Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody

The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2x259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus clades. S2x259 broadly neutralizes spike-mediated entry of SARS-CoV-2 including the B.1.1.7, B.1.351, P.1 and B.1.427/B.1.429 VOC, as well as a wide spectrum of human and zoonotic sarbecoviruses through inhibition of ACE2 binding to the RBD. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2x259 possesses a remarkably high barrier to the emergence of resistance mutants. We show that prophylactic administration of S2x259 protects Syrian hamsters against challenges with the prototypic SARS-CoV-2 and the B.1.351 variant, suggesting this mAb is a promising candidate for the prevention and treatment of emergent VOC and zoonotic infections. Our data unveil a key antigenic site targeted by broadly-neutralizing antibodies and will guide the design of pan-sarbecovirus vaccines.

Unexpected Detection of Spontaneous Isolated Superior Mesenteric Artery Dissection by Renal Artery CT Imaging in 12 Hypertension Patients / 中国循环杂志

Objective: To study the features of spontaneous isolated superior mesenteric artery dissection (SISMAD) by unexpected detection of renal artery dual-source CT (DSCT) imaging in hypertension patients. Methods: A total of 4107 patients with suspected secondary hypertension received renal artery DSCT examination in our hospital from 2010-03 to 2015-04 were studied and SISMAD was unexpectedly found in 12 patients. There were 3 patients with mild abdominal pain and the rest without obvious abdominal symptoms. The position and length, true and false lumens, detached tunica intimal flap and branch involvement of dissection, intestinal wall edema and ileus were recorded. Results: SISMAD in all 12 (0.3%) patients were found unexpectedly. Axial CT with post-processing technique clearly displayed the ruptured tunica intimal orifice, true and false lumens, detached intimal flap; the branches were all originated from true lumen. According to Sakamoto classification, all 12 patients were belong to Type I as the true and false lumens were with an entry and re-entry respectively, no filling defect in false lumen. The distance from orifice of dissection to root of abdominal aorta was (26.7 ± 11.3) mm and the length of dissection was (35.1 ± 11.7) mm.There were 10 patients with aneurysmal expansion with the diameter of (11.9 ± 2.5) mm. Conclusion: Unexpected detection of SISMAD by renal artery CT imaging was about 0.3%, radiologist should pay special attention to find superior mesenteric artery dissection in hypertension patients.

Effect of autologous hematopoietic stem cell transplantation on serum trace elements and lactate dehydrogenase activity in patients with malignant lymphoma / 中国生化药物杂志

Objective To investigate effect of autologous hematopoietic stem cell transplantation on serum trace elements and lactate dehydrogenase activity in patients with malignant lymphoma.Methods 80 patients with malignant lymphoma collected in our hospital from May 2013 to May 2014,40 cases in each group, Hodgkin lymphoma ( HL) patients were treated with ABVD ( doxorubicin, bleomycin, vincristine, dacarbazine) regimen of chemotherapy; Non-Hodgkin,s lymphoma ( NHL) patients were treated with standard CHOP ( cyclophosphamide, vincristine, epirubicin, dexamethasone) regimen of chemotherapy of two group.Chemotherapy drugs combined with granulocyte colony stimulating factor ( G-CSF) was used to mobilize APBSC.Application of 10μg/(kg? d)G-CSF 5 in bone marrow suppression after chemotherapy, detected white cell increased 3.0 ×109/L , platelets rose to 50 ×109/L, collected APBSC,The frozen stock solution of cell was joined and frozen.24 h after pre-treatment, the frozen peripheral blood hematopoietic stem cells of the subclavian vein was transfused for patients in experimental group.Control group continued to receive chemotherapy. After treatment, the Cu level, Zn level and lactate dehydrogenase activity were detected in all patients.ResuIts After treatment, Zn levels of two groups increased (P<0.05), Cu and Cu/Zn levels decreased (P<0.05).Compared with control group, the level of Zn was higher in experimental group (P<0.05), and the level of Cu and Cu/Zn was lower (P<0.05).After treatment, the lactate dehydrogenase activity of two groups decreased (P<0.05), and experimental group was more lower than control groupy (P<0.05).ConcIusion Autologous hematopoietic stem cell transplantation can significantly reduce the level of Cu in patients with malignant lymphoma , elevate Zn level and decrease the activity of lactate dehydrogenase, which has guiding significance for clinical.

Value of multi-slice CT angiography in detection of carotid artery stenosis / 中国医师进修杂志

Objective To evaluate the accuracy of multi-slice CT(MSCT) angiography in detection of carotid artery stenosis. Methods A total of 29 consecutive patients with known or suspected carotid artery disease were studied by MSCT. The results were compared with quantitative carotid angiography.Results In the 203 carotid arteries of 29 patients, 22 of 24 carotid arteries with significant stenosis ( ≥ 30% reduction of vessel diameter) were correctly detected by MSCT,and 171 of 179 carotid arteries with normal or mild stenosis ( ＜ 30% reduction of vessel diameter) were correctly detected by MS CT. These values corresponded to sensitivity of 91.7% (22/24), specificity of 95.5% (171/179), positivè predictive value of 73.3% (22/30), and negative predictive value of 98.8% ( 171/173 ) for the detection of significant carotid artery stenosis by MSCT. In the 203 carotid arteries of 29 patients, 14 of 14 carotid arteries with high-grade stenosis were correctly detected by MSCT,and 186 of 189 carotid arteries with normal or mild stenosis were correctly detected by MSCT. These values corresponded to sensitivity of 100.0%(14/14), specificity of 98.4% (186/189), positive predictive value of 82.4% (14/17),and negative predictive value of 100.0%(186/186) for the detection of high-grade carotid arteries stenosis by MSCT. Conclusions MSCT angiography shows significant carotid artery stenosis with high accuracy. It may be used as an alternative for carotid angiography in detection of carotid artery stenosis.

Analysis of Left Atrial Appendage by Multislice Computed Tomography in Patients With and Without Paroxysmal Atrial Fibrillation / 中国循环杂志

0.05]. Conclusion:Besides the enlargement of LA,the volume of LAA and the area of LAA ostium were significantly increased in AF patients.Preprocedural assessment of LAA ostium should be helpful for the selection of occlusion devices.Because LAA is be very close to LCX,the selection of AF ablation strategies should be carefully taken to avoid possible damage of LCX.