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1.
Microbiome ; 8(1): 155, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158461

RESUMO

BACKGROUND: Genome-centric approaches are widely used to investigate microbial compositions, dynamics, ecology, and interactions within various environmental systems. Hundreds or even thousands of genomes could be retrieved in a single study contributed by the cost-effective short-read sequencing and developed assembly/binning pipelines. However, conventional binning methods usually yield highly fragmented draft genomes that limit our ability to comprehensively understand these microbial communities. Thus, to leverage advantage of both the long and short reads to retrieve more complete genomes from environmental samples is a must-do task to move this direction forward. RESULTS: Here, we used an iterative hybrid assembly (IHA) approach to reconstruct 49 metagenome-assembled genomes (MAGs), including 27 high-quality (HQ) and high-contiguity (HC) genomes with contig number ≤ 5, eight of which were circular finished genomes from a partial-nitritation anammox (PNA) reactor. These 49 recovered MAGs (43 MAGs encoding full-length rRNA, average N50 of 2.2 Mbp), represented the majority (92.3%) of the bacterial community. Moreover, the workflow retrieved HQ and HC MAGs even with an extremely low coverage (relative abundance < 0.1%). Among them, 34 MAGs could not be assigned to the genus level, indicating the novelty of the genomes retrieved using the IHA method proposed in this study. Comparative analysis of HQ MAG pairs reconstructed using two methods, i.e., hybrid and short reads only, revealed that identical genes in the MAG pairs represented 87.5% and 95.5% of the total gene inventory of hybrid and short reads only assembled MAGs, respectively. In addition, the first finished anammox genome of the genus Ca. Brocadia reconstructed revealed that there were two identical hydrazine synthase (hzs) genes, providing the exact gene copy number of this crucial phylomarker of anammox at the genome level. CONCLUSIONS: Our results showcased the high-quality and high-contiguity genome retrieval performance and demonstrated the feasibility of complete genome reconstruction using the IHA workflow from the enrichment system. These (near-) complete genomes provided a high resolution of the microbial community, which might help to understand the bacterial repertoire of anammox-associated systems. Combined with other validation experiments, the workflow can enable a detailed view of the anammox or other similar enrichment systems. Video Abstract.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33136395

RESUMO

Assigning disulfide linkage is a crucial task for protein identification. The current bottom-up proteomics workflow has limitations in characterizing peptide digests containing multiple disulfide bonds due to the difficulty of controlling partial reduction via conventional chemical reduction methods. Previously, our lab reported the development of an acetone/2-propanol (IPA) photoinitiating system for rapid (on second time scale) and tunable disulfide bond reduction. Herein, we incorporated this reaction system onto a liquid chromatography-mass spectrometry (LC-MS) system for bottom-up protein analysis applications. The photochemical reduction reaction was implemented in a flow microreactor which allowed for up to 15 s 254 nm UV irradiation. The microreactor was installed post LC separation and right before electrospray ionization, while a T-junction was used to introduce the photoinitiating solution to the LC eluent before entering the microreactor. The degree of disulfide reduction was tunable from partial reduction to complete reduction for peptides containing one or multiple disulfide bonds. Significantly improved sequence coverage was obtained from complete disulfide reduction, while assignment of the disulfide connectivity was facilitated from partial disulfide reduction when coupled with tandem mass spectrometry via collision-induced dissociation. As a proof-of-concept test, trypsin digests of lysozyme (four disulfide bonds) and bovine serum albumin (BSA, 17 disulfide bonds) were analyzed by the LC-MS system coupled with online reduction. Sequence coverage was improved from 35% to 100% and 13% to 87% for lysozyme and BSA, respectively. All four disulfide bonds of lysozyme were determined. For BSA, nine disulfide bonds were characterized and eight adjacent disulfide bonds were narrowed down.

