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1.
Can J Gastroenterol Hepatol ; 2021: 5685610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746041

RESUMO

Background: Accurate dyssynergic defecation (DD) diagnosis depends on anorectal physiological tests that are not widely available. Aim: The purpose of this study is to evaluate the diagnostic yield of digital rectal examination (DRE) compared with anorectal physiological tests in diagnosing DD in patients with constipation. Methods: A total of 218 chronic constipation patients who fulfilled the Rome IV diagnostic criteria for functional constipation (FC) and underwent a standardized DRE and high-resolution anorectal manometry (HRAM) test were enrolled in this study. The diagnostic accuracy of DRE compared with HRAM was evaluated, and the agreement between DRE and HRAM was calculated. Furthermore, a comprehensive literature search on PubMed, Web of Science, Cochrane Library, and Embase database was conducted to further elucidate the pooled diagnostic accuracy of DRE in DD patients. Results: A total of 101 patients (46.33%) had a DD pattern using HRAM, while 117 patients (53.67%) were diagnosed without DD. The sensitivity of DRE in diagnosing dyssynergia was 71.3%, and the specificity was 76.1%. There was a moderate agreement between DRE and HRAM for diagnosing DD (κ-coefficient = 0.474, P < 0.001). Meanwhile, six studies (including our study) comprising 964 constipated patients were included in our meta-analysis. The outcomes demonstrated that the AUC was 0.85 (95% CI 0.82-0.88) with 77% summary sensitivity (95% CI 65-86) and 80% summary specificity (95% CI 71-86) to diagnose DD. Conclusions: DRE could be a valuable tool for screening DD. Our study revealed acceptable sensitivity and specificity of DRE in detecting dyssynergia compared with the physiological tests. Meanwhile, our study highlights that DRE remains an important tool in clinical practice.

2.
Nat Commun ; 12(1): 6310, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728626

RESUMO

SHP2 mediates the activities of multiple receptor tyrosine kinase signaling and its function in endothelial processes has been explored extensively. However, genetic studies on the role of SHP2 in tumor angiogenesis have not been conducted. Here, we show that SHP2 is activated in tumor endothelia. Shp2 deletion and pharmacological inhibition reduce tumor growth and microvascular density in multiple mouse tumor models. Shp2 deletion also leads to tumor vascular normalization, indicated by increased pericyte coverage and vessel perfusion. SHP2 inefficiency impairs endothelial cell proliferation, migration, and tubulogenesis through downregulating the expression of proangiogenic SRY-Box transcription factor 7 (SOX7), whose re-expression restores endothelial function in SHP2-knockdown cells and tumor growth, angiogenesis, and vascular abnormalization in Shp2-deleted mice. SHP2 stabilizes apoptosis signal-regulating kinase 1 (ASK1), which regulates SOX7 expression mediated by c-Jun. Our studies suggest SHP2 in tumor associated endothelial cells is a promising anti-angiogenic target for cancer therapy.

3.
World J Diabetes ; 12(9): 1576-1586, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34630909

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disorder worldwide, and there is no established treatment for this disease. We conducted a network meta-analysis (NMA) to compare existing treatments, which include four classes of antidiabetic drugs, and examined the optimum treatments for NAFLD. AIM: To compare the effectiveness of different treatments for NAFLD. METHODS: An NMA was conducted using Stata 14.0 (Corporation LLC, College Station, United States) and R (X64 3.6.3 version) in this study. Eligible randomized controlled trials (RCTs) were searched in the PubMed, Cochrane Library, Embase, Medline and Web of Science databases from database inception to April 2021. Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference, respectively. An inconsistency model and "node-splitting" technique were used to test for inconsistency. Funnel plots were used to evaluate publication bias. RESULTS: Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis. Data were pooled using a random-effects model. Our NMA results revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were the most effective treatment, yielding improvements in hepatic fat content (HFC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum γ-glutamyl transferase (GGT) and body weight [surface under the cumulative ranking curve (SUCRA) = 99.6%, 92.6%, 82.8%, 92.3% and 99.6%, respectively], while thiazolidinediones (TZDs) were the best intervention for reducing the NAFLD activity score (NAS; SUCRA = 98.9%). In addition, moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups (SUCRA = 25.1%, 66.2%, 63.5%, 58.2% and 71.9% for HFC, ALT, AST, GGT and body weight, respectively). However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively). CONCLUSION: GLP-1RAs may be the optimum choice for most patients with NAFLD. However, TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.

