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1.
Anal Chem ; 92(7): 5082-5090, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32207605

RESUMO

Untargeted metabolomics based on liquid chromatography-mass spectrometry is affected by nonlinear batch effects, which cover up biological effects, result in nonreproducibility, and are difficult to be calibrate. In this study, we propose a novel deep learning model, called Normalization Autoencoder (NormAE), which is based on nonlinear autoencoders (AEs) and adversarial learning. An additional classifier and ranker are trained to provide adversarial regularization during the training of the AE model, latent representations are extracted by the encoder, and then the decoder reconstructs the data without batch effects. The NormAE method was tested on two real metabolomics data sets. After calibration by NormAE, the quality control samples (QCs) for both data sets gathered most closely in a PCA score plot (average distances decreased from 56.550 and 52.476 to 7.383 and 14.075, respectively) and obtained the highest average correlation coefficients (from 0.873 and 0.907 to 0.997 for both). Additionally, NormAE significantly improved biomarker discovery (median number of differential peaks increased from 322 and 466 to 1140 and 1622, respectively). NormAE was compared with four commonly used batch effect removal methods. The results demonstrated that using NormAE produces the best calibration results.

2.
J Cell Biochem ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030808

RESUMO

The tumor immune microenvironment is heterogeneous, and its impact on treatment responses is not well understood. It is still a challenge to analyze the interaction between malignant cells and the tumor microenvironment to apply suitable immunotherapy in lung adenocarcinoma. We performed the nonnegative matrix factorization method to 513 messenger RNA expression profiles of lung adenocarcinomas (LUADs) from The Cancer Genome Atlas (TCGA) to obtain an immune-related expression pattern. Subsequently, we characterized the immune-related gene signatures and clinical and survival characteristics. We used 576 patients from Gene Expression Omnibus to confirm our findings. Of the patients in the training cohort, 51% had a high immune enrichment score, high expression of immune cell signaling, cytolytic activity, and interferon (IFN)-related signatures (all P < .05). We denoted these as the Immune Class. We further subdivided the Immune Class into two subclasses based on the tumor microenvironment. These were denoted the Active Immune Class and Exhausted Immune Class. The former showed significant IFN, T-cells, M1 macrophage signatures, and better prognosis (all P < .05), while the latter presented an exhausted immune response with activated stromal enrichment, M2 macrophage signatures, and immunosuppressive factors such as WNT/transforming growth factor-ß (all P < .05). Furthermore, we predicted the response of our immunophenotypes to immunological checkpoint inhibitors (P < .05). Our findings provide a novel insight into the immune-related state of LUAD and can identify the patients who will be receptive to suitable immunotherapeutic treatments.

3.
Eur J Cancer Care (Engl) ; : e13229, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011788

RESUMO

OBJECTIVE: Cancer patients exhibit disparity in mortality risks across demographic divisions as well as insurance groups. The effects of macroeconomic environment also vary for such strata. This study analyses the gaps between mortality risks for male and female cancer patients with and without insurance and examines how such gaps transform over time with macroeconomic shifts. METHODS: Demographic, clinical and treatment records of 45,750 melanoma and 91,157 lung cancer patients diagnosed in 2007-2009 and 2011-2013 were extracted from Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier test was applied to ascertain survival probability of each insurance group, while Cox proportional hazard model was used to assess relative mortality risk for Medicaid and uninsured patients, for the whole data as well as separately for both time periods and genders. RESULTS: Both the hazard ratios and change thereof over time are greater for female patients without insurance, than for male patients. More than any insurance-gender subgroup, uninsured female patients of melanoma have much increased hazard ratios, from 1.41 [95% confidence interval (CI), 1.04-1.92] to 2.22 [95% CI, 1.67-2.94]. CONCLUSION: Despite diagnostic improvements and technology advancements, the adverse effects of macroeconomic crisis are associated with increased relative mortality risks for cancer patients without insurance, more for women than men.

