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Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment. .
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Humans , Adenocarcinoma of Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/therapeutic useABSTRACT
@#To investigate the effects of VHL (von Hippel-Lindau) inhibitor on Caenorhabditis elegans (C.elegans) model of Parkinson''s disease (PD),C.elegans were exposed to rotenone and treated with VHL inhibitor VH298.The death,dopaminergic neurodegeneration and mitochondrial unfolded protein response (mito-UPR) of transgenic strains with the markers zcIs9 and otIs181 exposed to different concentrations of rotenone were investigated. The death,dopaminergic neurodegeneration,and changes of behaviors including head thrashes,body bends and foraging behavior of C.elegans model of PD treated with different concentrations of VH298 were explored.The results showed that different concentrations of rotenone can lead to the death,dopaminergic neurodegeneration and abnormal mito-UPR of transgenic nematodes with zcIs9; otIs181,while the VHL inhibitor can decrease the death rate and alleviate dopaminergic neurodegeneration of rotenone-induced C.elegans model of PD.The VHL inhibitor can also attenuate the behavioral abnormalities of head thrashes,body bends and foraging behavior of C.elegans model.These results suggest that rotenone may cause mitochondrial damage in the transgenic nematodes with zcIs9; otIs181, and then destroy mitochondrial homeostasis,thereby resulting in dopaminergic neurodegeneration and death of the nematodes. The VHL inhibitor VH298 may promote the survival of rotenone-induced C.elegans model of PD,and alleviate dopaminergic neurodegeneration,thereby improving the behavioral abnormalities of C.elegans model of PD.
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The increase in prevalence of diabetes in India is one of the leading causes of blindness due to micro vascular and macro vascular complications. The complications in retina and kidney are due to damage of small vessels. Studies have shown significant association between diabetic retinopathy and diabetic nephropathy. In our study, we are discussing the complications during intra and post-operative period and also both anatomical and functional outcome in these patients after vitrectomy for proliferative diabetic retinopathy. Both eye and kidney share same vascular pattern. One pre-existing condition can be followed by the other condition due to similar microvascular damage. We wanted to evaluate the outcome of vitrectomy in proliferative diabetic retinopathy patients associated with chronic kidney disease.METHODSThis is a retrospective study done at Sarojini Devi Eye Hospital, Telangana State, South India, over a two-year period from June 2017 to June 2019. Data was collected from old medical records of our institute, from patients who presented to Retina Dept. with various complaints. They were examined in detail, documented and treated based on clinical presentation after clearance from physician. Patients presented with different ocular manifestations like non-resolving vitreous haemorrhage, focal tractional retinal detachment, multi focal tractional retinal detachment like broad based, table top, combined retinal detachment and tractional maculopathy. Patients underwent pars plana vitrectomy with or without silicone oil endotamponade.RESULTSPrognosis in these patients was good only in cases of non-resolving vitreous haemorrhage and focal tractional retinal detachment (47.61%) whereas in cases like multifocal retinal detachment cases outcome was favourable (42.82%) but patients with combined retinal detachment (9.52%) had poor anatomical and visual outcome.CONCLUSIONSManagement of these patients is very difficult when there is severe proliferative diabetic retinopathy with multiple broad vitreo retinal adhesions. Outcome is very poor particularly in patients of severe proliferative diabetic retinopathy associated with chronic kidney disease and coronary artery disease due to intra operative complications
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Objective@#To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features.@*Methods@#We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled.@*Results@#Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively.@*Conclusions@#Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
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Objective@#To isolate the cross-reactive antibodies against hemagglutinin of influenza virus and identify its biological function.@*Methods@#The antibodies gene reservoir of cross-reactive and H5N1 pseudotype particles neutralizing B cell circulating in peripheral blood of a human H5N1 case was recovered by in vitro B cell culture, screening, RT-PCR and expression vector cloning techniques. The Ab gene pairing was screened by transient transfection of human kidney 293T cells and detected using ELISA and neutralization test. The heterosubtypic antibodies were prepared and characterized.@*Results@#We discovered the VH1-2-based heterosubtypic antibodies from two B cell lineages could neutralize GX-H5N1 pseudotype particles and have broader binding with Group 1 (including H1, H5, H6 and H9) and H7 subtype.@*Conclusions@#Cross-reactive antibodies can be induced by H5N1 infection.