4.
BMC Pediatr ; 21(1): 442, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625039

RESUMO

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases with clinical and genetic heterogeneity, and CDG-IIg is one of the rare reported types of CDG. The aim of this study is to report the clinical manifestations and gene-phenotype characteristics of a rare case of CDG caused by a COG1 gene mutation and review literatures of CDG disease. CASE PRESENTATION: The patient was male, and the main clinical symptoms were developmental retardation, convulsion, strabismus, and hypoglycemia, which is rarely reported in CDG-IIg. We treated the patient with glucose infusion and he was recovered from hypoglycemia. Genetic analysis showed that the patient carried the heterozygous intron mutation c.1070 + 3A > G (splicing) in the coding region of the COG1 gene that was inherited from the mother, and the heterozygous mutation c.2492G > A (p. Arg831Gln) in exon 10 of the COG1 gene that was inherited from the father. The genes interacting with COG1 were mainly involved in the transport and composition of the Golgi. The clinical data and laboratory results from a patient diagnosed with CDG-IIg were analyzed, and the causative gene mutation was identified by high-throughput sequencing. The genes and signal pathways related to COG1 were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. CONCLUSIONS: The c.2492G > A (p. Arg831Gln) mutation in exon 10 of the COG1 gene may be a potential pathogenetic variant for CDG-IIg. Because of the various manifestations of CDG in clinical practice, multidisciplinary collaboration is important for the diagnosis and treatment of this disease.


Assuntos
Defeitos Congênitos da Glicosilação , Hipoglicemia , Proteínas Adaptadoras de Transporte Vesicular/genética , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Complexo de Golgi , Heterozigoto , Humanos , Hipoglicemia/genética , Masculino , Mutação
5.
Oxid Med Cell Longev ; 2021: 6657658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646426

RESUMO

Previous studies on serum fetuin-B (fetuin-like protein IRL685) have investigated its association with T2DM; however, the reason for the variation in serum fetuin-B and its regulatory factors in metabolic disease remain unclear. Here, we evaluated serum fetuin-B levels in women with newly diagnosed MetS and performed multiple interventions to investigate the role of fetuin-B in the pathogenesis of MetS. Serum fetuin-B levels were assessed using ELISA. Bioinformatics analysis was performed to analyze fetuin-B-related genes and signaling pathways. Additionally, oxidative stress parameters were measured in the in vitro study. For subgroup analyses, we performed EHC, OGTT, and treatment with a GLP-1RA to investigate the regulatory factors of serum fetuin-B. We found that in comparison with healthy subjects, serum fetuin-B levels were markedly increased in women with MetS. Further, serum fetuin-B showed a positive correlation with WHR, FAT%, TG, FBG, HbA1c, FIns, HOMA-IR, VAI, and LAP. Bioinformatics analysis revealed that most fetuin-B-related core genes were involved in cholesterol metabolism and fat decomposition. Consistent with this finding, multivariate regression analysis showed that triglyceride content and WHR were independently associated with serum fetuin-B. We also observed that serum fetuin-B levels were markedly elevated in healthy subjects after glucose loading and in women with MetS during EHC. In vitro, overexpression of fetuin-B promoted oxidative stress in HepG2 cell. After 6 months of treatment with a GLP-1RA, serum fetuin-B levels in women with MetS decreased following an improvement in metabolism and insulin sensitivity. Therefore, serum fetuin-B is associated with MetS, which may serve as a biomarker of oxidative stress. This trial is registered with ChiCTR-OCC-11001422.

6.
ACS Omega ; 6(38): 24515-24525, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34604633

RESUMO

The distribution of hydroxyl (OH) radicals in the laminar diffusion flame of n-heptane was studied by planar laser-induced fluorescence (PLIF). The influences of nitrogen (N2) and carbon dioxide (CO2) dilution on the formation and distribution of OH radicals were analyzed. The corresponding dilution ratios (volume fractions) of both N2 and CO2 vary from 0 to 5%. The results show that for the n-heptane flame, the OH radical is mainly concentrated in the two wings of the flame, presenting a radially approximate symmetrical distribution. Both N2 and CO2 dilutions decrease the intensity of the maximum OH radical fluorescence and the total OH radical fluorescence. Moreover, the flame temperature decreases more significantly with the CO2 dilution ratio due to the combination of the dilution effect and thermal effect.