4.
Metabolomics ; 16(3): 29, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32095917

RESUMO

INTRODUCTION: Colorectal cancer (CRC) remains an incurable disease. Previous metabolomic studies show that metabolic signatures in plasma distinguish CRC patients from healthy controls. Chronic enteritis (CE) represents a risk factor for CRC, with a 20 fold greater incidence than in healthy individuals. However, no studies have performed metabolomic profiling to investigate CRC biomarkers in CE. OBJECTIVE: Our aims were to identify metabolomic signatures in CRC and CE and to search for blood-derived metabolite biomarkers distinguishing CRC from CE, especially early-stage biomarkers. METHODS: In this case-control study, 612 subjects were prospectively recruited between May 2015 and May 2016, and including 539 CRC patients (stage I, 102 cases; stage II, 259 cases; stage III, 178 cases) and 73 CE patients. Untargeted metabolomics was performed to identify CRC-related metabolic signatures in CE. RESULTS: Five pathways were significantly enriched based on 153 differential metabolites between CRC and CE. 16 biomarkers were identified for diagnosis of CRC from CE and for guiding CRC staging. The AUC value for CRC diagnosis in the external validation set was 0.85. Good diagnostic performances were also achieved for early-stage CRC (stage I and stage II), with an AUC value of 0.84. The biomarker panel could also stage CRC patients, with an AUC of 0.72 distinguishing stage I from stage II CRC and AUC of 0.74 distinguishing stage II from stage III CRC. CONCLUSIONS: The identified metabolic biomarkers exhibit promising properties for CRC monitoring in CE patients and are superior to commonly used clinical biomarkers (CEA and CA19-9).

5.
Medicine (Baltimore) ; 98(44): e17679, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689786

RESUMO

To introduce the National Maternal Near Miss Surveillance System (NMNMSS) in detail and to report the composition of maternal near miss (MNM) in China.The NMNMSS was established by the National Health Commission at the end of 2010, covered over 400 health facilities from 30 provinces in China. The NMNMSS was designed to collect individual information for every pregnant woman admitted to obstetric department in the sampled health facilities. Cross tabulations and correlations were used to describe the distribution of population and sampled facilities in the NMNMSS, and to calculate the MNM mortality ratio for different complications and organ dysfunctions.The individual survey forms of 9,051,638 pregnant women were collected in the NMNMSS between 2012 and 2017. Compared with urban areas, there are very few well-quality medical resources in rural areas. Most women with pregnancy complications in rural areas can only be treated in Level 2 and lower hospitals. MNM in women with indirect obstetric complications received treatment more frequently in Level 3 hospital. The most common maternal complications in severe maternal outcomes (including maternal near miss and maternal death) are obstetrics hemorrhage (58.7%), hypertension disorder (28.0%), and severe anemia (20.6%). The overall MNM mortality ratio is 38:1. The MNM mortality ratios are lowest in amniotic fluid embolism, HIV/AIDS, heart disease, thrombophlebitis, and sepsis. For different organ dysfunctions, the ranks of the MNM mortality ratio from low to high are renal dysfunction, respiratory dysfunction, cardiovascular dysfunction, hepatic dysfunction, neurologic dysfunction, uterine dysfunction, coagulation dysfunction.The NMNMSS is a well-established hospital-based surveillance system for maternal complications in China. It can identify the maternal complications that need to improve health care immediately in China through a powerful longitudinal real-world evidence.


Assuntos
Near Miss/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Vigilância em Saúde Pública/métodos , China/epidemiologia , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Complicações do Trabalho de Parto/epidemiologia , Gravidez , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos
6.
BMJ Open ; 9(8): e031474, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31444193

RESUMO

OBJECTIVE: This study examines the incidence and spatial clustering of phenylketonuria (PKU) in China between 2013 and 2017. METHODS: Data from the Chinese Newborn Screening Information System were analysed to assess PKU incidence with 95% CIs by province, region and disease severity. Spatial clustering of PKU cases was analysed using global and local spatial autocorrelation analysis in the geographic information system. RESULTS: The database contained 4925 neonates with confirmed PKU during the study period, corresponding to an incidence of 6.28 (95% CI: 6.11 to 6.46) per 100 000 neonates screened. Incidence was highest in the provinces of Gansu, Ningxia and Qinghai, where it ranged from 19.00 to 28.63 per 100 000 neonates screened. Overall incidence was higher in the northern part of the country, where classical disease predominated, than in the southern part, where mild disease predominated. PKU cases clustered spatially (global Moran's I=0.3603, Z=5.3097, p<0.001), and local spatial autocorrelation identified four northern provinces as high-high clusters (Gansu, Qinghai, Ningxia and Shanxi). CONCLUSIONS: China shows an intermediate PKU incidence among countries, and incidence differs substantially among Chinese provinces and between northern and southern regions. Our results suggest the need to focus efforts on screening, diagnosing and treating PKU in high-incidence provinces.