3.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33112406

RESUMO

PURPOSE: Stomach adenocarcinoma (STAD) is one of the most common malignant tumors, and its occurrence and prognosis are closely related to inflammation. The aim of the present study was to identify gene signatures and construct an immune-related gene (IRG) prognostic model in STAD using bioinformatics analysis. METHODS: RNA sequencing data from healthy samples and samples with STAD, IRGs, and transcription factors were analyzed. The hub IRGs were identified using univariate and multivariate Cox regression analyses. Using the hub IRGs, we constructed an IRG prognostic model. The relationships between IRG prognostic models and clinical data were tested. RESULTS: A total of 289 differentially expressed IRGs and 20 prognostic IRGs were screened with a threshold of P<0.05. Through multivariate stepwise Cox regression analysis, we developed a prognostic model based on seven IRGs. The prognostic model was validated using a GEO dataset (GSE 84437). The IRGs were significantly correlated with the clinical outcomes (age, histological grade, N, and M stage) of STAD patients. The infiltration abundances of dendritic cells and macrophages were higher in the high-risk group than in the low-risk group. CONCLUSIONS: Our results provide novel insights into the pathogenesis of STAD. An IRG prognostic model based on seven IRGs exhibited the predictive value, and have potential application value in clinical decision-making and individualized treatment.

4.
Org Lett ; 22(21): 8261-8266, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021794

RESUMO

A visible-light-promoted metal-free catalytic system was developed to achieve the aminothiolation of α-bromocinnamaldehydes. This mechanistically novel approach allows the synthesis of diverse imidazo[2,1-b]thiazole derivatives in satisfactory yields at room temperature under visible-light irradiation by incorporation of two distinct photoinduced processes. The reaction features readily accessible feedstocks, easy operation, mild reaction conditions, and wide reaction scope.

5.
Anal Chem ; 92(21): 14775-14782, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33052665

RESUMO

Sphingomyelins (SMs) are an essential class of lipids widely existing in different organisms. The sphingoid base and N-acyl chain are two building blocks which can undergo different types of modifications during lipogenesis, including desaturation, hydroxylation, and methyl branching. Current lipidomic analysis methods cannot provide detailed information on these structural motifs. Herein, we developed a tandem mass spectrometric method by harnessing radical-directed dissociation (RDD) from collision-induced dissociation (CID) of the bicarbonate anion adduct of SM ([M + HCO3]-). A major RDD channel produced a high-abundance fragment carrying the intact N-acyl chain, termed as "N-acyl fragment", allowing the assignment of the sphingoid base/N-acyl composition and relative quantitation of compositional isomers of SM at high sensitivity. RDD also produced intrachain fragments in lower abundances, which helped localization of methyl branching and hydroxylation in SM. The acetone Paternò-Büchi (PB) reaction was found to be capable of derivatizing the Δ4 carbon-carbon double bond (C═C) in sphingosine (SPH) base and producing C═C diagnostic ions upon CID, albeit at much lower efficiencies than those of the isolated C═C in alkyl chains. A liquid chromatography-mass spectrometry workflow was developed by incorporating MS2 CID of SM via [M + HCO3]- and PB-MS2 CID. The capability of profiling SM with detailed structural information was demonstrated by analyzing complex lipid extracts from porcine brain and Caenorhabditis elegans. These results provided visualization of the sphingoid base/N-acyl compositional isomers of SM lipids and revealed large structural diversity from each sample. These included identification of the sphingadiene base [d18:1(Δ4,14)], C═C location isomers in N-acyls, C-2 hydroxylation of N-acyls, and iso-methyl branched SPH base.

6.
J Clin Pharm Ther ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016519

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood. In this study, we explored the effects of genetic variations on sevoflurane-induced hypnosis. METHODS: Sixty-six SNPs in 18 candidate genes were genotyped using MALDI-TOF MassARRAY in a discovery cohort containing 161 patients administered sevoflurane. Significant polymorphisms were assessed in a validation cohort containing 265 patients. RESULTS AND DISCUSSION: Three polymorphisms (GRIN1 rs28681971, rs79901440 and CHRNA7 rs72713539) were significantly associated with the time to loss of consciousness in patients treated with sevoflurane in the discovery cohort; among them, GRIN1 rs28681971 showed a significant association even after false discovery rate (FDR) correction (pFDR  = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (pFDR  = 0.027, 0.034). Combined assessments and meta-analysis of the results of the two cohorts indicated that the C carriers of rs28681971 and T carriers of rs79901440 in GRIN1 require a longer time to achieve unconsciousness. WHAT IS NEW AND CONCLUSION: These findings suggest that GRIN1 polymorphisms are associated with sevoflurane-induced unconsciousness. Thus, the genotypes of GRIN1 may serve as novel and meaningful biomarkers for sevoflurane-induced unconsciousness.