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Resumen Introducción Durante la etapa aguda de la infección por el Virus de la Hepatitis B (VHB) y el período inicial de una infección crónica, el DNA está en forma episomal (libre o extracromosomal) y se replica en el hepatocito produciendo, entre otros, viriones infectivos, DNA polimerasa y antígeno de superficie del virus (HBsAg). Objetivo Validar un inmunoensayo tipo ELISA para cuantificar los niveles de HBsAg en pacientes con hepatitis B crónica. Método Se realizó un estudio experimental de desarrollo tecnológico. Se llevó a cabo la normalización y validación de un inmunoensayo enzimático heterogéneo de doble anticuerpo para la cuantificación de HBsAg en sueros de seres humanos. 115 muestras de pacientes con hepatitis B crónica con resultados de carga viral se correlacionaron con las concentraciones de HBsAg. Resultados y discusión El método presentó coeficientes de variación intra e interensayo de 9,8 y 13,2% respectivamente. El rango de trabajo se estimó entre 0.15 y 60 ng/mL. El porcentaje de recuperación estuvo entre el 90 y 110% y el ajuste lineal de la curva estándar presentó un coeficiente de determinación superior a 0,99. La correlación alcanzada entre los niveles de DNA y la concentración de HBsAg fue de 62.5%. Conclusiones La evaluación del ELISA para la cuantificación de HBsAg desarrollado en el laboratorio mostró que cumple los parámetros de validación para su uso clínico.
Abstract Introduction During the acute phase of infection with Hepatitis B Virus (HBV) and the initial period of chronic infection, DNA is episomally (free or extrachromosomal) and replicates in hepatocytes producing among other virions, DNA polymerase and virus surface antigen (HBsAg). Objective Validate an ELISA to quantify HBsAg levels in patients with chronic hepatitis B. Method An experimental study of technological developmentwas conducted. The normalization and validation of heterogeneous double antibody enzyme linked inmunoassay for quantitation of HBsAg in human sera was carried out. 115 serum samples from patients with chronic hepatitis B with viral load results were correlated with its HBsAg concentrations. Results and discussion The developed method presented variation coefficients intra and interassay of 9.8 and 13.2% respectively. The working range was estimated between 0.15 and 60 ng/mL. The recovery rate was between 90 and 110% and the linear fit of the standard curve presented a determination coefficient greater than 0, 99. The correlation between the DNA levels and HBsAg concentration was 62.5%. Conclusions The assessment of the ELISA for quantitation of HBsAg developed in the laboratory showed that it achieved validation parameters for its clinical use.
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Objective To construct the prokaryotic expression vector pET30a( +)-VH-mms13 and identification of its protein after induced with IPTG.Method Heavy chain variable region VH gene of typeⅣcollagenase monoclonal antibody and magnetosome membrane protein gene mms13 were amplified separately,the fusion gene VH-linker-mms13 were synthesized by SOE-PCR technique and inserted into pET30a ( +) plasmid, which was confirmed by restriction enzyme digest and sequencing.Then the recombinant plasmid pET30a ( +)-VH-mms13 was transform into E.coli DE3 and induced with 0.4 mmol/L IPTG.The fused protein was identified by SDS-PAGE and Western blot.Results The length of fusion gene VH-mms13 was 738 bp,and the sequence was correct.After induced with IPTG,the fused protein was found in the inclusion body and Western blot results suggested that the fused protein can bind with His-tag antibody specifically.Conclusion Expression vector pET30a ( +)-VH-mms13 is successfully constructed and the fusion protein has good immunogenicity,which lay the foundation for the development of biomagnetism-targeted drug.