7.
Ecotoxicol Environ Saf ; 225: 112731, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488147

RESUMO

Homeostasis disturbance of trace elements has been linked to adverse reproductive consequences, including premature ovarian insufficiency (POI) in women, but limited evidence has been reported so far. This case-control study evaluated the associations between 5 common urinary trace elements [copper (Cu), manganese (Mn), Iron (Fe), Selenium (Se), and zinc (Zn)] and the odds for POI. Urinary concentrations of these 5 metals and serum levels of POI-related reproductive hormones of 169 cases and 209 healthy controls were measured. The urinary levels of Cu and Se in women with POI were significantly higher than those in the controls. The positive associations were observed between Cu levels and the odds of POI [for the medium tertile: odds ratio (OR) = 3.79, 95% CI: 1.98-7.27, p < 0.001; for the highest tertile: OR = 3.85, 95% CI: 2.00-7.41, p < 0.001]. The highest tertile of urinary Se levels was associated with increasing POI risk (for the highest tertile: OR = 2.54, 95% CI: 1.38-4.70, compared with the lowest tertile, p for trend = 0.001). In POI patients, urinary concentrations of Zn and Fe were negatively associated with serum levels of follicle-stimulating hormone (FSH). Our findings suggested that higher exposure levels of Cu and Se might lead to an increased risk of POI.


Assuntos
Insuficiência Ovariana Primária , Oligoelementos , Estudos de Casos e Controles , China , Feminino , Hormônio Foliculoestimulante , Humanos
8.
PLoS Biol ; 19(8): e3001360, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34347783

RESUMO

Pathogenic fungi precisely respond to dynamic microenvironments during infection, but the underlying mechanisms are not well understood. The insect pathogenic fungus Metarhizium robertsii is a representative fungus in which to study broad themes of fungal pathogenicity as it resembles some major plant and mammalian pathogenic fungi in its pathogenesis. Here we report on a novel cascade that regulates response of M. robertsii to 2 distinct microenvironments during its pathogenesis. On the insect cuticle, the transcription factor COH2 activates expression of cuticle penetration genes. In the hemocoel, the protein COH1 is expressed due to the reduction in epigenetic repression conferred by the histone deacetylase HDAC1 and the histone 3 acetyltransferase HAT1. COH1 interacts with COH2 to reduce COH2 stability, and this down-regulates cuticle penetration genes and up-regulates genes for hemocoel colonization. Our work significantly advances the insights into fungal pathogenicity in insects.


Assuntos
Proteínas Fúngicas/metabolismo , Interações Hospedeiro-Patógeno , Metarhizium/fisiologia , Mariposas/microbiologia , Animais , Microambiente Celular , Proteínas Fúngicas/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/metabolismo , Metarhizium/patogenicidade , Estabilidade Proteica , Fatores de Transcrição/metabolismo
9.
Front Endocrinol (Lausanne) ; 12: 713475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367075

RESUMO

Background: The preoperative distinguishment of lymph nodes with reactive hyperplasia or tumor metastasis plays a pivotal role in guiding the surgical extension for papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT), especially in terms of the central lymph node (CLN) dissection. We aim to identify the preparative risk factors for CLN metastasis in PTC patients concurrent with HT. Materials and Methods: We retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and thyroid function of consecutive PTC patients with HT in our medical center between Jan 2019 and Apr 2021. The Chi-square and Fisher's exact tests were used for comparison of qualitative variables among patients with or without CLN metastasis. Univariate and multivariate logistic regression analyses were used to determine the risk factors for CLN metastasis. The nomogram was constructed and further evaluated by two cohorts produced by 1,000 resampling bootstrap analysis. Results: A total of 98 in 214 (45.8%) PTC patients were identified with CLN metastasis. In multivariate analysis, four variables including high serum thyroglobulin antibody (TgAb) level (>1,150 IU/ml), lower tumor location, irregular margin of CLN, and micro-calcification in the CLN were determined to be significantly associated with the CLN metastasis in PTC patients with HT. An individualized nomogram was consequently established with a favorable C-index of 0.815 and verified via two internal validation cohorts. Conclusions: Our results indicated that preoperatively sonographic characteristics of the tumor and lymph node condition combined with serum TgAb level can significantly predict the CLN in PTC patients with HT and the novel nomogram may further help surgeons to manage the CLN in this subpopulation.

