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1.
Scand J Gastroenterol ; : 1-8, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962533

RESUMO

OBJECTIVES: The efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease (CD) has not been well studied. We aimed to evaluate the efficacy of infliximab in these patients. MATERIALS AND METHODS: This was a retrospective study of all consecutive treatment-naïve patients with newly diagnosed CD with small bowel stricture who started regular infliximab therapy in Nanfang Hospital between January 2015 and December 2019. An effective infliximab therapy was defined as infliximab continuation without the use of steroids, new biologics, endoscopic interventions or intestinal surgery. RESULTS: Seventy-nine patients were included. After a median 38 months follow-up, an effective infliximab therapy was achieved in 37 patients. Long diagnostic delay (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.19-0.78; p= .008), pre-stenotic dilatation (HR 0.17, 95%CI 0.09-0.35; p < .001), long segmental stricture (HR 0.20, 95%CI 0.10-0.41; p < .001), and penetrating disease (HR 0.22, 95%CI 0.10-0.49; p < .001) were negatively correlated with an effective infliximab therapy. CONCLUSIONS: Infliximab is effective in nearly 50% of treatment-naïve patients with CD with small bowel stricture, and an effective therapy is more likely to be achieved in patients without long diagnostic delay, pre-stenotic dilatation, long segmental stricture or penetrating disease.

2.
J Food Biochem ; : e13722, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33855723

RESUMO

This study aimed to examine the role of Zizyphus jujuba cv. Muzao polysaccharides (ZJPs) in protecting intestinal barrier function and the survival of septic mice. The sepsis mouse model was generated through cecal ligation and puncture (CLP) to observe the effect of ZJPs on the function of the intestinal barrier in the context of sepsis. We observed the clinical symptoms and survival time of the mice and evaluated serum inflammatory cytokines, intestinal pathological changes and intestinal permeability. Moreover, tight junction (TJ) proteins and apoptosis-associated proteins in intestinal tissue were examined. Finally, TLR4/NF-κB pathway-related proteins were measured in all groups. The results showed that pretreatment with ZJPs improved clinical and histological scores and reduced intestinal barrier permeability, and the levels of proinflammatory factors were decreased. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice by ZJPs pretreatment. The current study provides evidence that ZJPs have the potential to protect intestinal barrier function and improve the survival of septic mice via the attenuation of TLR4/NF-κB inflammatory signaling. PRACTICAL APPLICATIONS: This study reports the potential protective effect of ZJPs against cecal ligation and puncture (CLP)-induced sepsis. Our data reveal that CLP induced damage to the gut mucosal barrier, inflammation, and apoptosis in intestinal tissues. However, pretreatment with ZJPs improved clinical and histological scores, reduced intestinal barrier permeability, and decreased the levels of proinflammatory factors in mice. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice after ZJPs pretreatment. These findings provide evidence that pretreatment with ZJPs has the potential to attenuate CLP-induced gut damage in mice by restraining inflammation and apoptosis via the attenuation of NF-κB signaling. It provides a basis for further study of ZJPs in sepsis.

3.
Asian J Androl ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33762476

RESUMO

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 (TEX11) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

4.
Medicine (Baltimore) ; 100(1): e24239, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429826

RESUMO

RATIONALE: Subarachnoid hemorrhages (SAHs) from ruptured intracranial aneurysms are very rare during pregnancy. Management of ruptured intracranial aneurysms with SAH in pregnancy is often challenging because of the risks to the fetus and the mother. We present the first successful awake endovascular coiling of a dissected intracranial aneurysm in a third trimester twin pregnancy. PATIENT CONCERNS: A 28 years' old pregnant woman was admitted at the obstetric department of our hospital on account of very severe headaches associated with nausea and vomiting. DIAGNOSIS: Emergency obstetric ultrasound scan done confirmed 32 weeks' twin gestation, whereas magnetic resonance imaging established hemorrhage in the suprasellar cistern and the subarachnoid space. Magnetic resonance angiography revealed a dissected aneurysm in the ophthalmic segment of the left internal carotid artery. INTERVENTIONS: Awake cerebral angiography as well as embolization of the aneurysm with coils was done via the transarterial route and the twins were delivered via caesarean section at 37 weeks' gestation. OUTCOMES: Two years' follow-up indicated no complications and children as well as their mother are healthy. LESIONS: Awake endovascular coiling was very beneficial in our case because we avoided general anesthesia and the use of osmotic diuretics which are potentially hazardous during pregnancy.


