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1.
Zhongguo Zhong Yao Za Zhi ; 46(1): 15-23, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645046

RESUMO

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

2.
J Orthop Surg Res ; 16(1): 157, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627145

RESUMO

BACKGROUND: Adult developmental dysplasia of the hip is an untreated congenital hip dysplasia that results in adult hip pain. One of the usual and effective methods for the treatment of this condition is periacetabular osteotomy. However, which approach is better between the modified S-P and the I-I approaches is still unclear and controversial. METHOD AND MATERIALS: We retrospectively assessed our experience with the modified S-P and the I-I approaches by inquiring and evaluating intraoperative blood loss, postoperative radiographic material, postoperative function of the hip, and related complications from July 2014 to January 2019. RESULTS: A total of 61 patients with adult developmental dysplasia of the hip were enrolled, and 33 patients were divided into a modified S-P group and 28 patients were divided into I-I group. The operation time and blood loss of group I-I were higher than that of group modified S-P. Other clinical and radiographic indexes showed no statistical significance between group the modified S-P and I-I groups. CONCLUSION: There is no significant difference in the improvement of the function of the hip at the post-operation stage, but group I-I may require more operation time and blood loss at the intra-operation stage.

3.
Transbound Emerg Dis ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559368

RESUMO

The variety and widespread of coronavirus in natural reservoir animals is likely to cause epidemics via interspecific transmission, which has attracted much attention due to frequent coronavirus epidemics in recent decades. Birds are natural reservoir of various viruses, but the existence of coronaviruses in wild birds in central China has been barely studied. Some bird coronaviruses belongs to the genus of Deltacoronavirus. To explore the diversity of bird deltacoronaviruses in central China, we tested fecal samples from 415 wild birds in Hunan Province, China. By RT-PCR detection, we identified eight samples positive for deltacoronaviruses which were all from common magpies, and in four of them, we successfully amplified complete deltacoronavirus genomes distinct from currently known deltacoronavirus, indicating four novel deltacoronavirus stains (HNU1-1, HNU1-2, HNU2 and HNU3) . Comparative analysis on the four genomic sequences showed that these novel magpie deltacoronaviruses shared three different S genes among which the S genes of HNU1-1 and HNU1-2 showed 93.8% amino acid (aa) identity to that of thrush coronavirus HKU12, HNU2 S showed 71.9% aa identity to that of White-eye coronavirus HKU16, and HKU3 S showed 72.4% aa identity to that of sparrow coronavirus HKU17. Recombination analysis showed that frequent recombination events of the S genes occurred among these deltacoronavirus strains. Two novel putative cleavage sites separating the nonstructural proteins in the HNU coronaviruses were found. Bayesian phylogeographic analysis showed that the south coast of China might be a potential origin of bird deltacoronaviruses existing in inland China. In summary, these results suggest that common magpie in China carries diverse deltacoronaviruses with novel genomic features, indicating an important source of environmental coronaviruses closed to human communities, which may provide key information for prevention and control of future coronavirus epidemics.

4.
Trials ; 22(1): 121, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549133

RESUMO

BACKGROUND: Natural orifice specimen extraction surgery for colorectal cancer has been introduced in order to reduce the abdominal incision, demonstrating major development potential in minimally invasive surgery. We are conducting this randomized controlled trial to assess whether robotic NOSES is non-inferior to traditional robotic-assisted surgery for patients with colorectal cancer in terms of primary and secondary outcomes. METHOD/DESIGN: Accordingly, a prospective, open-label, randomized controlled, parallel-group, multicenter, and non-inferiority trial will be conducted to discuss the safety and efficacy of robotic natural orifice extraction surgery compared to traditional robotic-assisted surgery. Here, 550 estimated participants will be enrolled to have 80% power to detect differences with a one-sided significance level of 0.025 in consideration of the non-inferiority margin of 10%. The primary outcome is the incidence of surgical complications, which will be classified using the Clavien-Dindo system. DISCUSSION: This trial is expected to reveal whether robotic NOSES is non-inferior to traditional robotic-assisted surgery, which is of great significance in regard to the development of robotic NOSES for patients with colorectal cancer in the minimally invasive era. Furthermore, robotic NOSES is expected to exhibit superiority to traditional robotic-assisted surgery in terms of both primary and secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04230772 . Registered on January 15, 2020.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33587710