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PURPOSE: The aim of this study was to demonstrate the early effects of statin treatment on plaque composition according to plaque stability on Intravascular Ultrasound-Virtual Histology at 6 months after a coronary event. Previous trials have demonstrated that lipid lowering therapy with statins decreases plaque volume and increases plaque echogenicity in patients with coronary artery disease. MATERIALS AND METHODS: Fifty-four patients (54 lesions) with acute coronary syndrome were prospectively enrolled. We classified and analyzed the target plaques into two types according to plaque stability: thin-cap fibroatheroma (TCFA, n=14) and non-TCFA (n=40). The primary end point was change in percent necrotic core in the 10-mm subsegment with the most disease. RESULTS: After 6 months of statin therapy, no change was demonstrated in the mean percentage of necrotic core (18.7+/-8.5% to 20.0+/-11.0%, p=0.38). There was a significant reduction in necrotic core percentage in patients with TCFA (21.3+/-7.2% to 14.4+/-8.9%, p=0.017), but not in patients with non-TCFA. Moreover, change in percent necrotic core was significantly correlated with change in high-sensitivity C-reactive protein levels (r=0.4, p=0.003). Changes in low-density lipoprotein cholesterol levels and lipid core percentage demonstrated no significant associations. CONCLUSION: A clear reduction of lipid core was observed only for the TCFA plaque type, suggesting that changes in plaque composition following statin therapy might occur earlier in vulnerable plaque than in stable plaque; the effect may be related to the anti-inflammatory effects of statins.
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Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome/drug therapy , C-Reactive Protein/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Plaque, Atherosclerotic/diagnostic imaging , Ultrasonography, InterventionalABSTRACT
PURPOSE: Donor site seroma is the most common complication of extended latissimus dorsi flap for breast reconstruction. One of preventive treatments is to use the fibrin sealant in donor site before closure. Experimentally, it has been used successfully in the prevention of latissimus donor site seroma, but its clinical efficacy and results were very controversial. Thus, the purpose of this study is to evaluate the clinical efficacy and to determine the optimal dose of fibrin sealant. METHODS: A retrospective study was done of patients operated under same surgical conditions by one operator with variable doses of fibrin sealant. The study group consisted of 60 consecutive patients who underwent breast reconstruction with extended latissimus flap reconstructions from January 2005 to December 2006. Patients were divided into 4 group by applied fibrin sealant amount(group 1=0mL, group 2=1mL, group 3=2mL, group 4=4mL). Retrospective data were obtained from total postoperative drainage amount, time from surgery to drain removal, and incidence and quantity of seroma formation in matched patients group. RESULTS: Total drainage amount decreased relative to the amount of fibrin sealant. The seroma formation rate of 30% in the study group 4 was significantly less than group 1 rate of 71%(p<0.05). It was an improvement over the rates of as much as 79% described previously in the literature. Also, time from surgery to drain removal was shortened significantly in group 4 patients (p<0.05). CONCLUSION: The use of fibrin sealant in the extended latissimus dorsi flap donor site appears effective in preventing seroma. However, important factors to obtain lower seroma formation rates are proper techniques and proper amounts such as the authors suggested amount: 0.01mL/cm2 with spray type fibrin sealant.