Assuntos
Aneurisma Intracraniano/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Gravidez de Gêmeos , Hemorragia Subaracnóidea/diagnóstico , Ultrassonografia Pré-Natal , Adulto , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Embolização Terapêutica , Procedimentos Endovasculares , Feminino , Cefaleia/etiologia , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Angiografia por Ressonância Magnética , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/terapia , Terceiro Trimestre da Gravidez , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/terapia
5.
Life Sci ; 262: 118543, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038381

RESUMO

AIMS: Premature ovarian failure (POF) is a phenomenon in which the ovaries fail before the age of 40 years. Prior research has used a wide range of mouse models designed to reflect different causes of POF, including genetic factors, iatrogenic factors, and immune factors. The current study employed a mouse model of POF induced by 4-vinylcyclohexene diepoxide (VCD). VCD can specifically kill primordial and primary ovarian follicles, which destroys the follicular reserve and causes POF. The current study sought to specify and extend the applications of this model by examining the effect of timing and VCD dose and by exploring the effect of the model on systems outside of the ovaries. MATERIALS AND METHODS: A VCD-induced mouse model of POF was constructed using established methods (VCD injected continuously at a concentration of 160 mg/kg for 15 days). Evidence for a graded effect of VCD was observed using a range of concentrations, and the best windows for examining VCD's effects on follicles and associated tissues were identified. KEY FINDINGS: The mouse model used here successfully simulated two common complications of POF - emotional changes and decreased bone density. The model's application was then extended to examine the links between disease and intestinal microorganisms, and evidence was found linking POF to the reproductively relevant composition of the gut microbiota. SIGNIFICANCE: These findings provide novel methodological guidance for future research, and they significantly extend the applications and scope of VCD-induced POF mouse models.

6.
Front Cell Dev Biol ; 8: 587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850784

RESUMO

Background: 4-vinylcyclohexene diepoxide (VCD) has long been considered a hazardous occupational chemical that promotes ovarian failure. However, VCD is also used as a research compound to chemically induce animal models of premature ovarian insufficiency (POI), and in related work we unexpectedly found that VCD apparently exhibits both dose- and duration-dependent opposing, hormone-like effects on the maintenance of the primordial follicle pool, follicle development, and ovulation induction. Results: We conducted experiments with cultured murine ovaries and performed transplantation experiments using postnatal day (PD) 2 and PD12 mice and found that low-dose, short-term exposure to VCD (VCDlow) actually protects the primordial/primary follicle pool and improves the functional ovarian reserve (FOR) by disrupting follicular atresia. VCDlow inhibits follicular apoptosis and regulates the Pten-PI3K-Foxo3a pathway. Short-term VCD exposure in vivo (80 mg/kg, 5 days) significantly increases the number of superovulated metaphase II oocytes, preovulatory follicles, and corpus luteum in middle-aged mice with diminished ovarian reserve (DOR). We demonstrate that low-dose but not high-dose VCD promotes aromatase levels in granulosa cells (GCs), thereby enhancing the levels of estradiol secretion. Conclusion: Our study illustrates a previously unappreciated, hormone-like action for the occupational "ovotoxin" molecule VCD and strongly suggests that VCDlow should be explored for its potential utility for treating human ovarian follicular development disorders, including subfertility in perimenopausal women.