7.
Crit Rev Food Sci Nutr ; : 1-18, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030031

RESUMO

Sweet tea (Lithocarpus polystachyus Rehd.) has been consumed as herbal tea to prevent and manage diabetes for a long time. Recent studies indicate that sweet tea is rich in a variety of bioactive compounds, especially a class of nonclassical flavonoids, dihydrochalcones. In order to provide a better understanding of sweet tea and its main dihydrochalcones on human health, this review mainly summarizes related literature in the recent ten years, with the potential molecular mechanisms emphatically discussed. Phlorizin, phloretin, and trilobatin, three natural sweeteners, are the main dihydrochalcones in sweet tea. In addition, sweet tea and its dihydrochalcones exhibit plenty of health benefits, such as antioxidant, anti-inflammatory, antimicrobial, cardioprotective, hepatoprotective, antidiabetic, and anticancer effects, which are associated with the regulation of different molecular targets and signaling pathways. Therefore, sweet tea, as a rare natural source of dihydrochalcones, can be processed and developed into nutraceuticals or functional foods, with the potential application in the prevention and management of certain chronic diseases.

8.
Int J Biol Macromol ; 165(Pt A): 1303-1311, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022346

RESUMO

Conidial hydrophobins in fungal pathogens of plants, insects, and humans are required for fungal attachment and are associated with high virulence. They are believed to contribute to the pathogenesis of infection by preventing immune recognition. Here, we refute this generalisation offering a more nuanced analysis. We show that MacHYD3, a hydrophobin located on the conidial surface of the specialist entomopathogenic fungus Metarhizium acridum (narrow host range, kills only locusts and grasshoppers), activates specifically the humoral and cellular immunity of its own host insect, Locusta migratoria manilensis (Meyen) but not that of other non-host insects. When topically applied to the cuticle, purified MacHYD3 improved the resistance of locusts to both specialist and generalist fungal pathogens (wide host range) but had no effect on the fungal resistance of other insects, including Spodoptera frugiperda and Galleria mellonella. Hydrophobins extracted from the generalist fungal pathogens M. anisopliae and Beauveria bassiana had no effect on the resistance of locusts to fungal infection. Thus, the host locust has evolved to recognize the conidial hydrophobin of its specialist fungal pathogen, whereas conidial hydrophobins from generalist fungi are able to evade recognition. Our results distinguish the immunogenic potential of conidial hydrophobins between specialist and generalist fungi.

9.
J Craniofac Surg ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33055566

RESUMO

PURPOSE: The aim of this work is to demonstrate the outcomes of endonasal dacryocystorhinostomy (En-DCR) with anterior ethmoid sinus mucosal and posterior lacrimal sac flap anastomosing in patients with previous failed DCR. METHODS: The clinical data of patients who suffered from recurrent epiphora after failed DCR between September 2014 and March 2018 were reviewed retrospectively. Among them, those who received the second En-DCR procedure were enrolled in this study. During the surgery, anterior ethmoidectomy was performed. Posterior lacrimal sac flap was apposed closely to the mucosal of anterior ethmoid sinus instead of nasal flap at end of the surgery. Patients were followed up more than 12 months were included, the success rate and complications were recorded. RESULTS: Sixty-one eyes of 61 patients were enrolled in the study. The success rate of our modified En-DCR was 83.6% (51/61). Among 10 eyes with postoperative obstruction, 4 eyes caused by granuloma, 2 eyes caused by scar synechia, 2 eyes caused by membranous obstruction, and 2 eyes caused by common canalicular stenosis. No serious complications such as orbital fat prolapse, cerebrospinal fluid leak, sinusitis, or visual impairment were occurred in this study. CONCLUSION: Endoscopic approach with anterior ethmoid sinus mucosal and posterior lacrimal sac flap anastomosing is a good choice for patients with recurrent epiphora after previous failed DCR.