7.
Biosci Rep ; 39(8)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31285389

RESUMO

BACKGROUND: Intervertebral disc degeneration is a common degenerative disease. The present study aimed to explore the role and mechanism of tension-induced endoplasmic reticulum stress in intervertebral disc degeneration. METHODS: Intervertebral disc degeneration models of SD rat were analyzed for apoptosis, the expression of Poly(ADP-ribose) polymerase (PARP), Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP using immunohistochemistry, qPCR and Western blot analysis. Annulus fibrosus cells of intervertebral disc were isolated, subjected to cyclic deformation stress and analyzed for ROS and apoptosis, lysosome activity and expression of genes. The cells were knockdown with siRNA or treated with endoplasmic reticulum stress inhibitor 4-PBA and assayed for ROS, apoptosis, lysosome activity and gene expression. RESULTS: Compared with the controls, intervertebral disc degeneration was observed through X-rays examinations and HS staining. Apoptosis and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly increased in the intervertebral disc tissue of the models. In mechanic mimic experiments, the primary annulus fibrosus cells were subjected to 18% cyclic deformation, ROS and apoptosis as well as the activity of lysosome were increased. Similarly, the expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP was also increased significantly after deformation treatment. On other hand, when the cells were treated with 9 mM 4-PBA and/or CHOP-siRNA4, the apoptosis rate, ROS level, lysosome activity and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly reduced. CONCLUSIONS: Autophagy reaction mediated by endoplasmic reticulum stress plays important rale in tension-induced intervertebral disc degeneration. Intervertebral disc degeneration likely results from interactions between autophagy, apoptosis and reticulum stress, and is ROS-dependent.

8.
PLoS One ; 14(6): e0217835, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170204

RESUMO

OBJECTIVE: To describe the epidemiology of holoprosencephaly (HPE) in China with special reference to prevalence and associated anomalies. METHODS: Data were abstracted from the Chinese Birth Defects Monitoring Network for the period 2007-2014. Birth prevalence of HPE were assessed by birth year, fetal/infant sex, maternal age, and maternal residential area. Poisson regressions were used to calculate the crude and adjusted prevalence ratios (PR) and their 95% confidence intervals, and linear chi-square test was used to explore time trend for the prevalence of HPE. RESULTS: A total of 1222 HPE cases were identified in 13,284,142 births, yielding an overall prevalence of 0.92 per 10,000 births. The annual prevalence of HPE presented an upward trend (P<0.001), from 0.54 per 10,000 births in 2007 to 1.21 per 10,000 births in 2014. Higher prevalence was found in older maternal-age groups (30-34 years, adjusted PR: 1.19, 95% CI: 1.02-1.40; ≥35 years, adjusted PR: 1.53, 95% CI: 1.26-1.86) in comparison with the maternal-age group of 25 to 29 years. Higher prevalence was also found in infants born to mothers resided in urban areas (adjusted PR: 1.23, 95% CI: 1.08-1.39) and female infants (adjusted PR: 1.30, 95% CI: 1.15-1.47). CONCLUSIONS: HPE is an important perinatal health issue because of its poor prognosis. This is the first study depicting a picture of epidemiological characteristics of HPE in China, which can provide useful references for future studies.


Assuntos
Holoprosencefalia/epidemiologia , Vigilância da População , Adulto , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Adulto Jovem
9.
Sci Rep ; 9(1): 6452, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015608

RESUMO

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.