7.
Cardiovasc Diabetol ; 19(1): 120, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746821

RESUMO

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a marker of inflammation, oxidative stress and it is associated with adverse prognosis in cardiovascular disease. The aim of the present cohort study is to investigate the prognostic value of GDF-15 in patients with coronary artery disease (CAD) during long-term follow up. METHODS: A total of 3641 consecutive patients with CAD were prospectively enrolled into the study and followed up for major adverse cardiovascular events (MACEs) and all-cause death up to 5.3-7.6 years. Plasma GDF-15 was measured and clinical data and long-term events were registered. The patients were subsequently divided into three groups by the levels of GDF-15 and the prognostic value of GDF-15 level with MACEs and all-cause death was evaluated. RESULTS: After a median follow-up at 6.4 years later, 775 patients (event rate of 21%) had developed MACEs and 275 patients died (event rate of 7.55%). Kaplan-Meier analysis indicated that the patients with GDF-15 > 1800 ng/L were significantly associated with an increased risk of MACEs and all-cause death. Cox regression analysis indicated that GDF-15 > 1800 ng/L were independently associated with the composite of MACEs (HR 1.74; 95% CI 1.44-2.02; P < 0.001) and all-cause death (HR 2.04; 95% CI 1.57-2.61; P < 0.001). For MACEs, GDF-15 significantly improved the C-statistic (area under the curve, 0.583 [95% CI 0.559-0.606] to 0.628 [0.605-0.651]; P < 0.001), net reclassification index (0.578; P = 0.031), and integrated discrimination index (0.021; P = 0.027). For all-cause death, GDF-15 significantly improved the C-statistic (0.728 [95% CI 0.694-0.761] to 0.817 [0.781-0.846]; P < 0.001), net reclassification index (0.629; P = 0.001), and integrated discrimination index (0.035; P = 0.002). CONCLUSIONS: In the setting of CAD, GDF-15 is associated with long-term MACEs and all-cause death, and provides incremental prognostic value beyond traditional risks factors.

8.
Asian J Androl ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859868

RESUMO

As a crucial transcription factor for spermatogenesis, GATA-binding protein 4 (GATA4) plays important roles in the functioning of Sertoli and Leydig cells. Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility. However, whether GATA4 is associated with human azoospermia has not been reported. Herein, we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia (NOA). We identified a missense mutation (c.191G>A, p.G64E), nine single-nucleotide polymorphisms (SNPs), and one rare variant (c.*84C>T) in the 3´ untranslated region (UTR). Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes (claudin-11 and steroidogenic acute regulatory protein, Star), and the 3´ UTR rare variant c.*84C>T did not generate microRNA-binding sites to repress GATA4 expression. To our knowledge, this is the first report to investigate the association between GATA4 and azoospermia; our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

9.
Sci Rep ; 10(1): 8993, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488141

RESUMO

PURPOSE: Polycystic ovarian morphology (PCOM) is one of the key features of polycystic ovary syndrome (PCOS). The diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is debated because of the high prevalence of PCOM in the general population. Androgen receptor (AR) is associated with the PCOS phenotype and might as well play a role during folliculogenesis. This study is aimed to investigate the expression of the AR in PCOS granulosa cells (GCs) and its relationship with the PCOM phenotype. METHODS: 106 PCOS cases and 63 controls were included from the Center for Reproductive Medicine, Shandong University. The diagnosis of PCOS was following the Rotterdam criteria (2003). Total RNA was extracted from GCs retrieved from ovarian stimulation. The expression of AR was amplified by means of quantitative real-time polymerase chain reaction. RESULTS: The AR expression was significantly decreased in PCOS cases, especially in the tPCOM subgroup (≥20 antral follicles per ovary). Correlation analyses showed that AR expression was significantly correlated with serum FSH levels in controls and non-tPCOM. In the tPCOM subgroup, the AR expression was significantly correlated with serum LH levels. Interestingly, the significance of these correlations gradually disappeared as the threshold of antral follicles increased above 24 for PCOM. CONCLUSIONS: AR was differently expressed in PCOS and especially in the tPCOM subtype. The correlation of AR expression with serum FSH and LH might be associated with the number of follicles in PCOM.

10.
Turk J Gastroenterol ; 31(4): 331-341, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32412904

RESUMO

BACKGROUND/AIMS: Accumulating evidence reveals esmolol could protect the gut mucosa through the regulation of immune response and inflammation in patients with sepsis. However, its underlying mechanism is not fully understood. MATERIALS AND METHODS: Diamine oxidase (DAO), intestinal fatty acid-binding protein (I-FABP), interleukin (IL)-6, and IL-10 in the plasma of rats were detected by ELISA assay. Western blotting was utilized to measure the expression levels of NF-kappa B-p65, Bcl-2, and cleaved caspase-3 in the intestinal tissues. The survival analysis was performed in each group. RESULTS: The plasma levels of DAO and IL-10 levels were increased, whereas that of I-FABP and IL-6 were decreased in the sepsis rats after esmolol treatment, indicating that after the esmolol treatment, the intestinal inflammation and damages were remarkably reduced as compared to those in the normal saline treated sepsis rats. NF-κB-p65 and Bcl-2 were highly expressed, but cleaved caspase-3 showed lower expression in the esmolol treated groups. However, at the same time, we observed contrasting results in the normal saline treated group. Western blotting data indicated that the esmolol treatment inhibited the inflammation and apoptosis in the intestinal tissue due to the overexpression of NF-κB-p65 in the celiac sepsis rats. The survival analysis results indicate that the esmolol infusion should be used in the early stages sepsis rats. CONCLUSION: Esmolol can suppress inflammation and apoptosis in the intestinal tissue via the overexpression of NF-kappa B-p65 in the early stage sepsis rats. kappa BEarly-stage use of esmolol might be an ideal treatment method for sepsis.

