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One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce antibody resistance. We engineered two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) increases antigen-binding and virus-neutralizing activities and spectrum against multiple SARS-CoV-2 variants including the Omicron, than the cocktail. X-ray crystallography and computational simulations reveal distinct neutralizing mechanisms for individual cocktail antibodies and suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and the Beta, Gamma, and Delta variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.
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Objective:To investigate the effect of continuous renal replacement therapy on sepsis complicated with acute renal injury and its influence on cytokines and renal function.Methods:From January 2017 to October 2019, 82 patients with sepsis and acute renal injury admitted to the People's Hospital of Jiangshan were divided into control group and observation group according to the random digital table, with 41 cases in each group.The control group was given routine treatment, and the observation group was treated with continuous veno venous hemofiltration(CVVH) on the basis of the control group.The course of treatment in both groups was 5 days.The time of ICU stay and mechanical ventilation, Marshall score, acute physiology and chronic health status scoreⅡ(APACHEⅡ), cytokines and renal function were compared before and after treatment.Results:The ICU stay time[(13.25±1.97)d] and mechanical ventilation time[(11.83±2.43)d] in the observation group were shorter than those in the control group[(11.83±2.43)d and (16.78±1.85)d]( t=9.092, 10.378, all P<0.05). After treatment, the Marshall organ dysfunction score[(5.78±0.81)points] and APACHEⅡ score[(15.40±1.62)points] in the observation group were lower than those in the control group[(7.19±0.67)points and (21.25±3.25)points]( t=8.589, 10.315, all P<0.05). The serum levels of PCT[(7.68±2.10)μg/L] and CRP[(45.41±10.20)mg/L] in the observation group were lower than those in the control group[(13.76±1.78)μg/L and (109.87±12.76)mg/L]( t=14.142, 11.320, 25.266, all P<0.05). The serum levels of BUN[(4.62±0.38)nmol/L] and Scr[(25.45±5.17)μmol/L] in the observation group were lower than those in the control group[(13.79±0.43)nmol/L and (68.79±4.15)μmol/L]( t=20.011, 18.421, all P<0.05). Conclusion:The effect of continuous renal replacement therapy on sepsis combined with acute renal injury is good, which can significantly reduce the inflammatory response of cells and improve the renal function of patients.
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Objective To evaluate the efficacy of an airway topical anesthesia catheter for topical anesthesia using a spray-as-you-go technique via the fiberoptic bronchoscope (FOB).Methods Forty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients with obstructive sleep apnea syndrome,aged 20-64 yr,with body mass index of 23-35 kg/m2,with no upper respiratory tract infection within 1 week before operation,scheduled for elective uvulopalatopharyngoplasty,were divided into 2 groups (n =20 each) using a random number table:routine control group (group C) and FOB-airway topical anesthesia catheter group (group F).In group C,the pharynx and larynx were sprayed with lidocaine FOB by using a laryngo-tracheal mucosal atomization device,and cricothyroid membrane puncture was performed and then lidocaine was injected.In group F,airway topical anesthesia was performed using a spray-as-you-go technique via the FOB with an airway topical anesthesia catheter spraying lidocaine via the nose.At 5 min after topical anesthesia of the airway,FOB-guided intubation was performed,and dexmedetomidine was intravenously infused at 0.1 μg · kg-1 · min-1 for sedation in both groups.Ramsay sedation scores were assessed after topical anesthesia and before intubation.The scores for the intubating condition and tolerance of tracheal tube were assessed during FOB-guided intubation.Successful intubation and the development of responses to intubation and hypoxemia were recorded.The patients were followed up one day after the end of operation,and parents' satisfaction with the procedure of intubation was recorded.Results Compared with group C,the intubating condition score,tolerance of tracheal tube score,success rate of intubation at first attempt and rate of parents' satisfaction with the procedure of intubation were significantly increased,and the incidence of responses to intubation was decreased (P<0.05),and no significant change was found in Ramsay sedation scores before intubation and incidence of hyoxemia in group F (P>0.05).Conclusion When the FOB is used to guide awake nasotracheal intubation,the airway topical anesthesia catheter provides better efficacy,better intubating conditions,and fewer side effects when applied for topical anesthesia using a spray-as-you-go technique via the FOB,it can be easily accepted by the patients and the efficacy is better that of routine airway topical anesthesia.