10.
Anal Chim Acta ; 1061: 60-69, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-30926040

RESUMO

Metabolomics provides new insights into disease pathogenesis and biomarker discovery. Samples from large-scale untargeted metabolomics studies are typically analyzed using a liquid chromatography-mass spectrometry platform in several batches. Batch effects that are caused by non-biological systematic biases are unavoidable in large-scale metabolomics studies, even with properly designed experiments. The statistical analysis of large-scale metabolomics data without managing batch effects will yield misleading results. In this study, we propose a novel algorithm, called WaveICA, which is based on the wavelet transform method with independent component analysis, as the threshold processing method to capture and remove batch effects for large-scale metabolomics data. The WaveICA method uses the time trend of samples over the injection order, decomposes the original data into multi-scale data with different features, extracts and removes the batch effect information in multi-scale data, and obtains clean data. The WaveICA method was tested on real metabolomics data. After applying the WaveICA method, scattered quality control samples (QCS) and subject samples in a PCA score plot of the original data were closely clustered, respectively. The average Pearson correlation coefficients for all peaks of the QCS increased from 0.872 to 0.972. Additionally, WaveICA significantly improved the classification accuracy for metabolomics data. The method was compared with three representative methods, and outperformed all of them. To conclude, WaveICA can efficiently remove batch effects while revealing more biological information. This method can be used in large-scale untargeted metabolomics studies to preprocess raw metabolomics data.


Assuntos
Algoritmos , Metabolômica , Análise de Ondaletas , Controle de Qualidade
11.
J Cell Biochem ; 120(8): 13330-13341, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30916827

RESUMO

Renal clear cell carcinoma (RCC) patients who do not achieve optimal control of progression with immune checkpoint blockade (ICB) should be further studied. Unsupervised consensus clustering was used to group 525 RCC patients based on two typical ICB pathways, CTLA-4 and pogrammed death 1 (PD-1)/programmed death-ligand 1 (PD-L1), as well as two new discovered regulators, CMTM6 and CMTM4. Three immune molecular subtypes (IMMSs) with different clinical and immunological characteristics were identified (type I, II, and III), among which there were more stage I and low-grade tumors in type I RCC than in type II and III. The proportion of males was highest in type II RCC. Overall survival of type II and III was similar (5.2 and 6 years) and statistically shorter than that of type I (7.6 years) before and after adjusting for age and gender. When conducting stratified analysis, our IMMSs were able to identify high-risk patients among middle-aged patients, males, and stage IV patients. Among the differentially expressed genes, approximately 84% were highly expressed in type II and III RCC. Genes related to ICB (CTLA-4, CD274, and PDCD1LG2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type II and III RCC. These results documented that patients with type II and III cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. High expression of CMTM4 in type I RCC (69%) and a statistically significant interaction of CD274 and CMTM6 indicated that CMTM4/6 might be new therapy targets for type I, who are resistant to ICB.

12.
PLoS One ; 14(1): e0209962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650106

RESUMO

OBJECTIVE: Until now, little was known about the epidemiological characteristics of twins in China due to a lack of reliable national data. In this study, we aimed to analyze temporal trends and perinatal mortality of twins from China. METHODS: Data on twins between 2007 and 2014 were obtained from the China National Population-Based Birth Defects Surveillance System. Twin and singleton deliveries after at least 28 weeks of gestation were recruited and followed until postnatal day 42. Twinning rates were defined as the number of twin individuals per 1000 births(stillbirths and live births). The Weinberg's differential method was utilized to estimate the number of monozygotic and dizygotic twins. RESULTS: During 2007-2014, the twinning rate increased by 32.3% from 16.4 to 21.7 per 1000 total births with an average of 18.8‰. Among twins, both the perinatal mortality rate (26.1 per 1000 total births) and neonatal death rate (15.7 per 1000 live births) presented a downward tendency but remained at a high level. Large urban-rural and geographic disparities were identified in twinning rates, in perinatal and neonatal mortality, and in their temporal trends. CONCLUSIONS: The upward trend of twinning rates in China paired with the relatively high rates of perinatal and neonatal mortality among twins highlights the need for improved perinatal care in the light of socio-demographic differences.


Assuntos
Coeficiente de Natalidade , Mortalidade Infantil , Natimorto/epidemiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Retrospectivos , População Rural , Fatores Socioeconômicos , População Urbana
13.
Sci Rep ; 9(1): 273, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670707