11.
Pest Manag Sci ; 76(8): 2755-2767, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32187440

RESUMO

BACKGROUND: Autophagy plays an important role in eukaryotes. We investigated its role in the pine wood nematode (PWN), Bursaphelenchus xylophilus, the causative agent of pine wilt disease (PWD), to find promising control strategies against PWD. RESULTS: We analysed the expression levels of PtRBOH1 and PtRBOH2, which regulate reactive oxygen species (ROS) metabolism, in Pinus thunbergii and the expression of three autophagy genes, BxATG5, BxATG9 and BxATG16, in PWN by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and measured the content of H2 O2 , the main product of ROS metabolism, in pine stem. There was a correlation between the expression of autophagy genes in PWN and pine ROS metabolism during early infection. We also found that oxidative stress induces autophagy in PWN according to qRT-PCR, transmission electron microscopy and Western blot analyses. Inhibition of autophagy by 3-methyladenine or silencing of the autophagy genes BxATG9 and BxATG16 in PWN showed that autophagy is essential for feeding, fecundity, egg hatching and survival of PWN under oxidative stress, confirming the importance of autophagy in the antioxidant defences of PWN. Similarly, we demonstrated that autophagy contributes to the virulence of PWN. Moreover, PWN likely ameliorates oxidative damage by enhancing the activities of the peroxidase and catalase antioxidant pathways when autophagy is inhibited. CONCLUSION: Autophagy contributes to resistance to the oxidative stress induced by pine ROS metabolism, thus promoting infection by PWN. Our findings clarify the defence mechanisms of PWN and the pathogenesis of PWD, and provide promising hints for control of PWD by blocking autophagy. © 2020 Society of Chemical Industry.


Assuntos
Autofagia , Estresse Oxidativo , Pinus , Animais , Infecções , Doenças das Plantas , Espécies Reativas de Oxigênio , Tylenchida
12.
Asian J Surg ; 43(10): 973-977, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31964584

RESUMO

BACKGROUND: Despite the risk of lymph node metastasis (LNM), the indications of endoscopic submucosal dissection (ESD) has expanded to undifferentiated type (UD-type) early gastric cancer (EGC). There is debate as to whether the endoscopic resection can be used. This study was conducted to evaluate risk factors for LNM in undifferentiated early gastric cancer, implications for the indication of the ESD so as to providing evidence for proper clinical management for UD-type EGC. METHOD: We retrospectively analyzed 203 patients with UD-type EGC who underwent gastrectomy for primary gastric adenocarcinoma between 2012 and 2017. We evaluated the relationship between the clinicopathological factors and the presence of LNM using univariable and multivariable logistic regression analyses. RESULTS: A total of 203 UD-type EGC patients were enrolled, and LNM was positive in 40 cases (19.7%). Multivariable logistic regression analysis identified three independent risk factors for LNM, the tumor size (≥2.0 cm, P < 0.001), depth of invasion (P < 0.001), and lymphatic vessel involvement (LVI, P < 0.001). LNM was observed in 5.9% patients without the three predictive factors in UD-type EGC, whereas 7.7% and 37.7% of patients with one and two risk factors had LNM, respectively. In contrast, the LNM rate was up to be 66.7% in patients with three factors. Of 41 patients satisfying the expanded indication of ESD, 3 patients (7.3%) showed LNM. LNM was not found in any of 12 patients with small intramucosal lesions (<1.0 cm) without LVI. CONCLUSIONS: LNM-related risk factors were tumor larger than 2.0 cm, submucosal invasion, and the presence of LVI in UD-type EGC. ESD alone may be sufficient treatment for the intramucosal UD-type EGC that is smaller than 1.0 cm in size. When endoscopically resected specimens show unexpectedly larger tumor size, unexpected submucosal and LVI than that determined at pre-ESD endoscopic diagnosis, an additional gastrectomy with lymphadenectomy should be considered.


