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Objective To analyze the changes of postoperative pulmonary function in lung transplant recipients. Methods Clinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. Results Postoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity (FVC) to predicted value ratio (FVC%pred), forced expiratory volume in one second (FEV1) to predicted value ratio (FEV1%pred), FEV1/FVC to predicted value ratio (FEV1/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (DLCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV1%pred were gradually increased within postoperative 9 months, and DLCOc%pred was gradually elevated within postoperative 3 months (all P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV1%pred≥80% in 41 cases, FEV1/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 case and FEV1%pred≤40% in 1 case, respectively. Sixteen recipients had DLCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (DLCOc/VA%pred) ≥80% in 63 cases, DLCOc%pred≤40% in 4 cases and DLCOc/VA%pred≤40% in 1 case, respectively. Postoperative FVC%pred, FEV1/FVC%pred and DLCOc%pred in recipients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative DLCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). Conclusions Pulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.
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T cell immunoglobulin and ITIM domain (TIGIT) is a novel immune checkpoint that has been considered as a target in cancer immunotherapy. Current available bioassays for measuring the biological activity of therapeutic antibodies targeting TIGIT are restricted to mechanistic investigations because donor primary T cells are highly variable. Here, we designed a reporter gene assay comprising two cell lines, namely, CHO-CD112-CD3 scFv, which stably expresses CD112 (PVRL2, nectin-2) and a membrane-bound anti-CD3 single-chain fragment variable (scFv) as the target cell, and Jurkat-NFAT-TIGIT, which stably expresses TIGIT as well as the nuclear factor of activated T-cells (NFAT) response element-controlled luciferase gene, as the effector cell. The anti-CD3 scFv situated on the target cells activates Jurkat-NFAT-TIGIT cells through binding and crosslinking CD3 molecules of the effector cell, whereas interactions between CD112 and TIGIT prevent activation. The presence of anti-TIGIT mAbs disrupts their interaction, which in turn reverses the inactivation and luciferase expression. Optimization and validation studies have demonstrated that this assay is superior in terms of specificity, accuracy, linearity, and precision. In summary, this reliable and effective reporter gene assay may potentially be utilized in lot release control, stability assays, screening, and development of novel TIGIT-targeted therapeutic antibodies.
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Objective To evaluate the performance of medical services of 18 tertiary hospitals in Sichuan province in 2016 based on DRGs, to identify objective methods to evaluate service quality and performance of medical institutions.Methods Based on the homepage data of inpatient medical records from 18 tertiary hospitals in Sichuan in 2016, using diagnosis-related groups as a risk-adjustment tool, the study evaluated the medical service quality and performance from three dimensions:medical ability,service efficiency and medical Quality.Results In the evaluation of medical service capacity, hospital I had the highest number of discharged cases and total weight(83 405 cases and 126 522.22),and hospital G had the lowest discharge cases and total weight(2 350 cases,2 797.12).The highest number of DRGs group was from hospital B(661 groups),and the lowest from hospital G(43 groups).The highest value of CMI was from hospital F(2.091),and the lowest from hospital D(0.953).Hospitals B,I and P had wide disease type range,while hospitals F, B and I had higher overall technical level than the other hospitals.Of the service efficiency evaluation,hospital E had the lowest time consumption index(0.740),and hospital P had the lowest expenditure index(1.073).Of the service quality evaluation,hospitals F and G had the lowest risk of mortality and the lower risk of mortality(0.00%,0.00%).Hospital I had the highest total score (100.0 points), and hospital G had the lowest total score(51.1 points).Conclusions DRGs based evaluation on medical service quality and performance of medical institutions can ensure reliability and scientific adequacy of evaluation.It may contribute to the continuous improvement of medical quality, and provide data support and decision reference for medical service supervision.