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Objective To explore the treatment of the ICU ventilator associated pneumonia(VAP),and the prevention strategy.Methods Analyzed the clinical features and microbiological data of 80 ICU VAP patients. Results The main pathogenic bacterias of VAP were acinetobacter baumannii and pseudomonas aeruginosa,which were Gram negative bacteria.A total of 200 strains pathogenic bacteria were isolated,in which,Gram negative bacteria reached to 76.0%,which mainly including:acinetobacter baumannii strains,klebsiella pneumoniae,pseudomonas aeruginosa and so on.24.0% was Gram positive bacteria,including staphylococcus aureus accounted for 10.5%,and the epidermis staphylococcus,hemolysis staphylococcus and so on.Proportion of fungi was 11.0%.According to the results of microbiological data,the effective anti-microbial treatments were administered.After treatments for 10 days, the VAP infection parameters(including temperature,the white blood cell count and the number of strains)were grad-ually back to normal.Conclusion The main VAP pathogenic bacteria are Gram negative bacteria,patients commonly are infected by two or more bacterias,which lead to the multiple infection,the treatment should be fully based on mi-crobiology and clinical monitoring data,and the formulating personalization antibacterial treatment.
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Objective To explore the expression of transient receptor potential channel 6(TRPC6)in human breast cancer cells, and to clarify the correlation of TRPC6 with the invasion potential of breast cancer cells. Methods The human breast cancer cell strains MCF-7 (hypo-invasion group)and MDA-MB-231 (hyper-invasion group)were cultured.The expressions of TRPC6 mRNA and protein in in two groups were detected by RT-PCR and Western blotting methods.Then the MDA-MB-231 cells were divided into control group and SKF96365 group, the effects of SKF96365 on the invasion ability of MDA-MB-231 cells invitro were explored by wound healing assay and Transwell experiment.Results The results of Western blotting and RT-PCR showed that the expression levels of TRPC6 mRNA and protein in MDA-MB-231 cells were higher than that in MCF-7 cells(P<0.05).The wound healing assay showed the numbers of migrating cells in 5,25 and 40μmol·L-1 SKF96365 groups (76.24±7.54, 45.33±4.50,25.12±1.57)were lower than those in control group (130.48±9.55)(P<0.05).The Transwell experiment results indicated that the invasiveness of MDA-MB-231 cells were inhibited significantly by SKF96365 compared with control group (P<0.05).Conclusion The invasion ability of human breast cancer MDA-MB-231 cells is promoted by upregulating the TRPC6 expression, which indicates that the TRPC6 may play role in the metastasis of human breast cancer.
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Objective To evaluate the efficacy of T-joint endoscopy mask for fiberoptic bronchoscopy (FOB)-guided awake nasotracheal intubation in patients with cervical spinal cord injury.Methods Forty patients of both sexes aged 21-64 yr with fracture of cervical spine complicated by spinal cord injury scheduled for anterior decompression and interbody fusion under general anesthesia were randomly divided into 2 groups according to the technique for awake nasotracheal intubation (n =20 each):group nasal catheter and group T-joint endoscopy mask.Topical anesthesia of nasal cavity,pharynx,larynx and trachea with 2% lidocaine was conducted and then remifentanil was continuously infused at 0.05-0.15 μg· kg-1 · min-1 in both groups.The incidence of hypoxemia and intubation time were recorded.Arterial blood samples were obtained for determination of PaO2 and PaCO2 before topical anesthesia (baseline),immediately before and 1 min after placement of FOB and immediately after nasotracheal intubation was accomplished.Results The incidence of hypoxemia was significantly lower in group Tjoint endoscopy mask (0) than in group nasal catheter (25%) (P < 0.05).The PaO2 during nasotracheal intubation was significantly higher in group T-joint endoscopy mask than in group nasal catheter (P < 0.05).There was no significant difference in PaCO2 and intubation time between the 2 groups (P > 0.05).Conclusion T-joint endoscopy mask facilitates awake nasotracheal intubation without affecting oxygen inhalation in patients with cervical spinal cord injuries.