RESUMO

Postterm births are associated with an increased risk of adverse perinatal outcomes, but few studies have investigated the epidemiological characteristics of postterm births. We aimed to estimate the prevalence of postterm births and examine the potential association between maternal sociodemographic and obstetric characteristics and postterm births. Data were collected from China's National Maternal Near Miss Surveillance System, 2012-2016. A logistic regression was used to assess the association between sociodemographic and obstetric characteristics and postterm births. A Poisson regression was used to determine the crude and adjusted trends of postterm births over time across regions. Among the 6,240,830 singleton births with gestational periods of 37 weeks or longer, 1.16% were postterm. The prevalence of postterm births was significantly higher in the western region and among mothers who delivered at a level ≤2 hospital, had a lower education, or were younger. A reduced risk of postterm births was observed among primiparous women, mothers who previously had a caesarean section, mothers with pregnancy complications, and mothers with ten or more antenatal visits. The risk of postterm births decreased as the number of antenatal visits increased. The overall postterm birth rates significantly decreased from 1.49% in 2012 to 0.70% in 2016. The postterm birth rates were markedly reduced in the east, central, and west regions, and the rate of the decrease was greater in the east than in the west. Furthermore, substantial decreases were observed across regions in 2014 and 2016. In conclusion, multiple sociodemographic and obstetric factors are associated with the prevalence of postterm births. A significant decreasing trend in postterm birth rates was observed in China.

14.
Lancet ; 393(10168): 241-252, 2019 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-30554785

RESUMO

BACKGROUND: As one of only a handful of countries that have achieved both Millennium Development Goals (MDGs) 4 and 5, China has substantially lowered maternal mortality in the past two decades. Little is known, however, about the levels and trends of maternal mortality at the county level in China. METHODS: Using a national registration system of maternal mortality at the county level, we estimated the maternal mortality ratios for 2852 counties in China between 1996 and 2015. We used a state-of-the-art Bayesian small-area estimation hierarchical model with latent Gaussian layers to account for space and time correlations among neighbouring counties. Estimates at the county level were then scaled to be consistent with country-level estimates of maternal mortality for China, which were separately estimated from multiple data sources. We also assessed maternal mortality ratios among ethnic minorities in China and computed Gini coefficients of inequality of maternal mortality ratios at the country and provincial levels. FINDINGS: China as a country has experienced fast decline in maternal mortality ratios, from 108·7 per 100 000 livebirths in 1996 to 21·8 per 100 000 livebirths in 2015, with an annualised rate of decline of 8·5% per year, which is much faster than the target pace in MDG 5. However, we found substantial heterogeneity in levels and trends at the county level. In 1996, the range of maternal mortality ratios by county was 16·8 per 100 000 livebirths in Shantou, Guangdong, to 3510·3 per 100 000 livebirths in Zanda County, Tibet. Almost all counties showed remarkable decline in maternal mortality ratios in the two decades regardless of those in 1996. The annualised rate of decline across counties from 1996 to 2015 ranges from 4·4% to 12·9%, and 2838 (99·5%) of the 2852 counties had achieved the MDG 5 pace of decline. Decline accelerated between 2005 and 2015 compared with between 1996 and 2005. In 2015, the lowest county-level maternal mortality ratio was 3·4 per 100 000 livebirths in Nanhu District, Zhejiang Province. The highest was still in Zanda County, Tibet, but the fall to 830·5 per 100 000 livebirths was only 76·3%. 26 ethnic groups had population majorities in at least one county in China, and all had achieved declines in maternal mortality ratios in line with the pace of MDG 5. Intercounty Gini coefficients for maternal mortality ratio have declined at the national level in China, indicating improved equality, whereas trends in inequality at the provincial level varied. INTERPRETATION: In the past two decades, maternal mortality ratios have reduced rapidly and universally across China at the county level. Fast improvement in maternal mortality ratios is possible even in less economically developed places with resource constraints. This finding has important implications for improving maternal mortality ratios in developing countries in the Sustainable Development Goal era. FUNDING: National Health and Family Planning Commission of the People's Republic of China, China Medical Board, WHO, University of Washington Center for Demography and Economics of Aging, Bill & Melinda Gates Foundation.