10.
BMC Neurol ; 21(1): 294, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34311705

RESUMO

OBJECTIVE: To compare the effectiveness of various drug interventions in improving the clinical outcome of postoperative patients after aneurysmal subarachnoid hemorrhage (aSAH) and assist in determining the drugs of definite curative effect in improving clinical prognosis. METHODS: Eligible Randomized Controlled Trials (RCTs) were searched in databases of PubMed, EMBASE, and Cochrane Library (inception to Sep 2020). Glasgow Outcome Scale (GOS) score, Extended Glasgow Outcome Scale (GOSE) score or modified Rankin Scale (mRS) score was used as the main outcome measurements to evaluate the efficacy of various drugs in improving the clinical outcomes of postoperative patients with aSAH. The network meta-analysis (NMA) was conducted based on a random-effects model, dichotomous variables were determined by using odds ratio (OR) with 95% confidence interval (CI), and a surface under the cumulative ranking curve (SUCRA) was generated to estimate the ranking probability of comparative effectiveness among different drug therapies. RESULTS: From the 493 of initial citation screening, forty-four RCTs (n = 10,626 participants) were eventually included in our analysis. Our NMA results showed that cilostazol (OR = 3.35,95%CI = 1.50,7.51) was the best intervention to improve the clinical outcome of patients (SUCRA = 87.29%, 95%CrI 0.07-0.46). Compared with the placebo group, only two drug interventions [nimodipine (OR = 1.61, 95%CI 1.01,2.57) and cilostazol (OR = 3.35, 95%CI 1.50, 7.51)] achieved significant statistical significance in improving the clinical outcome of patients. CONCLUSIONS: Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol may be the best drug to improve the outcome of patients after aSAH operation. Our study provides implications for future studies that, the combination of two or more drugs with relative safety and potential benefits (e.g., nimodipine and cilostazol) may improve the clinical outcome of patients more effectively.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Cilostazol/uso terapêutico , Aneurisma Intracraniano/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nimodipina/uso terapêutico , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/cirurgia , Metanálise em Rede , Período Pós-Operatório , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento
11.
BMC Endocr Disord ; 21(1): 121, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130678

RESUMO

BACKGROUND: Previous studies have indicated that women with a history of menstrual disorders have an increased risk of metabolic and cardiovascular diseases. This has been attributed to the high proportion of polycystic ovary syndrome (PCOS) among this group. The favorable effects of hormone replacement therapy (HRT) on serum lipid profiles and glucose homeostasis in postmenopausal women is widely accepted. Whether HRT can also show positive effects on metabolic homeostasis in menopausal women with prior menstrual disorders (a putative PCOS phenotype) has not been reported yet. The aim of the study was to compare the effects of HRT on glucose and lipid metabolism in peri- and postmenopausal women with prior menstrual disorders and controls who did not have prior menstrual disorders. METHODS: A retrospective multicenter study was conducted including 595 peri- and postmenopausal women who received HRT at four hospitals in the Zhejiang Province from May 31, 2010 to March 8, 2021. Participants were divided into the Normal menstruation group and the Menstrual disorders group according to their prior usual menstrual cycle pattern. Glucose and lipid metabolism indicators were assessed at baseline and after HRT. The results were compared between and within the groups, and data from peri- and postmenopausal women were analyzed separately. RESULTS: HRT significantly decreased fasting insulin and homeostasis model assessment of insulin resistance in perimenopausal users, and fasting plasma glucose levels in postmenopausal users with prior menstrual disorders, compared with baseline. Furthermore, HRT decreased low-density lipoprotein cholesterol, total cholesterol, fasting insulin, fasting plasma glucose and homeostasis model assessment of insulin resistance in both peri- and postmenopausal controls, compared with baseline. Nevertheless, no significant differences were observed in any of the glucose or lipid metabolism indicators at baseline and follow-up, as well as changes from baseline levels between menopausal women with and without prior menstrual disorders. CONCLUSIONS: HRT shows more obvious within-group improvements in glucose and lipid metabolism in controls, but there is no significant between-group difference. Further prospective studies are required for confirmation.

12.
Blood ; 138(16): 1441-1455, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34075404

RESUMO

Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation, but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesized that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, and RUNX1) bind key hematopoietic genes in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other's, regulatory elements. However, their mutual regulation during normal hematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. In this study, we integrated bulk and single-cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists, with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and leukemic cells. The heptad factors GATA2, TAL1, and ERG formed an integrated subcircuit that regulates stem cell-to-erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits can be harnessed to promote specific cell-type transitions and overcome dysregulated hematopoiesis.