RESUMO

In this article, a novel reinforcement learning (RL) method is developed to solve the optimal tracking control problem of unknown nonlinear multiagent systems (MASs). Different from the representative RL-based optimal control algorithms, an internal reinforce Q-learning (IrQ-L) method is proposed, in which an internal reinforce reward (IRR) function is introduced for each agent to improve its capability of receiving more long-term information from the local environment. In the IrQL designs, a Q-function is defined on the basis of IRR function and an iterative IrQL algorithm is developed to learn optimally distributed control scheme, followed by the rigorous convergence and stability analysis. Furthermore, a distributed online learning framework, namely, reinforce-critic-actor neural networks, is established in the implementation of the proposed approach, which is aimed at estimating the IRR function, the Q-function, and the optimal control scheme, respectively. The implemented procedure is designed in a data-driven way without needing knowledge of the system dynamics. Finally, simulations and comparison results with the classical method are given to demonstrate the effectiveness of the proposed tracking control method.

6.
Cancers (Basel) ; 13(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450815

RESUMO

Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of CTC-clusters. In 227 longitudinally collected blood samples from 64 mCRPC patients, CTCs and CTC-clusters were enumerated using the CellSearch platform. The associations of CTC and CTC-cluster counts with progression-free survival (PFS) and overall survival (OS), individually and jointly, were evaluated by Cox models. CTCs and CTC-clusters were detected in 24 (37.5%) and 8 (12.5%) of 64 baseline samples, and in 119 (52.4%) and 27 (11.9%) of 227 longitudinal samples, respectively. CTC counts were associated with both PFS and OS, but CTC-clusters were only independently associated with an increased risk of death. Among patients with unfavorable CTCs (≥5), the presence of CTC-clusters signified a worse survival (log-rank p = 0.0185). mCRPC patients with both unfavorable CTCs and CTC-clusters had the highest risk for death (adjusted hazard ratio 19.84, p = 0.0072), as compared to those with <5 CTCs. Analyses using longitudinal data yielded similar results. In conclusion, CTC-clusters provided additional prognostic information for further stratifying death risk among patients with unfavorable CTCs.

7.
Sci Rep ; 11(1): 1868, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479333

RESUMO

The variant virulent porcine epidemic diarrhea virus (PEDV) strain (YN15) can cause severe porcine epidemic diarrhea (PED); however, the attenuated vaccine-like PEDV strain (YN144) can induce immunity in piglets. To investigate the differences in pathogenesis and epigenetic mechanisms between the two strains, differential expression and correlation analyses of the microRNA (miRNA) and mRNA in swine testicular (ST) cells infected with YN15, YN144, and mock were performed on three comparison groups (YN15 vs Control, YN144 vs Control, and YN15 vs YN144). The mRNA and miRNA expression profiles were obtained using next-generation sequencing (NGS), and the differentially expressed (DE) (p-value < 0.05) mRNA and miRNA were obtained using DESeq R package. mRNAs targeted by DE miRNAs were predicted using the miRanda algortithm. 8039, 8631 and 3310 DE mRNAs, and 36, 36, and 22 DE miRNAs were identified in the three comparison groups, respectively. 14,140, 15,367 and 3771 DE miRNA-mRNA (targeted by DE miRNAs) interaction pairs with negatively correlated expression patterns were identified, and interaction networks were constructed using Cytoscape. Six DE miRNAs and six DE mRNAs were randomly selected to verify the sequencing data by real-time relative quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on bioinformatics analysis, we discovered the differences were mostly involved in host immune responses and viral pathogenicity, including NF-κB signaling pathway and bacterial invasion of epithelial cells, etc. This is the first comprehensive comparison of DE miRNA-mRNA pairs in YN15 and YN144 infection in vitro, which could provide novel strategies for the prevention and control of PED.

8.
Huan Jing Ke Xue ; 42(1): 75-87, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372459

RESUMO

From June to August 2018, a 1-hr resolution concentration dataset of ozone and its gaseous precursors (volatile organic compounds(VOCs) and NOx), and meteorological parameters were synchronously monitored by online instruments of the Nankai University Air Quality Research Supersite. The relationships and variation characteristics between ozone and its precursors were analyzed. According to the photochemical age, the initial concentrations of VOCs were calculated, and the photochemical loss of the concentration of VOCs during the daytime (06:00-24:00) was corrected. The initial and directly monitored concentrations of VOCs were incorporated into the PMF model for source apportionment. The results indicated that the mean concentration of O3 in Tianjin in summer was (41.3±25.7)×10-9, while that of VOCs was (13.9±12.3)×10-9. The average concentration of alkane (7.0±6.8)×10-9 was clearly higher than that of other VOC species. The species with high concentrations of alkanes were propane and ethane, accounting for 47% of the total alkane concentration. The average ozone formation potential (OFP) in summer was 52.1×10-9, and the OFP value of alkene was the highest and its contribution reached 57%. During the daytime, alkene loss accounted for 75% of the total VOC loss. The major sources of VOCs that were calculated based on the initial concentration data were the chemical industry and solvent usage (25%), automobile exhaust (22%), combustion source (19%), LPG/NG (19%), and gasoline volatilization (15%), respectively. Compared with the apportionment results based on directly monitored concentrations, the contribution of the chemical industry and solvent usage decreased by 4%, while automobile exhaust decreased by 5%. By combining the results of PMF apportionment and the OFP model to analyze the relative contributions of emission sources to ozone formation, and we found that the highest contribution source of ozone was the chemical industry and solvent usage (26%) in summer. Compared with the analysis results based on the directly monitored concentrations, the OFP values of the chemical industry and solvent usage decreased by 7%, while that of NG/LPG apparently decreased by 13%.

