Objective To explore the association of the magnitude of systolic blood pressure reduction(SBPr)with post-procedure 24 h symptomatic intracranial hemorrhage(sICH)and 90-day clinical outcomes in patients with successful endovascular thrombectomy(EVT).Methods Consecutively registered patients with EVT caused by anterior circulation large vessel occlusion stroke(LVOS)in the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital)between July 2015 and April 2023 and patients with successful reperfusion were analyzed.Demographic data,medical history(hypertension,diabetes),the trial of Org 10172 in acute stroke treatment(TOAST)classification,the baseline National Institutes of Health Stroke Scale(NIHSS)score and the baseline Alberta stroke early CT(ASPECT)score of patients were collected.And procedure related parameters(including time from onset to puncture,time from onset to reperfusion,occluded site[internal carotid artery,M1 segment of middle cerebral artery,M2 segment of middle cerebral artery],collateral circulation status[determined based on preoperative occluded angiography showing the range of collateral circulation in the occluded vessel area,defined as good collateral circulation with a reflux range of ≥ 50％and poor collateral circulation with a reflux range of＜50％]),immediate postoperative reperfusion status(evaluated using the modified thrombolysis for cerebral infarction[mTICI]grading,successful reperfusion defined as mTICI grading of 2b-3),24 hours sICH,and 90 days clinical outcomes(evaluated using the modified Rankin scale score at 90days after EVT,with a score ≤ 2indicating a good prognosis and a score＞2indicating a poor prognosis).SBPr was defined as(baseline SBP-mean SBP)/baseline SBP x 100％.According to the the magnitude of SBPr,SBPr is divided into 5 categories(＜-10％,-10％-10％,＞10％-20％,＞20％-30％and＞30％).Based on the clinical outcomes at 90 days and the occurrence of sICH at 24 hours after EVT,patients were divided into a good prognosis group and a poor prognosis group,as well as an sICH group and a non-sICH group.The relationship between SBPr and postoperative 90 days clinical prognosis or sICH was analyzed using a binary Logistic regression model.Subgroup analysis was conducted based on a history of hypertension(yes and no),continuous intravenous hypotensive therapy(yes and no),baseline ASPECT scores(3-5 and 6-10),and collateral circulation status(good and bad).Using a restricted cubic plot to depict the relationship between SBPr and sICH and clinical prognosis at 90days.Results(1)In total,731 patients were included.The median age was 71(62,77)years and 424(58.0％)were men.The median baseline NIHSS score was 14(12,18),the median baseline ASPECT was 9(7,10),405(55.4％)patients achieved 90-day modified Rankin scale score 0-2,and 35 patients(4.8％)developed sICH.(2)Multivariate analysis showed that the older age(OR,1.036,95％CI 1.017-1.056),the higher baseline NIHSS score(OR,1.095,95％CI1.049-1.144),the lower baseline ASPECT score(OR,0.704,95％CI 0.636-0.780),diabetes(OR,1.729,95％CI 1.084-2.758),bad collateral circulation(good collateral circulation vs.bad collateral circulation,OR,0.481,95％CI 0.332-0.696)and SBPr＞30％(SBPr-10％-10％as a reference,OR,2.238,95％CI 1.230-4.071),the higher the risk of poor clinical outcomes at 90 days(all P＜0.05).Continuous intravenous hypotensive therapy is a risk factor for postoperative 24 h sICH(OR,2.278,95％CI 1.047-4.953;P=0.038),while SBPr 20％-30％is associated with a lower risk of postoperative 24 h sICH(SBPr-10％-10％as a reference,OR,0.362,95％CI0.131-0.998;P=0.049).(3)The restrictive cube plot shows that there is a U-shaped relationship between SBPr after EVT and poor clinical outcomes at 90 days,while there is a nearly linear relationship with the occurrence of sICH.The more SBP reduction,the lower the incidence of sICH.