10.
Acta Diabetol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064205

RESUMO

AIMS: To determine the relationship between plasma levels of trimethylamine-N-oxide (TMAO) and odds of diabetic retinopathy (DR). METHODS: A cross-sectional study was conducted. Blood samples were obtained from 122 type 2 diabetes mellitus (T2DM) patients with or without DR. Multivariable logistic regression analyses were performed to identify the association between plasma TMAO and DR. The diagnostic value of plasma TMAO was assessed by the area under the receiver operating characteristic curve (AUROC) and integrated discrimination improvement (IDI). RESULTS: In the T2DM patients, plasma levels of TMAO were significantly higher in patients with DR compared with those without DR (P = 0.001). As logarithmic (ln) transformation of TMAO increased per standard deviation (SD), there was higher probability to have DR [odds ratio (OR) = 2.31; P = 0.005]. As ln-transformed TMAO increased per SD, the severity of DR was more likely to get worse (OR = 2.05; P = 0.004). In the diagnostic model, the addition of TMAO contributed to the improvement in AUROC from 0.646 to 0.734 (P = 0.043), and the IDI was 10.7% (P < 0.001). CONCLUSION: Elevated levels of plasma TMAO were associated with higher odds and worse severity of DR in T2DM patients, and further investigation is required for the causality of this association.

11.
Nat Immunol ; 21(11): 1384-1396, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32989327

RESUMO

T follicular helper (TFH) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives the initiation of their developmental program remains unclear. Studies suggest that a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest TFH cell-fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized that tonic signaling influences early TFH cell development. Here, two murine TCR-transgenic CD4+ T cells, LLO56 and LLO118, which recognize the same antigenic peptide presented on major histocompatibility complex molecules but experience disparate strengths of tonic signaling, revealed low tonic signaling promotes TFH cell differentiation. Polyclonal T cells paralleled these findings, with naive Nur77 expression distinguishing TFH cell potential. Two mouse lines were also generated to both increase and decrease tonic signaling strength, directly establishing an inverse relationship between tonic signaling strength and TFH cell development. Our findings elucidate a central role for tonic TCR signaling in early TFH cell-lineage decisions.

12.
World J Surg ; 44(12): 4142-4148, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918103

RESUMO

BACKGROUND: Lymph node metastasis (LNM) often occurs in papillary thyroid carcinoma (PTC); the efficacy of ultrasound for predicting high-volume lymph node metastases (LNMs) in patients with PTC remains unexplored. METHODS: The medical records of 2073 consecutive PTC patients were reviewed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to evaluate the efficacy of ultrasound. Risk factors for LNM/high-volume LNMs and lymph node involvement on ultrasound (usLNM) were identified by univariate and multivariate analyses. RESULTS: Of all the patients, 936 (45.2%) patients had LNMs, and 254 (12.3%) patients had high-volume LNMs. The sensitivity of ultrasound for detecting LNM/high-volume LNMs was 27.9% and 63.8%, respectively; the specificity was 93.1% and 90.3%, respectively. The NPV for ultrasound in detecting high-volume LNMs was 94.7%. In multivariate analysis, male sex (OR = 2.108, p < 0.001), tumor diameter > 1.0 cm (OR = 2.304, p < 0.001) and usLNM (+) (OR = 12.553, p < 0.001) were independent clinical risk factors for high-volume LNMs. Tumor diameter > 1 cm (OR = 3.036, p < 0.001) and male sex (OR = 1.642, p < 0.001) were independent clinical risk factors for usLNM; a skilled sonographer (OR = 1.121, p = 0.358) was not significantly associated with usLNM. CONCLUSIONS: Lymph node involvement found by ultrasound has great predictive value for high-volume LNMs; the NPV is very high for patients without lymph node involvement on ultrasound. The ultrasound results do not appear to be influenced by the experience of the sonographer.

13.
Org Lett ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936655

RESUMO

Difunctionalization of alkenes is a valuable tool for the synthesis of complicated compounds from simple precursors. Herein, a feasible method for the construction of ß-trifluoromethyl-α-substituted alcohols under visible-light-induced metal-free conditions is described. This catalytic system exhibits mild reaction conditions and good compatibility of functional groups. Trifluoromethyl and alcohols are valuable structural motifs due to their unique biological properties, and this work shows the potential application in the realm of pharmacy and organic synthesis.