13.
Cancer Manag Res ; 13: 3963-3971, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017199

RESUMO

Background: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers. Methods: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p<0.05 was considered significant. Results: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT. Conclusion: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.

14.
Maturitas ; 148: 33-39, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34024349

RESUMO

OBJECTIVE: . To compare the metabolic profile of women with spontaneous premature ovarian insufficiency (POI) with that of age-matched healthy controls. STUDY DESIGN: . A cross-sectional case-control study was conducted using 1:1 matching by age. Women below the age of 40 with spontaneous POI who did not receive any medication (n = 303) and age-matched healthy women (n = 303) were included in this study. MAIN OUTCOME MEASURES: . Metabolic profiles, including serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, uric acid, urea and creatinine, were compared between women with POI and controls. For women with POI, factors associated with the metabolic profile were analyzed. RESULTS: . Women with POI were more likely to exhibit increased serum levels of TG (ß, 0.155; 95% CI, 0.086, 0.223) and glucose (0.067; 0.052, 0.083), decreased levels of HDL-C (-0.087; -0.123, -0.051), LDL-C (-0.047; -0.091, -0.003) and uric acid (-0.053; -0.090, -0.015), and impaired kidney function (urea [0.070; 0.033, 0.107]; creatinine [0.277; 0.256, 0.299]; eGFR [-0.234; -0.252, -0.216]) compared with controls after adjusting for age and BMI. BMI, parity, gravidity, FSH and E2 levels were independent factors associated with the metabolic profile of women with POI. CONCLUSION: . Women with POI exhibited abnormalities in lipid metabolism, glucose metabolism, and a decrease in kidney function. In women with POI, early detection and lifelong management of metabolic abnormalities are needed.


Assuntos
Biomarcadores/metabolismo , Menopausa Precoce/metabolismo , Metaboloma , Insuficiência Ovariana Primária/metabolismo , Adulto , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Insuficiência Ovariana Primária/patologia , Triglicerídeos/sangue , Adulto Jovem
15.
Front Cell Dev Biol ; 9: 588278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842454

RESUMO

Absent in melanoma 2 (AIM2), a DNA sensor that plays an important role in natural immunity system, has been reported to participate in colorectal cancer (CRC) development. However, the functional role of AIM2 in BRAF-mutant CRC remains unclear. In this study, we first investigated AIM2 expression level in BRAF-mutant CRC tumor tissues. Overexpression of AIM2 in CRC cells was performed to investigate the effect of AIM2 on CRC cell viability, and cell death detection and caspase activity assay were performed to explore the mechanism that AIM2 impacts the growth of BRAF-mutant CRC cells. Moreover, we confirmed the antitumor effect of AIM2 in BRAF-mutant CRC cell-derived tumor xenograft (CDX) models as well as patient-derived organoids (PDOs). Herein, we reported that AIM2 expression was lower in BRAF-mutant than that in BRAF wild-type CRC tumor tissues. Restoring the expression of AIM2 in BRAF-mutant CRC cells greatly inhibits the tumor cell growth by inducing necrotic cell death. Mechanism studies revealed that AIM2-induced cell death is in a caspase-1-dependent manner. Additionally, overexpression of AIM2 significantly inhibits tumor growth and metastasis in BRAF-mutant CRC in vivo, which was further confirmed in BRAF-mutant CRC PDOs. Taken together, our data suggested that AIM2 inhibits BRAF-mutant colon cancer growth in a caspase-1-dependent manner, which may provide evidence to understand the pathogenesis of CRC with BRAF-mutant, as well as new strategies for manipulation of CRC.

16.
J Obstet Gynaecol Res ; 47(4): 1481-1486, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33438304

RESUMO

AIM: The aim of this study is to investigate the role of vitamin E in the etiology of premature ovarian insufficiency (POI). METHODS: This study included a total of 96 matched cases and controls, including the case group composed of 40 women with POI, and the control group composed of 56 women with normal menstrual cycles. Serum levels of vitamin E (also known as α-tocopherol), total cholesterol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were determined. The relationship of α-tocopherol with FSH, LH and AMH levels in women were evaluated using regression models. RESULTS: We found a negative association of α-tocopherol levels with FSH and LH levels, and a positive correlation between a-tocopherol and AMH levels in the whole study population. In this study, α-tocopherol levels were significantly lower in women with POI than those in women with normal menstrual cycles. CONCLUSION: Vitamin E levels showed significantly statistical difference between the POI and control group (P < 0.001). Therefore, vitamin E is correlated to POI.