9.
Dev Comp Immunol ; 115: 103880, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33022353

RESUMO

IκB kinase α (IKKα) is a vital component of the IKK complex, which is involved in innate immune response, inflammation, cell death and proliferation. Although the functional characteristics of IKKα have been extensively studied in mammals and fish, the roles of IKKα in avian remain largely unknown. In this study, we cloned and characterized the duck IKKα (duIKKα) gene for the first time. DuIKKα encoded a protein of 757 amino acid residues and showed high sequence identities with the goose IKKα. The duIKKα was expressed in all tested tissues, and a relatively high expression of duIKKα mRNA was detected in liver and heart. Overexpression of duIKKα dramatically increased NF-κB activity and induced the expression of duck cytokines IFN-ß, IL-1ß, IL-6, IL-8 and RANTES in DEFs. Knockdown of duIKKα by small interfering RNA significantly decreased LPS-, poly(I:C)-, poly(dA:dT)-, duck enteritis virus (DEV)-, or duck Tembusu virus (DTMUV)-induced NF-κB activation. Moreover, duIKKα exhibited antiviral activity against DTMUV infection. These findings provide important insights into the roles of duIKKα in avian innate immunity.

10.
Dev Comp Immunol ; 115: 103906, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33127560

RESUMO

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that caused severe egg drop syndrome in laying ducks in China since 2010, leading to massive economic losses to the duck industry. Although the DTMUV E protein is considered to be critical in inducing the protective immune response, the functional epitopes within this protein remain largely unknown. In the present study, we isolated a DTMUV neutralizing monoclonal antibody (mAb) 3B8 from DTMUV E-immunized mice. Epitope mapping showed that mAb 3B8 recognized a novel linear epitope FSCLGMQNR located on the extreme N-terminal of the domain I (EDI) of E protein. Sequence alignment and Western blot analyses showed that the epitope is greatly conserved with high DTMUV-specificity. Moreover, upon cloning the heavy and light chain variable region sequences of mAb 3B8, we prepared the single-chain variable antibody fragment (scFv) 3B8 by connecting the two chains via a flexible peptide linker. The recombinant scFv 3B8 exhibited antiviral activity against DTMUV infection in vitro and in vivo. Our results provide valuable implications for the development of DTMUV vaccines and therapeutics.

11.
Medicine (Baltimore) ; 99(50): e23613, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327332

RESUMO

RATIONALE: Rectal atresia caused by necrotizing enterocolitis (NEC) is a serious and rare complication in children. Magnetic compression anastomosis (MCA) has been effectively applied in children with congenital oesophageal atresia and biliary atresia. Herein, we reported a case of successfully application of MCA in an infant with rectal atresia following NEC. PATIENT CONCERNS: A 30 weeks premature birth female fetal infant was transferred to our neonatal intensive care unit due to premature delivery, low birth weight, and neonatal respiratory distress. On postpartum day 11, the infant developed abdominal distension and mucosanguineous feces. This infant was then clinically diagnosed as NEC. She underwent anesthesia and intestinal fistula operation on postpartum day 11 because of NEC. DIAGNOSIS: After 3 months, radiographic examination revealed rectal atresia and stricture. INTERVENTIONS: This infant was successfully treated with MCA following a cecum-rectal anastomosis and ileocecal valve was reserved. OUTCOMES: On postoperative day 9, she passed the 2 magnets per rectum. In addition, there were no difficult defecation or fecal incontinence or other short-term complications. After the 7-month follow-up, the patient had an excellent clinical outcome. LESSONS: MCA is a feasible and effective method for treating rectal atresia in infants.


