had on ascending trend in all patients. Gemcitabine 1000 mg/m~(2) +NS 100 ml was administered by intravenous drip on days 1,8 and cisplatin 100 mg/m~(2) +NS 500 ml was administered by intravenous drip on day 1 or cisplatin 30 mg/m~(2) +NS 250 ml was administered by intravenous drip on days 1 to 5 in each 28-day cycle.Results:Levels of PSA descent to normal titer(