Assuntos
Mortalidade Materna , Teorema de Bayes , China/epidemiologia , Países em Desenvolvimento , Feminino , Carga Global da Doença , Humanos , Nascimento Vivo/epidemiologia , Sistema de Registros , População Rural , População Urbana
15.
Anal Chem ; 91(3): 2401-2408, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30580524

RESUMO

The metabolic profiling of biofluids using untargeted metabolomics provides a promising choice to discover metabolite biomarkers for clinical cancer diagnosis. However, metabolite biomarkers discovered in biofluids may not necessarily reflect the pathological status of tumor tissue, which makes these biomarkers difficult to reproduce. In this study, we developed a new analysis strategy by integrating the univariate and multivariate correlation analysis approach to discover tumor tissue derived (TTD) metabolites in plasma samples. Specifically, untargeted metabolomics was first used to profile a set of paired tissue and plasma samples from 34 colorectal cancer (CRC) patients. Next, univariate correlation analysis was used to select correlative metabolite pairs between tissue and plasma, and a random forest regression model was utilized to define 243 TTD metabolites in plasma samples. The TTD metabolites in CRC plasma were demonstrated to accurately reflect the pathological status of tumor tissue and have great potential for metabolite biomarker discovery. Accordingly, we conducted a clinical study using a set of 146 plasma samples from CRC patients and gender-matched polyp controls to discover metabolite biomarkers from TTD metabolites. As a result, eight metabolites were selected as potential biomarkers for CRC diagnosis with high sensitivity and specificity. For CRC patients after surgery, the survival risk score defined by metabolite biomarkers also performed well in predicting overall survival time ( p = 0.022) and progression-free survival time ( p = 0.002). In conclusion, we developed a new analysis strategy which effectively discovers tumor tissue related metabolite biomarkers in plasma for cancer diagnosis and prognosis.

16.
Clin Chim Acta ; 487: 357-362, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296444

RESUMO

BACKGROUND: Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. METHODS: In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis. RESULTS: Metabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5'-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC. CONCLUSIONS: Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Metabolômica , Biomarcadores Tumorais/sangue , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Análise Multivariada
17.
Bull World Health Organ ; 96(8): 548-557, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30104795

RESUMO

Objective: To examine the trends and safety of vaginal birth after caesarean section around the period of the one-child policy relaxation in China. Methods: We used data from China's National Maternal Near Miss Surveillance System between 2012 and 2016. To examine trends in vaginal birth after caesarean section, we used Poisson regression with a robust variance estimator. We also assessed the association between vaginal birth after caesarean section and maternal and perinatal outcomes. Findings: We analysed 871 636 deliveries by women with a previous caesarean section. Both in 2012 and 2016, the rate of vaginal birth after caesarean section was 9.8%. After adjusting for institutional, sociodemographic and obstetric characteristics, the rate increased by 14% between 2012 and 2016 (adjusted relative risk, aRR: 1.14; 95% confidence interval, CI: 1.07-1.21). Compared to women with a repeat caesarean section, women with a vaginal birth after caesarean section experienced lower incidence of uterine rupture (aRR: 0.26, 95% CI: 0.16-0.42), blood transfusion (aRR: 0.68, 95% CI: 0.53-0.87) and admission to the intensive care unit (aRR: 0.36, 95% CI: 0.25-0.52), but higher incidence of intrapartum stillbirths, (aRR: 7.20, 95% CI: 6.09-8.51), newborns with a 5-minute Apgar score less than 7 (aRR: 1.75, 95% CI: 1.54-1.99) and neonatal death before discharge (aRR: 1.90, 95% CI: 1.61-2.24). Conclusion: Promotion of vaginal birth after caesarean section could increase the rate even further in China. To ensure the safety of mothers and their newborns, national policies and guidelines on vaginal birth after caesarean section are needed.


Assuntos
Cesárea , Nascimento Vaginal Após Cesárea/estatística & dados numéricos , Peso ao Nascer , Cesárea/efeitos adversos , Criança , China , Feminino , Humanos , Recém-Nascido , Parto , Gravidez , Ruptura Uterina/prevenção & controle , Nascimento Vaginal Após Cesárea/tendências
18.
J Cell Biochem ; 119(10): 8564-8573, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30126000