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<p><b>OBJECTIVE</b>To explore the association between rs659366 polymorphisms and the outcomes of patients after surgery for colorectal cancer.</p><p><b>METHODS</b>The study was conducted among a cohort of 501 patients with primary colorectal cancer who had surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes of the patients were followed up. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect rs659366 genotypes. The log-rank test was performed to analyze the effects of clinical features on patients' outcomes. The correlation between rs659366 polymorphisms and the outcomes of patients was analyzed using the Cox proportional hazard model.</p><p><b>RESULTS</b>In this study, the median of follow-up time was 44.23(0.13-78.53)months, and 101 out of 501 (20.2%) patients failed to follow-up. The log-rank test showed the tumor site, TNM stage, vascular invasion, perineural invasion and the preoperative carcino-embryonic antigen(CEA) level were significantly associated with the outcome of colorectal cancer (<0.05 or <0.01). The overall survival rate of patients with AA, GA and GG genotypes were 62.7%, 69.9% and 75.5%, respectively. Multivariate analysis according to Cox proportional hazard model taking the GG genotype as the reference indicated that the AA genotype increased risks for survival of patients (=1.823); under the dominant genetic model taking GG genotype as reference, GA+AA genotypes increased risks for the poorer outcomes of patients (=1.498); the addictive genetic model showed that allele A increased the hazard for the poorer outcomes (=1.787).</p><p><b>CONCLUSIONS</b>The rs659366 polymorphisms are significantly associated with the outcome of patients with colorectal cancer.</p>
Subject(s)
Humans , Colorectal Neoplasms , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Proportional Hazards Models , Survival Rate , Uncoupling Protein 2ABSTRACT
Objective:In this study,a series of experiments were conducted to research the mechanism of anticancer and preliminary molecular effects of PAMs on the HEPG-2 cancer cells.Methods:Morphological observation and MTT assay were used to explore the inhibition and killing effect of PAMs acting on HEPG-2.AO/EB staining and Annexin V-FITC/PI staining were employed to observe the apoptosis of HEPG-2 treated with PAMs.The expression level of Foxm1,bcl-2 and others genes in HEPG-2 cells were detected by using qRT-PCR and western blot.Wound healing and transwell experiments determined if PAMs can inhibit the migration of HEPG-2.Results:PAMs can inhibit and kill HEPG-2 cells in time and dose-dependent manners,and the cytotoxic effects were closely related to the cell apoptosis.The mRNA expression of foxm1,bcl-2 and surviving gene were remarkably decreased in HEPG-2 cells after the treatment of PAMs.PAMs decreased the FoXM1 protein expression in HEPG-2 cells,while up-regulating thep53 protein expression.,and it could also inhibit the migration of cancer cells.Conclusions:The possible molecular mechanism for the killing of HEPG-2 cancer cells by PAMs was proposed.By down-regulating the expression of foxm1 and up-regulating the expression of p53,the transcriptional expression of their downstream target genes survivin and bcl-2 was inhibited or reduced,hence enhancing the cancer cell apoptosis.This study provides an important foundation for the development of anti-cancer Chinese folk medicine based on PAMs.
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@#In this study, the leukemia K562 cell line was used as a model to elucidate the anticancer effects and preliminary mechanisms of PAMs. MTT assay showed that PAMs could cause cytotoxicities in K562 cells in dose- and time-dependent manners. AO-EB, Annexin-FITC/PI staining showed that the killing effects of PAMs in K562 cells were related to apoptosis, which was further confirmed by the following molecular and enzymatic assay. The mRNA levels of pro-apoptotic genes caspase-3, caspase-9 and bax were remarkably increased while the anti-apoptotic gene bcl-2 was significantly decreased determined by fluorescent quantitative PCR. Western blotting disclosed that PAMs could up-regulate caspase-3 and down-regulate anti-apoptotic survivin protein expression. The latter was also consistent with the results that PAMs could increase the enzymatic activities of both caspase-3 and caspase-9. All these results suggested that PAMs could effectively inhibit the proliferation of K562 cells and the mechanisms may be closely related to apoptosis induction. The work provides evidence basis for PAMs to be potentially developed as anti-cancer leukemia Chinese medicine.
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Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Subject(s)
Humans , Amino Acid Sequence , Matrix Metalloproteinase 14 , Chemistry , Molecular Dynamics Simulation , Neoplasms , Peptide Library , Peptides , ChemistryABSTRACT
OBJECTIVE:To study endothelial NO-dependent vasodilation effect of the extracts of Herba Siegesbeckiae. METHODS:SD rat thoracic aorta rings were used to observe contraction of blood vessel, and the effects of the extracts of Herba Siegesbeckiae on the contraction induced by phenylphrine (PE). RESULTS:The extract of Herba Siegesbeckiae could inhibit the contraction of blood vessel induced by PE. After pretreatment of blood vessel by L-NNA, vasodilation effect of the extracts of Herba Siegesbeckiae was significantly attenuated at low concentration condition(P