14.
Curr Gene Ther ; 20(2): 127-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32951572

RESUMO

Suppression of TP53 function is nearly ubiquitous in human cancers, and a significant fraction of cancers have mutations in the TP53 gene itself. Therefore, the wild-type TP53 gene has become an important target gene for transformation research of cancer gene therapy. In 2003, the first anti-tumor gene therapy drug rAd-p53 (recombinant human p53 adenovirus), trade name Gendicine™, was approved by the China Food and Drug Administration (CFDA) for treatment of head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy. The recombinant human TP53 gene is delivered into cancer cells by an adenovirus vector constructed to express the functional p53 protein. Although the only currently approved used of Gendicine is in combination with radiotherapy for treatment of HNSCC, clinical studies have been carried out for more than 20 other applications of Gendicine in treating cancer, including treatment of advanced lung cancer, advanced liver cancer, malignant gynecological tumors, and soft tissue sarcomas. Currently more than 30,000 patients have been treated with Gendicine. This review provides an overview of the clinical applications of Gendicine in China. We summarize a total of 48 studies with 2,561 patients with solid tumors, including 34 controlled clinical studies and 14 open clinical studies, i.e., clinical studies without a control group. There are 11 studies for head and neck cancer, 10 for liver cancer, 6 for malignant gynecological tumors, 4 for non-small cell lung cancer, 4 for soft tissue sarcoma, 4 for malignant effusion, 2 for gastrointestinal tumors, and 7 for other types of cancer. In all the reported clinical studies, the most common side effect was self-limited fever. Intratumoral injection and intra-arterial infusion were the most common routes of administration. Overall, Gendicine combined with chemotherapy, radiotherapy, or other conventional treatment regimens demonstrated significantly higher response rates compared to standard therapies alone. Some of the published studies also showed that Gendicine combination regimens demonstrated longer progression-free survival times than conventional treatments alone. To date, Gendicine has been clinically used in China for treatment of cancers other than HNSCC for more than ten years, mainly for patients with advanced or unresectable malignant tumors. However, the establishment of standard treatment regimens using TP53 gene therapy is still needed in order to advance its use in clinical practice.

15.
Int Heart J ; 61(5): 936-943, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879265

RESUMO

On the basis of radiofrequency ablation of atrial fibrillation (AF), some studies suggested that early recurrences of atrial tachyarrhythmia (ERATs) were associated with late AF recurrence (LAFR), and some also suspected and challenged the current recommended 90 day blanking period. We aim to evaluate the impact of ERAT on long-term success and to determine the optimum blanking period after AF ablation using second-generation cryoballoon (sg-CB). From August 2016 to October 2018, 369 consecutive patients who successfully underwent initial AF ablation using sg-CB at the Fuwai Hospital were finally enrolled. All patients were followed up no less than 12 months. Receiver operating characteristic curve analysis was used to determine the optimum blanking period after AF ablation. There were 62 (16.8%) who experienced ERAT. After a median follow-up of 615 days, 74.5% were free of LAFR after the 90 day blanking period. Incidence of freedom from LAFR during the long-term follow-up was markedly lower in patients with ERAT than in those without ERAT (27.4% versus 84.0%; log-rank P < 0.001). Furthermore, only ERAT (HR 8.579; 95% CI 5.604-13.133; P < 0.001) was significantly associated with an increased risk of LAFR after adjusting for other factors. The optimum cut-off time point for the blanking period was 21.5 days (sensitivity: 71.1%, specificity: 94.1%). In conclusion, ERAT was an independent predictor of LAFR after AF ablation using sg-CB. Based on our findings, blanking period was advised to be shorten to 21.5 days or about 3 weeks instead of 90 days after CB ablation.


Assuntos
Fibrilação Atrial/cirurgia , Criocirurgia , Veias Pulmonares/cirurgia , Recidiva , Falha de Tratamento , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
16.
Cardiology ; 145(11): 710-719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841940

RESUMO

BACKGROUND: There are several electrocardiographic algorithms to predict the origin of idiopathic outflow tract ventricular arrhythmias (OT-VAs). This study aimed to develop a more accurate and efficient stepwise electrocardiographic algorithm to discriminate left ventricular outflow tract (LVOT) from right ventricular outflow tract (RVOT) origin. METHODS AND RESULTS: We analyzed 12-lead electrocardiographic characteristics of 173 consecutive OT-VAs patients who underwent successful radiofrequency catheter ablation in the RVOT (n = 124) or LVOT (n = 49). Based on the areas under the receiver operating characteristic curves, the combination of transitional zone (TZ) index <0 and V2S/V3R index ≤1.5 exhibited 93.5% sensitivity, 85.9% specificity, and 87.3% accuracy. A further analysis was performed in the 71 OT-VAs with a V3-lead precordial transition. The sensitivity, specificity, and accuracy of the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms were 91.7, 83.1, and 85.9%, respectively. In the prospective evaluation, the combination of TZ index and V2S/V3R index could identify the correct origin sites with 91.2% accuracy in the overall analysis, and the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms exhibited 94% accuracy in V3-lead precordial transition. CONCLUSIONS: The combination of TZ index <0 and V2S/V3R index ≤1.5 is a simple and efficient stepwise electrocardiographic algorithm for predicting LVOT origin. For the OT-VAs with a V3-lead precordial transition, the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms would be a better choice.