(4)In the subgroup analyses,in the non-hypertension history and the good collateral circulation group,SBPr＞30％has a higher risk of poor clinical outcomes compared to SBPr-10％-10％(OR and 95％CI were 2.921[1.000-8.528]and 2.363[1.078-5.183],respectively,with P=0.05 or P＜0.05);After EVT,the group receiving continuous intravenous hypotensive therapy and the baseline ASPECT score 6-10 groups showed a significant correlation between SBPr＞30％and poor clinical outcomes at 90 days(SBPr-10％-10％as a reference,OR and 95％CI were 2.646[1.168-5.993]and 2.481[1.360-4.527],respectively,with P＜0.05).The correlation between SBPr and lower incidence of sICH was only found in the subgroup of poor collateral circulation(SBPr-10％-10％as a reference,SBPr＞20％-30％:OR,0.133,95％CI 0.027-0.652;SBPr＞30％:OR,0.104,95％CI 0.013-0.864;all P＜0.05).Conclusions Among patients who achieved successful reperfusion with EVT,SBPr might be related to a worse functional outcome at 90 days and sICH 24 h after operation.However,the relationship may exhibit significant heterogeneity across different subgroups.Baseline ASPECT score,history of hypertension,collateral circulation,and the use of continuous venous hypertension after EVT have been highlighted in individualized blood pressure management after EVT.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To establish an in vivo infection model of H5N1 pseudovirus and to detect the neutralizing activity of FHA3 antibody using this model. Methods:Based on the sequence information of hemagglutinin (HA) and neuraminidase (NA) of A/Anhui/1/2005/H5N1 strain, two recombinant plasmids of pcDNA3.1-HA5 and pcDNA3.1-NA1 were constructed. The two plasmids and plasmid pNL4-3.Luc.R-E- were co-transfected into 293T cells to prepare H5N1 pseudovirus supernatant. The morphology of pseudovirus particles in the supernatant was observed by electron microscopy. MDCK cells were infected with the pseudovirus supernatant and the virus titer was detected. BALB/c mice were injected with the pseudovirus supernatant by intraperitoneal injection and subjected to bioluminescence imaging at 2, 5, 8, and 12 d after infection to detect the pseudovirus infection in vivo. The functional activity of FHA3 antibody in vivo was evaluated using the established mouse infection model. Results:The recombinant plasmids pcDNA3.1-HA5 and pcDNA3.1-NA1 were correctly constructed and could be used to prepare pseudovirus supernatants of high titer by co-transfecting 293T cells with the plasmid pNL4-3.Luc.R-E-. The virus particles were round under electron microscope. H5N1 pseudovirus-infected mice exhibits strong fluorescence signals, which were attenuated by FHA3 treatment before challenge.Conclusions:The in vivo infection model of H5N1 pseudovirus was successfully constructed and FHA3 antibody was proved to be protective against the pseudovirus infection.

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.

Objective: To compare the sedation induced by target-controlled infusion of propofol with that by propofol-remifentanil in third molar exaction surgery. Methods: 60 patients for third molar exaction were divided randomly into 2 groups(n = 30): group P(propofol group) and group PR(propofol-remifentanil group). In group P,a titrated infusion of propofol was started until the OAA/S score had reached level 3 in the patients,then the surgery began. In group PR,a infusion of remifentanil with a target plasma concentration of 1 ng /ml and a titrated infusion of propofol was started until the OAA/S score had reached level 3,then the surgery began. In all patients,the heart rate,blood pressure,respiratory rate,oxyhemoglobin saturation and narcotrend index were recorded during the operation. The reactions of the patients in the operation were recorded. The satisfaction of the patients and surgeons was asked. Results: The respiratory rate and the oxyhemoglobin saturation in group PR was lower than those in group P(P ＜ 0. 05). No obvious adverse reaction was observed in the 2 groups. The satisfaction of the patients in the 2 groups was 30 /30 and 30 /30(P＞ 0. 05). Conclusion: The sedation induced by target-controlled infusion of propofol or propofol-remifentanil in third molar extraction is safe. The sedation under target-controlled infusion of propofol-remifentanil is better than that by propofol when inhalating oxygen.