Assuntos
Adenocarcinoma/cirurgia , Endoscopia Gastrointestinal/métodos , Gastrectomia/métodos , Metástase Linfática , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Humanos , Excisão de Linfonodo , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Adulto Jovem
13.
Huan Jing Ke Xue ; 40(12): 5375-5383, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854609

RESUMO

The runoff formed by rainfall carrying various land surface materials into rivers and lakes is an important factor leading to a change in water quality, and the characteristics of nitrogen and phosphorus output of rivers under different rainfall intensities are different. This study explores the impact of rainfall intensity on the water quality of the Fengyu River Watershed in the plateau agricultural region, based on the water quality monitoring data of the export section of the Fengyu River Watershed from 2011 to 2013, combined with local rainfall monitoring. The effects of four rainfall intensities (light rain, moderate rain, heavy rain, and torrential rain) on the content of different nitrogen and phosphorus components in water were analyzed. The results show that the rainfall intensity has a significant effect on the nitrogen and phosphorus emissions of the Fengyu River Watershed. The average nitrogen and phosphorus concentrations of all components are lower in light rain (<10 mm) and moderate rain (10-25 mm), and higher in heavy rain (25-50 mm) and torrential rain (50-100 mm). The percentage of NH4+-N (57.14%-76.85%) to TN is larger than that of PN (23.15%-42.86%), and the percentage of TDP (22.73%-28.00%) to TP is smaller than that of PP (72.00%-77.27%). The nitrogen concentration of different forms is:TN > NH4+-N > PN; the phosphorus concentration of different forms is:TP > PP > TDP.

14.
PLoS One ; 14(10): e0223764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613923

RESUMO

Soil pH is a critical soil quality index and controls soil microbial activities, soil nutrient availability, and plant roots growth and development. The current study aims to evaluate various pedotransfer functions for predicting soil pH using different geochemical indices (CaO, ratios of Al2O3, Fe2O3, TiO2, SiO2, MgO, and K2O to CaO) in forest soils. Various models including empirical functions (quadratic, cubic, sigmoid, logarithmic) and artificial neural network with these geochemical indices were assessed by independent testing set. Mean bias error (MBE), root mean square error (RMSE), mean absolute percentage error (MAPE), mean absolute error (MAE), coefficient of determination (R2), t-statistics (t-stat), and Akaike's Information Criterion (AIC) were applied to evaluate the model performances. Additionally, a new indicator (global performance indictor, GPI) was originally introduced in this study and was used to rank these models. According to GPI, the sigmoid functions and ANNs performed better than others. On average, they could explain above 70% of the variability in soil pH. Both model structure and dataset shape impact on model performance. The best input was CaO for ANNs, sigmoid, and logarithmic functions. The ratios of K2O to CaO and Al2O3 to CaO were the best inputs for quadratic and cubic equations, respectively.


Assuntos
Compostos de Cálcio/análise , Monitoramento Ambiental/métodos , Óxidos/análise , Solo/química , Algoritmos , China , Florestas , Concentração de Íons de Hidrogênio
15.
Int J Surg ; 71: 140-148, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568844