Assuntos
Menopausa Precoce , Insuficiência Ovariana Primária , Hormônio Antimülleriano , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante , Humanos , Vitamina E
17.
Menopause ; 28(5): 529-537, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33470756

RESUMO

OBJECTIVE: To comprehensively investigate and evaluate the prevalence, severity, and associated factors of menopausal symptoms in women with premature ovarian insufficiency (POI). In this study, the specific symptomatology experienced by women with POI and women with natural menopause was also compared. METHODS: In this cross-sectional study, 293 Chinese women with POI from an outpatient clinic were recruited between June 2014 and January 2019. The prevalence and severity of menopausal symptoms were assessed with modified Kupperman Menopausal Index. Participants completed a structured questionnaire, including medical history, menstrual characteristics, and sociodemographic data. Serum levels of reproductive hormones were measured. RESULTS: Among 293 women with POI (33.76 ±â€Š5.47 y), the most prevalent symptoms were mood swings (73.4%), insomnia (58.7%), sexual problems (58.7%), and fatigue (57.3%). Moderate-to-severe mood swings were most frequently reported (23.9%), followed by formication (17.4%) and hot flashes/sweating (17.1%). Compared with women with natural menopause, women with POI exhibited significantly higher risks for fatigue (odds ratio  = 1.42; 95% confidence interval, 1.04-1.94), melancholia (3.12; 1.94-5.01), mood swings (3.57; 2.33-5.45), insomnia (1.41; 1.02-1.96), and significantly lower risks for moderate-to-severe sexual problems (0.40; 0.23-0.69), any and moderate-to-severe muscle/joint pain (0.41; 0.27-0.62 and 0.45; 0.25-0.78, respectively). Living in urban areas and higher gravidity were independently associated with menopausal symptoms in women with POI. CONCLUSIONS: Women with POI experienced a high prevalence of menopausal symptoms, particularly related to psychological and sexual domains. Furthermore, women with POI tended to have more distressing menopausal symptoms compared with women with natural menopause.


Assuntos
Fogachos , Menopausa Precoce , Estudos Transversais , Feminino , Fogachos/epidemiologia , Humanos , Menopausa , Prevalência , Inquéritos e Questionários
18.
Environ Res ; 195: 110776, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33516685

RESUMO

AIMS: To investigate the impact of occupation types on age at natural menopause. METHODS: This is a nation-wide cross-sectional study based on 17,948 female workers aged over 40, who come from different industries or organizations. A face-to-face standardized questionnaire was conducted in all participants with the help of occupational hygienists. Occupational titles were coded according to the International Standard Classification of Occupations (2008) (ISCO08). Cox regression model was used to assess the association between each independent occupation and menopausal timing. Models were adjusted for marriage, education, average annual family income, parity, cigarette smoking, alcohol consumption. RESULTS: Higher risks of earlier age at natural menopause was found among legislators and senior officials (ISCO Minor group:111, HR = 2.328, P < 0.001), among other health associated professionals (ISCO Minor group: 325, HR = 1.477, P = 0.003), the workers involved in mining and mineral processing (ISCO Minor group: 811, HR = 1.515, P = 0.048) and metal processing and finishing (ISCO Minor group: 812, HR = 1.722, P < 0.001). Reduced risks of earlier age at natural menopause, including: finance professionals (ISCO Minor group: 241, HR = 0.751, P = 0.021), manufacturing and construction supervisors (ISCO Minor group: 312, HR = 0.477, P = 0.002), administrative and specialized secretaries (ISCO Minor group: 334, HR = 0.788, P = 0.045), cleaners and helpers (ISCO Minor group: 911, HR = 0.633, P = 0.01). CONCLUSIONS: This is the first study to address the influence of occupation types on reproductive aging, showing some specific occupations could be associated with age at natural menopause. Further investigations are necessary to clarify whether it is chance finding or a true association.


Assuntos
Menopausa , Ocupações , Idoso , China , Estudos Transversais , Feminino , Humanos , Indústrias , Gravidez
20.
Reprod Biomed Online ; 41(6): 1045-1053, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32962927

RESUMO

RESEARCH QUESTION: Does uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? DESIGN: Prospective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5-7 days after embryo transfer (ET5-7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. RESULTS: Uterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5-7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5-7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5-7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5-7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5-7 in women with ongoing pregnancies. CONCLUSIONS: This study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF.

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