Assuntos
Enterocolite Necrosante/diagnóstico , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Atresia Intestinal/diagnóstico , Reto/anormalidades , Anastomose Cirúrgica , Diagnóstico Diferencial , Enterocolite Necrosante/complicações , Enterocolite Necrosante/cirurgia , Feminino , Humanos , Recém-Nascido , Atresia Intestinal/complicações , Atresia Intestinal/diagnóstico por imagem , Atresia Intestinal/cirurgia , Imãs
12.
Ann Transl Med ; 8(20): 1292, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209872

RESUMO

Background: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear. Methods: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics. Results: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%. Conclusions: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC.

13.
Front Cell Dev Biol ; 8: 586109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117812

RESUMO

The archetypal store-operated Ca2+ channels (SOCs), Orai1, which are stimulated by the endo/sarcoplasmic reticulum (ER/SR) Ca2+ sensor stromal interaction molecule 1 (STIM1) upon Ca2+ store depletion is traditionally viewed as instrumental for the function of non-excitable cells. In the recent years, expression and function of Orai1 have gained recognition in excitable cardiomyocytes, albeit controversial. Even if its cardiac physiological role in adult is still elusive and needs to be clarified, Orai1 contribution in cardiac diseases such as cardiac hypertrophy and heart failure (HF) is increasingly recognized. The present review surveys our current arising knowledge on the new role of Orai1 channels in the heart and debates on its participation to cardiac hypertrophy and HF.

14.
Medicine (Baltimore) ; 99(42): e22472, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080683

RESUMO

RATIONALE: Neonatal long-gap esophageal atresia (LGEA) with tracheoesophageal fistula (TEF) is an uncommon but serious congenital malformation of the esophagus in newborns, and it remains challenging for pediatric surgeons. Magnetic compress has been shown to be effective for the treatment of LGEA in children and adults. However, the implementation of this unique technique for neonatal LGEA has not been evaluated. PATIENT CONCERNS: A female infant was born at 37 weeks of gestation. Prenatal ultrasound imaging revealed signs of esophageal atresia, including the absence of the gastric bubble and polyhydramnios. DIAGNOSES: A diagnosis of LGEA with TEF was confirmed at birth by contrast X-ray. INTERVENTIONS: She was treated with magnetic compression anastomosis (MCA) following an esophago-esophagostomy. Two magnetic rings were customized, and the MCA was conducted during the same stage surgery of ligating the TEF. Under the magnetic force, the 2 magnet rings pulled along the gastric tube to achieve anastomosis. The postoperative permanent suction of these 2 pouches was instituted, and spontaneous growth was awaited. Magnet removal was performed at 36 days, and enteral nutrition was continued via a gastric tube for 4 weeks at post-operation. OUTCOMES: The upper gastrointestinal contrast confirmed the anastomotic patency perfectly after 3 months. The patient was followed up for 18 months, and exhibited durable esophageal patency without dysphagia. LESSONS: These results suggest that MCA is feasible and effective for treating LGEA in infants.


Assuntos
Anastomose Cirúrgica/métodos , Atresia Esofágica/cirurgia , Fístula Traqueoesofágica/cirurgia , Atresia Esofágica/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Magnetismo , Fístula Traqueoesofágica/diagnóstico por imagem
15.
Eur J Pharm Sci ; : 105631, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33115675

RESUMO

BACKGROUND: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir acid and favipiravir in COVID-19 patients. METHODS: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). RESULTS: Baloxavir acid showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 µM comparable to arbidol and lopinavir, but favipiravir didn't demonstrate significant antiviral activity up to 100 µM. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir marboxil, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. One of the limitations of this study is the time from symptom onset to randomization, especially in the baloxavir marboxil and control groups, which is higher than the favipiravir group. CONCLUSIONS: Our findings could not prove a benefit of addition of either baloxavir marboxil or favipiravir under the trial dosages to the existing standard treatment.

16.
J Cardiothorac Surg ; 15(1): 233, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873341

RESUMO

BACKGROUND: Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that was usually misdiagnosed as chronic pulmonary thromboembolism. CASE PRESENTATION: We previously reported a solitary fibrous tumor in the pulmonary artery presented with acute pulmonary embolism, which was identified by 99mTc-Galacto-RGD2 imaging. However, this patient had a recurrence in situ two-year after surgery, post-operative pathology revealed pulmonary artery intimal sarcoma. At one-year post-operation, 18F-FDG PET/CT was performed for exclusion of tumor metastasis, which showed FDG avid lesion in the T5, T10, and L5 vertebral bodies, as well as in bilateral ilium and right ischium. CONCLUSIONS: This is the first longitudinal observation of a solitary fibrous tumor (SFT) development into a pulmonary artery intimal sarcoma (PAIS) and presented with multiple bone metastases.