RESUMO

BACKGROUND: Despite increasing evidence demonstrated robot-assisted distal gastrectomy (RADG) is safe and feasible for the treatment of advanced gastric cancer (AGC), robot-assisted total gastrectomy (RATG) remains a challenging procedure due to its technical difficulties and possible postoperative complications (POCs). This study aimed to systematically evaluate POCs following RATG. METHODS: Between January 2017 and January 2019, 319 AGC patients with pathological stage T2-4aN0-3M0 who underwent RADG or RATG were enrolled. POCs were stratified using the Clavien-Dindo classification. One-to-one propensity score matching was performed to reduce confounding differences. RESULTS: After matching, 266 patients met the criteria for further analysis. Ultimately, 64 patients (24.1%) who developed POCs had 126 clinical manifestation events. Overall the POCs rate was significantly greater after RATG in comparison with RADG (29.3% vs. 18.8%; P = 0.045), and more major POCs (Clavien-Dindo grade ≥ IIIa) were observed in the RATG group (14.3% vs. 5.3%; P = 0.013). The POCs were then classified into local and systemic POCs. The rates of local POCs (35.3% vs. 19.5%; P = 0.004) and systemic POCs (24.8% vs. 15.0%; P = 0.046) were significantly higher in the RATG group than the RADG group. Subgroup analysis showed that the anastomotic leakage rate was higher after RATG (5.3% vs. 0.8%; P = 0.031), whereas the remaining POCs were similar between the two groups. Patients with higher POCs significantly had longer postoperative length of stay (R = 0.895, P = 0.003). Multivariate analysis confirmed age, extent of resection, and TNM stage were risk factors for all POCs. CONCLUSIONS: These findings demonstrated that RATG is technically feasible and safe for treatment of AGC with acceptable morbidity and mortality rates. The POCs rate of RATG was higher than RADG, especially for anastomotic leakage. More effective anastomotic techniques are needed in RATG to prevent leakage.


Assuntos
Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/patologia
16.
Int J Mol Sci ; 20(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374896

RESUMO

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is the pathogen responsible for pine wilt disease (PWD), a devastating forest disease with a pathogenic mechanism that remains unclear. Autophagy plays a crucial role in physiological and pathological processes in eukaryotes, but its regulatory mechanism and significance in PWN are unknown. Therefore, we cloned and characterized three autophagy genes, BxATG5, BxATG9, and BxATG16, in PWN. BxATG9 and BxATG16 were efficiently silenced through RNA interference, and we found that BxATG16 positively regulated the expression of BxATG5. Silencing BxATG9 and BxATG16 severely inhibited feeding and reproduction in PWN, indicating that autophagy is essential for these processes. We then examined the expression patterns of these three autophagy genes in PWN under the stresses of α-pinene and H2O2, the main defense substances of pine trees, and during the development of PWD using quantitative reverse transcription polymerase chain reaction. The expression levels of BxATG5, BxATG9, and BxATG16 all significantly increased after nematodes were stressed with α-pinene and H2O2 and inoculated into pine trees, suggesting that autophagy plays an important role in the defense and pathogenesis of PWN. In this study, the molecular characteristics and functions of the autophagy genes BxATG5, BxATG9, and BxATG16 in PWN were elucidated.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Proteínas de Helminto/genética , Pinus/parasitologia , Doenças das Plantas/parasitologia , Tylenchida/genética , Animais , Autofagia , Proteína 5 Relacionada à Autofagia/genética , Regulação da Expressão Gênica , Tylenchida/fisiologia
17.
Adv Sci (Weinh) ; 6(15): 1900295, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31406667

RESUMO

A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA-binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf  2bp2 (also commonly known as Imp2) in mouse embryos causes early embryonic developmental arrest in vitro at the 2-cell-stage. Transcriptomics and proteomics analyses of 2-cell-stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14, both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild-type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10-9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2-treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development-related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

18.
Aging (Albany NY) ; 11(15): 5829-5847, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422382

RESUMO

Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC's pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.


Assuntos
RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Regulação para Cima
19.
Sci Adv ; 5(8): eaax1101, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31453335

RESUMO

Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of Zcwpw1 in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of Zcwpw1 only somewhat slowed down meiosis prophase I progression; Zcwpw1-/- oocytes were able to complete meiosis, and Zcwpw1-/- female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Reparo do DNA por Junção de Extremidades/genética , Código das Histonas/genética , Prófase Meiótica I/genética , Oócitos/citologia , Espermatozoides/citologia , Animais , Proteínas de Ciclo Celular/genética , Quebras de DNA de Cadeia Dupla , Feminino , Histonas/genética , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores Sexuais
20.
J Surg Res ; 235: 22-33, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30691798

RESUMO

BACKGROUND: Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma. METHODS: We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients. RESULTS: Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |log2FoldChange| >2.0 and adjusted P-value < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1". CONCLUSIONS: These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adenocarcinoma/mortalidade , Biomarcadores Tumorais , Neoplasias do Colo/mortalidade , Redes Reguladoras de Genes , Humanos , Canal de Potássio KCNQ1/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Prognóstico , RNA Mensageiro/genética , Tropomiosina/genética
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