Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants

Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

Microbubble-enhanced non-focused ultrasound treatment of posttraumatic liver hemorrhage / 中华创伤杂志

Objective To investigate the effect of microbubble-enhanced non-focused ultrasound on posttraumatic liver hemorrhage.Methods Twenty healthy New Zealand white rabbits with posttraumatic liver hemorrhage were divided into control group,microbubble group,ultrasound with microbubble group,and heparin with ultrasound and microbubble group according to the random number table,with five rabbits per group.Thrombin time (TT),prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (FIB),and coagulation reaction time (R value) and mechanical strength (A value) of the thrombelastogram were detected.Pre-and post-treatment bleeding were measured to evaluate the hemostatic effect.Liver specimens were harvested to perform histopathological study with HE staining.Results TT [(25.8 ± 11.3) s] and APTF [(58.7 ± 18.7) s] in heparin with ultrasound and microbubble group showed significant prolongation compared with other three groups (P ＜ 0.05).Control group showed higher FIB than other three groups,but the differences were insignificant (P＞0.05).PT did not differ significantly among groups (P＞0.05).R value [(78.3±5.1) min] and A value [(0.13 ± 0.05)mm] in heparin with ultrasound and microbubble group differed significantly from these in other three groups (P0.05 ).After treatment,bleeding area in heparin with ultrasound and microbubble group [(2.2 ±1.3)cm2] wasincreased when compared to ultrasound with microbubble group[(0.8+0.7) cm2](p< 0.05 ), butboth were lower than that in control group [( 5.7+0.6)cm2 ]and microbubble group [( 5.3 ±0.6)cm2]( P<0.05). HE staining showed significant hepatic cell edema in ultrasound with microbubble groupand heparin with ultrasound and microbubble group that compressed hepatic sinus,blood vessels in theportal area and central vein,and significant blood stasis in blood vessels.Conclusion Microbubblesenhanced non-focused ultrasound has good hemostatic effect for posttraumatic liver hemorrhage.

Logistic Regression Analysis on Risk Factors of Northwest Dryness Syndrome Among Patients of Metabolic Syndrome in Xinjiang Uygur Autonomous Region / 中国中医药信息杂志

Objective To analyze risk factors of northwest dryness syndrome (NDS) among the patients of metabolic syndrome in Xinjiang Uygur Autonomous Region.Methods Totally 321 cases of metabolic syndrome in Kashgar, Hami and Urumqi were collected to filter 15 variables to calculate OR value and 95% CI, and evaluated by single factor and multi-factor analysis by applying conditional Logistic regression analysis.Results Single factor conditional Logistic regression analysis showed that high fat diet, addiction to hot diet, salty diet, smoking history and hypertension were the risk factors of NDS. The OR values of them were 0.387, 0.071, 0.033, 2.614 and 0.440, respectively (P<0.05). Multi-factor conditional Logistic regression analysis showed that smoking history, alcohol drinking history, high fat diet and hypertension were all entered into regression model. The OR values of them were 3.945, 4.334, 0.370 and 2.142, respectively (P<0.01).Conclusion Patients of metabolic syndrome with a high fat, salty and hot diet are suggested to adjust their diet habit by adding sour food, giving up smoking and drinking, and controlling their blood pressure. It will be helpful for them to adapt local climate and living environment, and reduce the attack rate of NDS.