Objective To observe the value of a YOLOX target detection model for automatically identifying endovascular interventional instruments on images of digital subtract angiography(DSA).Methods DSA data of 37 patients who underwent abdominal endovascular interventional therapy were retrospectively analyzed.Totally 4 435 DSA images were captured and taken as data set,which were divided into training set(n=3 991)and verification set(n=444)at the ratio of 9∶1.Six kinds of endovascular interventional instruments were labeled.YOLOX algorithm was applied for deep learning of data in training set in order to build a target detection model,and the efficacy of the model for automatically identifying endovascular interventional instruments on DSA images was evaluated based on varification set.Results A total of 6 668 labels were put on 4 435 DSA images,aimed on Terumo 0.035in loach guide wire(n=587),Cook Lunderquist super hard guide wire(n=990),Optimed 5F with graduated pig tail catheter(n=1 680),Cordis MPA multi-functional catheter(n=667),Boston Scientific V-18 controllable guide wire(n=1 330)and Terumo 6F long sheath(n= 1 414),respectively.The training set contained 527,875,1 466,598,1 185 and 1 282,while the verification set contained 60,115,214,69,145 and 132 the above labels,respectively.The pixel accuracy of YOLOX target detection model for automatically identifying the above instruments in the verification set was 95.23%,97.32%,99.18%,98.97%,97.60%and 98.19%,respectively,with a mean pixel accuracy of 97.75%.Conclusion YOLOX target detection model could automatically identify endovascular interventional instruments on images of DSA.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

Objective:To explore different strategies of central repair first or malperfusion first to treat type A aortic dissection complicated with limb malperfusion.Methods:From January 2020 to December 2021, 302 patients were diagnosed with acute type A aortic dissection, and 17 consecutive patients were diagnosed as type A acute aortic dissection complicated with limb malperfusion and underwent Sun’s procedure. There were 16 males and 1 female with an average of(52.6±4.2)years. Surgical strategies were as follows: immediate central repair-Sun’s procedure in 14 patients, endovascular stenting followed by central repair in 3 patients, endovascular stenting after central repair in 1 patient.Results:The incidence rate of limb malperfusion of acute Stanford A aortic dissection was 5.6%(17/302). Average extracorporeal circulation time was(271.8±38.9)min, average aortic cross-clamp time was (186.3±31.8)min, and the average circulatory arrest time was (48.75±11.3)min. Early mortality rate was 17.6%(3/17). Two patients were left hospital voluntarily because of cerebral infarction. One patient underwent leg incision osteofascial compartment syndrome and discharged unevently. Five patients underwent continuous renal replacement therapy and hemoperfusion. Follow-up results showed that patients with serious limb malperfusion have symptoms of nerve dysfunction including amyosthenia and sensory disturbance, but recovered gradually with rehabilitation.Conclusion:Sun’s procedure is safe and feasible for type A acute aortic dissection complicated with mild limb malperfusion. For serious limb malperfusion, endovascular stent followed by Sun’s procedure is a good choice with CRRT and hemoperfusion.

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To evaluate the effects of Xiongzhi Dilong decoction(XZDLD)and its wind medicine on calcitonin gene-related peptide(CGRP)-induced migraine and explore the mechanism through the CGRP/inducible nitric oxide synthase(iNOS)pathway.Methods:Rats were divided into control,model,XZDLD,XZDLD(external wind),XZDLD(internal wind),and olcegepant groups.CGRP was injected into the dura mater to induce a migraine.The frequency of head scratching,cage climbing,and facial grooming was observed.The pain threshold,the levels of CGRP,pituitary adenylate cyclase activating polypeptide(PACAP),substance P(SP),and the plasma protein extravasation(PPE)ratio were measured.The phosphorylation levels of p38,extracellular signal-regulated kinase 1/2(ERK1/2),and expression of iNOS were detected by western blot.Results:Compared with the model group,the three modified XZDLD groups showed reduced frequency of head scratching and cage climbing in the first 30 min(all P＜.05).Facial grooming frequency was reduced in XZDLD and XZDLD(external wind)groups(P=.0003 and P=.0131,respectively).External wind medicine played a more important role in increasing mechanical pain threshold than internal wind medicine.Moreover,compared with the model group,the three modified XZDLD groups demonstrated reduced plasma levels of CGRP and PACAP(all P＜.05).No difference in the SP level was observed among the six groups.XZDLD reduced PPE ratio.XZDLD and XZDLD(external wind)groups suppressed the CGRP/iNOS pathway by inhibiting the p-p38/p38 ratio and the expression of iNOS.No difference in pERK1/2/ERK1/2 ratio was detected among the six groups.Conclusion:XZDLD increases pain threshold,downregulates the expression of CGRP and PACAP,and reduces PPE ratio by inhibiting the CGRP/iNOS pathway.External wind medicine is more effective than internal one on improving facial grooming and head scratching,increasing the mechanical pain threshold,and inhibiting the expression of iNOS.