RESUMO

Serous ovarian cancer (SOC) is the most common form of the histological subtype of epithelial ovarian cancer, with the worst clinical outcome. Despite improvements in surgery and chemotherapy, most patients with SOC experience recurrence within 12-18 months of first-line treatment. Current studies are unable to robustly predict the recurrence of SOC, and more accurate predictive models are urgently required. We have, therefore, developed a novel pathway-structured model to predict the recurrence of SOC. We trained the model on a set of 333 patients and validated it in 3 diversified validation datasets of 403 patients. Genes significantly associated with recurrence within each pathway were identified using a Cox proportional hazards model based on LASSO estimation in the training dataset. Next, a pathway-structured scoring matrix was obtained after computation of the prognostic score for each pathway by fitting to the Cox proportional hazards model. With the pathway-structure scoring matrix as an input, the pathway-based recurrent signatures were identified using the Cox proportional hazards model based on LASSO estimation and the significant pathway-based signatures were externally validated in 3 independent datasets. Meanwhile, our pathway-structured model was compared with a commonly used gene-based model. Our results revealed that our 12 pathway-based signatures successfully predicted the recurrence of SOC with high accuracy in the training dataset and in the 3 validation datasets. Moreover, our pathway-structured model was superior to the gene-based model in 4 datasets. The pathways selected in our study will provide new insights into the pathogenesis and clinical treatments of SOC.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Redes e Vias Metabólicas/genética , Modelos Biológicos , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/metabolismo , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Confiabilidade dos Dados , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC
19.
Gynecol Oncol ; 150(3): 460-465, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30001833

RESUMO

OBJECTIVE: To assess the association between patterns of distant metastases and overall survival in metastatic ovarian cancer and identify prognostic factors for site-specific distant metastases. METHODS: Data was obtained from the SEER database between 2010 and 2014. Univariate and multivariate Cox proportional hazard models were used to identify variables associated with overall survival. Survival times between different groups were compared using Kaplan-Meier analysis and log-rank tests. RESULTS: We analyzed 1481 patients. The most common distant metastatic site was liver, followed by distant lymph nodes, lung, bone, and brain. The site of distant metastases was an independent prognostic factor for overall survival. Using liver metastases as reference, overall survival was lower for lung metastases (p = 0.0297) and higher for distant lymph node metastases (p = 0.0006). Using distant lymph nodes as reference, distant metastases to the liver (p = 0.0006), lung (p < 0.0001), brain (p = 0.0455), and bone (p = 0.0138) were all associated with worse overall survival. The number of metastatic sites did not affect overall survival. We also found that surgery and chemotherapy affected overall survival for patients with distant lymph node metastases only; age, histological subtype, surgery, and chemotherapy affected overall survival for patients with liver metastases only, while histological subtype and chemotherapy affected overall survival for patients with lung metastases only. CONCLUSIONS: The site of distant metastases affected overall survival in metastatic ovarian cancer. Patients with specific distant metastatic sites should receive special treatment and management. The identified prognostic factors can help clinician evaluate the prognosis for ovarian cancer patients with distant metastases.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Modelos de Riscos Proporcionais , Programa de SEER , Taxa de Sobrevida , Estruturas Linfoides Terciárias , Estados Unidos/epidemiologia
20.
J Pediatr Endocrinol Metab ; 31(6): 601-608, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29715190

RESUMO

BACKGROUND: Congenital hypothyroidism (CH) is one of the most frequent, preventable causes of mental retardation. Little has been reported on the epidemiological characteristics of CH in China. We aimed to estimate the incidence of CH in China and investigate its geographical variation. METHODS: We analyzed data from the nationwide newborn screening program for CH between 2013 and 2015. Poisson regression was used to generate the odds ratios (ORs) and 95% confidence intervals (CIs) between the rates of CH and selected demographic characteristics and assess the potential association between CH incidence and geographical locations. RESULTS: A total of 18,666 patients with CH were identified from 45.2 million newborns, yielding an overall incidence rate of 4.13 per 10,000 live births. Compared with those in the remote area, regardless of infant sex, a higher incidence risk for CH was present in newborns in coastal areas and inland areas (females: OR=2.00, 95% CI: 1.86-2.16 and OR=1.74, 95% CI: 1.61-1.87, respectively; males: OR=1.70, 95% CI: 1.59-1.83 and OR=1.52, 95% CI: 1.42-1.63, respectively). Additionally, the highest risk of CH for thyroid-stimulating hormone (TSH) screening values <40 mU/L was observed among neonates in the coastal areas, while TSH screening values of 70-100 mU/L were observed among those in the inland areas. CONCLUSIONS: The overall incidence of CH is high in China. The significant geographical variations of CH incidence are presented in this study.


Assuntos
Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/epidemiologia , China/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Triagem Neonatal , Avaliação de Programas e Projetos de Saúde
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