17.
AAPS PharmSciTech ; 21(7): 253, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32888086

RESUMO

We developed a pH-triggered in situ gel (ISG) for ocular delivery of vinpocetine to achieve systemic absorption and a brain-targeting effect in rats. Carbopol acted as a gelling agent combined with hydroxypropyl methylcellulose (HPMC) as a viscosity-enhancing agent. The concentration of Carbopol (0.2%, w/v) and HPMC (1.5%, w/v) was optimized for the ISG system. The optimized formulation was evaluated for studies on release in vitro, rheology, differential scanning calorimetry, ocular irritation, residence time, and in vivo pharmacokinetics. The vinpocetine ISG stayed longer in rabbit eyes than vinpocetine ointment. In vivo pharmacokinetics showed that compared with vinpocetine ointment, vinpocetine ISG attained a peak plasma concentration and area under the curve that was 1-2 folds greater in rat plasma. The Drug Targeting Index (DTI) was 1.06 and 1.26 for vinpocetine ointment and vinpocetine ISG, respectively, after ocular administration, showing that vinpocetine ISG had better distribution in rat brain. These results revealed that a pH-triggered ISG system via ocular administration could be an alternative approach compared with traditional ophthalmic formulations.

18.
Epigenet Insights ; 13: 2516865720930701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964196

RESUMO

Background: How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites. Methods: Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC. Results: Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin (PCDH) gene clusters were associated with gene expression of PCDH in F2 cord blood. Conclusions: Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.

19.
Cytokine ; 136: 155287, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32950027

RESUMO

Haemophilus parasuis induces severe acute systemic infection in pigs, characterized by fibrinous polyserositis, polyarthritis and meningitis. Our previous study demonstrated that H. parasuis induced the activation of p38 mitogen-activated protein kinase (MAPK) pathway, increasing the expression of proinflammatory genes and mediating H. parasuis-induced inflammation. Moreover, Wnt/ß-catenin signaling activation induced by H. parasuis disrupts the adherens junction between epithelial cells and initiates the epithelial-mesenchymal transition (EMT). In the present study, p38 MAPK was found to be involved in the accumulation of nuclear location of ß-catenin during H. parasuis infection in PK-15 and NPTr cells, via modulating the expression of dickkofp-1 (DKK-1), a negative regulator of Wnt/ß-catenin signaling. We generated DKK-1 knockout cell lines by CRISPR/Cas9-mediated genome editing in PK-15 and NPTr cells, and found that knockout of DKK-1 led to the dysfunction of p38 MAPK in regulating Wnt/ß-catenin signaling activity in H. parasuis-infected cells. Furthermore, p38 MAPK activity was independent of the activation of Wnt/ß-catenin signaling during H. parasuis infection. This is the first study to explore the crosstalk between p38 MAPK and Wnt/ß-catenin signaling during H. parasuis infection. It provides a more comprehensive view of intracellular signaling pathways during pathogenic bacteria-induced acute inflammation.

20.
Sci Rep ; 10(1): 12848, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32733103

RESUMO

Robotic rectal cancer resection with natural orifice extraction is a recently developed minimally invasive surgery used in the treatment of patients with rectal cancer. However, its safety and feasibility remain undiscussed and controversial. This study reported the clinical outcomes and prognostic factors pertaining to traditional robotic assisted rectal cancer resection alone against that of robotic rectal cancer resection with natural orifice extraction to provide a discussion on this issue. 49 patients who underwent robotic rectal cancer resection with natural orifice extraction and 49 matched patients who underwent conventional robotic assisted rectal cancer resection were systematically analyzed in this study. Regarding the baseline characteristics, after matching, no significant differences were observed between the natural orifice specimen extraction (NOSE) group and the robotic assisted rectal cancer resection (RARC) group. Patients in the NOSE group had a reduced visual analog scale (p < 0.001), passed flatus more quickly (p = 0.002) and suffered less surgical stress than those in the RARC group. Moreover, 4 complications were observed in the NOSE group and 7 complications in the RARC group with no significant difference (p = 0.337) in terms of complications. The two groups had a similar survival outcomes, where the 3-year overall survival (p = 0.738) and 3-year progression-free survival (p = 0.986) were all comparable between the two groups. Histological differentiation and T stage could be regarded as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. Robotic rectal cancer resection with natural orifice extraction is a safe and feasible minimally invasive surgery for patients suffering from rectal cancer as it encompasses considerable several advantages. Histological differentiation and T stage may serve as independent prognostic factors for 3-year overall survival and 3-year progression-free survival.

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