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Objective To investgate the changes in the expression of hepatocyte growth factor (HGF)and c-met in the lungs in a rat model of pulmonary hypertension.Methods Eighty 7 week old male SD rats weighing 180-250 g were randomly divided into 2 groups ( n =40 each ):control group (group C) and pulmonary hypertension group (group PH).Pulmonary hypertension was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg 2 weeks later.Pulmonary artery pressure and the ratio between the weight of right ventricle and left ventricle + interventricular septum ( RV/LV + S) were measured at 7,14,21 and 28 d after MCT administration.HGF and c-met protein and mRNA expression and TGF-β content in the lung tissue were determined.Results Pulmonary hypertension and right ventricular hypertrophy associated with hypertrophy of pulmonary artery tunica media and muscularization of small pulmonary arteries developed after MCT administration in PH group.In PH group HGF protein and mRNA expression in the lungs was significantly down-regulated as compared with group C.There were no significant differences in c-met protein and mRNA expression in the lungs between the 2 groups.The TGF-β content in the lungs was significantly increased in group PH as compared with group C.Conclusion Decrease in HGF production in the lungs plays an important role in the pulmonary hypertension.Increasing of pulmonary TGF-β may play an important role in the down-regulation of pulmonary HGF expression during pulmonary hypertension.
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Objective To construct F344 rat bone marrow mesenchymal stem cell line (MSC) modified with human hepatocyte growth factor (hHGF) gene.Methods Recombinant virus containing hHGF was obtained by transfecting the packaging cell line 293 FT with lentiviral vector pLV/EF1α-hHGF-IRES-eGFP.MSCs derived from F344 rat bone marrow were then tranfected with packed lentiviral vector.Purified MSCs expressing hHGF was obtained by screening culture with G418.MSCs and MSCs transfected with empty vector were used as control.The expression of hHGF protein was detected by Western blot (eGFP-MSCs).The hHGF-transfected MSCs were cultured in osteoblast-inducing culture medium and osteoblast phenotype was assayed by alizarin Red staining.The cells were also cultured in adipogenesis medium and stained with Oil Red O for identification.Results The expression of hHGF protein was significantly up-regulated in the hHGF-MSCs as compared with MSCs and eGFP-MSCs.hHGF-MSCs readily differentiated into mineralizing cells or adipocytes when incubated in differentiation medium.Conclusion A F344 rat MSC line that stably expresses HGF is successfully established.
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Objective To analyse the effects of anastomat to the resection surgery in 1800 esophageal and gastric cardiac carcinoma patients. Methods The Esophagus-gaster and Esophagus-intestine were stapled by anastomat in the cervical region in 182 cases、 intrathoracically in 1296 cases and intraperitoneal in 322cases. The occurrence of complications caused by anastomat, including anastomotic fistula,anastomotic stricture,anastomotic bleeding and mechanical failure,were observed. Results Anastomotic fistula occurred in 15 cases ( 15/1800,0.83% ,ten cases took Shanghai-made GF-I anastomat ,five cases took YH-W single disposable single anastomat ), among which 6 cases had the cervical anastomosis; Anastomotic stricture occurred in 41 cases ( 41 /1800,3.11%, fifteen cases took Shanghai-made GF-I anastomat, twenty-six took YH-W single disposable single anastomat) ,but all of them recovered after dilatation; Anastomotic bleeding occurred in 21 cases (21/18001.16%, thirteen cases took Shanghai-made GF-I anastomat, eight took YH-W single disposable single anastomat) ;Anastomat mechanical failure in operation occurred in 14 cases( 14/1800,0. 78% ,ten cases took Shanghai-made GF-I anastomat, four took YH-W single disposable single anastomat). Conclusion Anastomat is an effective method in reducing the postoperational complications of esophageal and gastric cardiac carcinoma resection. Disposable single anastomat has higher clinical value.