Amino Acid Sequence ; Coronavirus/drug effects* ; Coronavirus Infections/drug therapy* ; Drug Design ; Humans ; Protein Structure, Secondary ; Spike Glycoprotein, Coronavirus/metabolism* ; Viral Fusion Protein Inhibitors/pharmacology* ; Viral Fusion Proteins/metabolism*

Objective:To systematically analyze the clinical features of severe fever with thrombocytopenia syndrome (SFTS) and to provide evidence for the prevention and treatment of SFTS.Methods:Relevant studies of SFTS from six databases, including China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, PubMed, Cochrane Library and Embase from January 2009 to May 2019 were systematically searched and identified. The literatures were screened and the data of patients′ epidemiology, clinical manifestations, laboratory examinations and prognosis were obtained. Revman 5.2 software was used for meta analysis.Results:Sixty-eight Chinese literatures and fourteen English literatures encompassing 6 780 patients with SFTS were included in the final analysis. Of these patients, 845 cases (12.46%) died. SFTS mostly occurred in mountainous and hilly areas, and farmers (3 637 cases) were the usual victims. The onset season was mostly in summer and the peak was from May to August each year. There were 1 434 patients had a clear history of tick bites, and 21 cases were human-to-human transmitted.There were 6 071 cases (89.54%) presented with fever, 5 407 cases (79.75%) presented with fatigue, 3 140 cases (46.31%) presented with muscle soreness, and 2 300 cases (33.92%) presented with chills.Using random effects model for meta analysis, the levels of creatine kinase (CK) (mean difference ( MD)=500.40, 95% confidence interval ( CI) 380.51-620.28, P<0.01) and lactic acid dehydrogenase (LDH)( MD=442.81, 95% CI 152.85-732.78, P=0.003) in severe patients were both higher than those in mild patients, and the difference were both statistically significant. The risk of death increased in patients aged>60 years( MD=8.19, 95% CI 4.03-12.36, P<0.01). The levels of CK( MD=530.92, 95% CI 29.27-1 032.56, P=0.040), LDH( MD=609.28, 95% CI 80.25-1 138.31, P=0.020), urea nitrogen ( MD=4.67, 95% CI 3.05-6.30, P<0.01) and creatinine ( MD=43.05, 95% CI 23.49-62.62, P<0.01) of patients in the death group were all higher than those in the survival group. The differences were all statistically significant. Conclusions:During the course of SFTS, the patients may show impaired blood system, heart, liver and kidney functions with high mortality. Clinicians should timely monitor the changes of blood routine, myocardial enzyme spectrum, liver and kidney functions and other indicators, so as to find cardiovascular and other system complications as early as possible. Timely treatment could not only reduce liver, heart and other organ injuries, but also reduce mortality.

Objective: To analyze the prevalence of severe fever with thrombocytopenia syndrome virus(SFTSV)infection in Zhoushan island of Zhejiang province and the duration of serum positive IgG antibody in patients infected with SFTSV. Methods: One thousand one hundred and twenty-two healthy people from Zhoushan island of Zhejiang province were recruited for cross-sectional study in August 2019, including 641 from non-epidemic areas and 481 from epidemic areas. The serum SFTSV-IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA), and the positive rates of SFTSV-IgG antibody were compared between people from the epidemic areas and non epidemic areas. Meanwhile, the antibody titer of SFTSV-IgG in 19 patients confirmed between July 2011 and June 2018 was detected by indirect ELISA. SPSS 17.0 software was used to analyze data. Results: The positive rate of SFTSV-IgG antibody was 1.5% (7/481) in the epidemic area, which was higher than that in the non-epidemic area (0/641) (χ²=7.187, P<0.01). The positive rates of SFTSV-IgG antibody in 2019 were lower than those in the epidemic area (11.7%) and non-epidemic area (2.5%) in 2013 (χ²=22.556 and 10.352, both P<0.01). The serum SFTSV-IgG antibody of 18 patients with previous infection was still positive, and the longest one lasted for 8 years. Conclusions There is a SFTSV latent infection in population from epidemic area of Zhoushan island. The SFTSV-IgG antibody can last for a long time in patients with SFTS and it may have certain protective effect.

A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
AIDS Vaccines ; chemistry ; immunology ; Antibodies, Neutralizing ; immunology ; HIV Antibodies ; immunology ; HIV Envelope Protein gp41 ; immunology ; HIV-1 ; chemistry ; immunology ; Humans