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Female , Humans , Drainage , Fibrin , Fibrin Tissue Adhesive , Incidence , Mammaplasty , Retrospective Studies , Seroma , Tissue DonorsABSTRACT
It already has been known that various ions were participated in phototransduction mechanism of the vertebrate photoreceptor during the visual adaptation. The vitreous humor(VH)contains certain amount of Na+, K+ and Ca++ as well. However, the roles of these ions are unknown except functioning of metabolic process. Our preliminary electroretinogram(ERG) experiments suggested that the permeability of these ions has light dependent activity during the light illumination. We have supported this suggestion more tangibly by trying out various experiments with bullfrog eyes as a reference of visual adaptation. The results are summarized as follows: 1)According to our atomic absorption spectroscopic measurements, the concentration of Na+, K+ and Ca++ in light adapted VH was higher than that of dark adapted VH. This result indicated that the light-dependention transport systems which affect the ionic movements might be in internal limiting membrane(ILM). 2)The amplitude of ERG b-wave was reduced by concentration decrement of Na+ and concentration increment of K+ respectively. On the other hand, the elimination of Ca++ within ringer solution resulted in b-wave amplitude increment. 3)Treatment of Na+ hannel blockers(TTX, STX)and K+ channel blockers(Ba++, Cd++, Cs+, 4-AP and TEA)in the vitreous humor side induced the increment and the decrement of b-wave response respectively. Taken together, these results suggest that the light dependent Na+ K+ channels exist in the ILM of vertebrate retina which participates visual adaptation.
Subject(s)
Absorption , Hand , Ions , Light Signal Transduction , Lighting , Membranes , Metabolism , Permeability , Photoreceptor Cells, Vertebrate , Rana catesbeiana , Retina , Vertebrates , Vitreous BodyABSTRACT
BACKGROUND: Refractory edema in some patients with advanced heart failure or renal failure will not respond to diuretic therapy. In this setting, the ex- cess fluid can be removed by continuous hemofiltration either by continuous arteriovenous hemofiltration (CAVH) or continuous venovenous hemofiltration (CVVH). Careful monitoring is required to prevent life-threatening hypotension due to continued production of large ultrafiltrate. To overcome these disadvantages of CVVH, we attempted to perform daytime 1VVH as an alternative therapeutic modality to CVVH. METHODS: We performed venovenous hemofiltration for eight hours in the daytime in dialysis unit and repeated intermittently at 1 or 2 days interval if further treatment is required. We called this intermittent venovenous hemofiltration(IVVH). From October 1992 through November 1997, we prospectively studied the efficacy and usefulness of IVVH in 42 patients with refractory edema. RESULTS: Underlying disorders which required IVVH were renal insufficiency in 28 patients and nephrotic syndrome in 14 patients. The mean duration of treatment was 17.0+/-8.4 hours. Total UFR was 26.1+/-153L and mean UFR/hr was 1.5+/-2.2L. Edema was successfully controled with only one time treatment of IVVH in 12(28.6%), two in 17(40.5%), three in 7(16.6%), four in 4(9.5%), and five in 2(4.8%), Mean number of IVVH treatments per patient was 2.2+/-0.4 to complete the treatment of refractory edema. Changes in blood chemistry and hemodynamics before and after IVVH were not significantly different. Body weight and abdominal girth decreased significantly after IVVH(p<0.001). No major complications occurred during these trials. There were only two episodes(5.1%) of transient hypotension, and each one episode(2.6%) of bleeding at access site and arrhythmia, respectively. CONCLUSION: These results stongly suggest that IVVH is a simple, safe and effective method in the treatment of refractory edema not responding to diuretic therapy.
Subject(s)
Humans , Arrhythmias, Cardiac , Body Weight , Chemistry , Dialysis , Edema , Heart Failure , Hemodynamics , Hemofiltration , Hemorrhage , Hypotension , Nephrotic Syndrome , Prospective Studies , Renal InsufficiencyABSTRACT
Type V hyperlipoproteinemia result from the accumulation of trglyceride(TG)-rich lipoproteins, very low density lipoprotein(VLDL), and chylomicrons. A 53-year old woman has showed asmptomatic, yellowish patches on tie palms and eyelids and papules on the knees with various types of xanthoma including xanthelasma palpebraum, xanthoma striatum palmare, anrl nonspecific papular xanthoma. The blood chemistry revealed a marked elevation of cholesterol and TG, and lipoprotein electrophoresis showed fasting chylomicronemia, prep-b and b-band, On histologic studies, typical foam cells were shown.