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@#Objective To investigate the effects of body-weight support treadmill training(BWSTT) on function of lower limbs.Methods 46 hemiplegic patients after stroke were randomly divided into the therapy group(n=23) and control group(n=23).The subjects of both groups were administered with standardized rehabilitation program.The therapy group was also given BWSTT in addition.Both groups were evaluated before and after treatment using Functional Ambulation Category(FAC),Fugl-Meyer Assessment(FMA),Berg Balance Scale(BBS).Results Before treatment,there was no significant difference between these 2 groups in terms of scores with FAC,FMA and BBS.After treatment,both groups were significantly improved regard to their scores with FAC,FMA and BBS(P<0.01),with the therapy group scored significantly better than the control group(P<0.01).Conclusion BWSTT can significantly improve walk ability and balance function of the hemiplegic patients after stroke.
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Seventeen organic phosphorus pesticides (OPs) and 18 organic chlorine pesticides (OCs) at water from Jiulong River Estuary (JLRE) are determined by SPE-GC-(FPD and microECD). The contents of the total OPs (17) ranged from 134.8 to 354.6 ng/l (the mean is 227.2 ng/l). Total OCs concentrations varied from 115.4 to 414.7 ng/l in water (mean 237.7 ng/l). The levels of total hexachlorocyclohexane in water varied from 31.95 to 129.8 ng/l (mean 62.51 ng/l), and those of total DDTs were in the range 19.24-96.64 ng/l (mean 48.69 ng/l). The distribution and behavior characteristics of OPs indicate that five main OPs (methamidophos, dichlorvos, malathion, omethoate and dimethoate) occupied the most part of the total OPs, in addition, the sources of the OPs (mainly from current usage) are not stable. While the OCs mainly came from early application and were more stable. The OPs did not have obvious correlation with the dissoved organic carbon and suspended particulate matter at water from JLRE. It maybe due to the complicated hydrological kinetics in the estuary, and the higher water solubility and weak absorption (with organic matter) action of OPs. When compared with other areas, the OPs and OCs level in JLRE are some moderate.
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Hidrocarburos Clorados , Insecticidas/análisis , Compuestos Organofosforados , Contaminantes Químicos del Agua/análisis , Absorción , China , Monitoreo del Ambiente , Cinética , Tamaño de la PartículaRESUMEN
Objective Calcitonin gene-related peptide (CGRP), neurotensin (NT) and atrial natriuretic polypeptide (ANP) have strong vaso-dilating and positive inotropic action, whereas neuropeptide Y (NPY) and endothelin (ET) have vaso-constricting effect. They all have profound effects on hemodynamics. The purpose of this study was to examine the changes in the 5 neuropeptides in elderly hypertensive patients under general anesthesia.Methods The control group comprised eight men and six women without hypertension with a mean age of (69?8)yr. The hypertension group included nine men and five women with a mean age of (71?9)yr. The patients in the hypertension group had different degrees of myocardial hypertrophy and ST-T changes. All 28 patients underwent upper abdominal surgery. Anesthesia was induced with propofol 2mg?kg -1 and fentanyl 2?g?kg -1 and intubation was facilitated with succinylcholine 2mg?kg -1. The patients were mechanically ventilated after intubation. Anesthesia was maintained with 50% N 2O and enflurane or isoflurane inhalation supplemented with intermittent doses of vecuronium. Venous blood samples were taken before anesthesia, 3min after intubation, 60 min after start of surgery, at the end of surgery and 24 h after operation for determination of plasma levels of CGRP, NT, ANP, NPY and ET by radioimmunoassay.Results In hypertension group plasma level of ANP decreased and NPY increased significantly at the end of operation and 24 h after operation (P