17.
Reprod Domest Anim ; 55(11): 1554-1564, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32815612

RESUMO

The relationship between the conceptus and the maternal uterine environment is crucial for the successful establishment and maintenance of pregnancy in cattle. Gene expression analysis of the conceptus and maternal reproductive tissues is a favourable method to assess the embryonic maternal interaction. The reliability of the commonly used method reverse transcription-quantitative polymerase chain reaction (RT-qPCR) depends on proper normalization to stable reference genes (RGs). The objective of this study was to determine the expression stability of 10 potential RGs in maternal reproductive tissues and foetal tissues, and to analyse the effect of RG selection on the calculation of the relative expression of target genes. The expression stability of 10 potential RGs was analysed in eight different tissues from three pregnant dairy cows. Three programs-GeNorm, NormFinder and Bestkeeper-were used to identify the best RGs. According to all three programs, the most stable RG was CNOT11, whereas the least stable RGs were GAPDH and HPRT1. GeNorm analysis showed that a combination of five RGs (SDHA, PPIA, CNOT11, RPS9 and RPL19) was necessary for appropriate data normalization. However, NormFinder analysis indicated that the combination of CNOT11 and PPIA was the most suitable. When target genes were normalized to these RGs, the relative expression of the Radical S-adenosyl methionine domain containing 2 gene was not affected by the choice of RGs, whereas a large difference was observed in the expression profile of the Nuclear erythroid2-related factor 2 gene between the most stable and least stable RGs. The results indicate that careful selection of RGs is crucial under different conditions, especially for target genes with relatively small fold changes. Furthermore, the results provide useful information for the selection of RGs for evaluating genes affecting bovine reproduction.

18.
Curr Gene Ther ; 20(4): 313-320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851960

RESUMO

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is one of the most common ovarian epithelial carcinomas. It is highly invasive, easily recurs after systemic treatment, and has a poor prognosis. Despite many new chemotherapeutic drugs and trials of combinations of different regimens that have been used in treatment attempts, there has been no meaningful progress in the treatment of HGSOC. With the development of gene sequencing technology, gene therapy has become a new direction for tumors treatment. It is reported that the P53 has a very high mutation rate in HGSOC, which provides a theoretical basis for the application of gene therapy in HGSOC patients. Recombinant human p53 adenovirus injection (rAd-p53) is the world's first approved oncology gene therapy drug. CASE REPORT: In this article, we retrospectively analyzed 4 cases of HGSOC patients treated with rAdp53. Three of them were recurrent ovarian cancer, and one was the initial treatment. The treatment method was to apply recombinant human p53 adenovirus injection (rAd-p53) to the lesions for local injection, 72 hours later, the lesions were injected with bleomycin or fluorouracil, and systemic intravenous chemotherapy was performed simultaneously. After rAd-p53 treatment, one of the three relapsed ovarian cancers achieved complete remission(CR), one achieved partial remission (PR), and one was stable disease (SD); the treatment-naive patient was operated after rAd-p53 combined with neoadjuvant chemotherapy and achieved pathological CR. Under the action of various mechanisms of P53, the subsequent tumor treatment showed the characteristics of slow tumor progression, no ascites, and local recurrence. As of the end of follow-up, the OS of 4 patients was 71-120 months. CONCLUSION: Through the remarkable efficacy of these 4 cases, we can see that the application of rAdp53 combined with chemotherapy can effectively control tumor lesions, prolong the survival time of patients, improve the quality of life of patients, which provide valuable experiences for rAd-p53 treatment in ovarian cancer, promote the further development and progress of gene therapy in this field.

19.
Mil Med Res ; 7(1): 38, 2020 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799919

RESUMO

BACKGROUND: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). METHODS: We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. RESULTS: In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001). CONCLUSION: Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.

20.
Nature ; 585(7824): E5, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32826961

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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