Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33838095

RESUMO

BACKGROUND: Tetrahydrobiopterin deficiency (BH4D), a less common form of hyperphenylalaninemia (HPA), can lead to severe developmental retardation if untreated. Little has been reported on the prevalence of BH4D among live births worldwide. This study examined its prevalence across China and between geographical areas within the country. METHODS: We analyzed data from the Chinese national screening program for HPA in newborns between 2013 and 2019. BH4D prevalence was examined by province, region and the entire country. Provincial-level prevalence was estimated from the number of confirmed BH4D cases and screened newborns, after adjusting for HPA-positive recall rate. Regional- and national-level prevalences were estimated by summing provincial-level prevalences after weighting them by the number of live births. A Poisson distribution was assumed in order to calculate 95% confidence intervals (CIs) for prevalence. RESULTS: Among 107,078,115 newborns screened for HPA in China, 380 with BH4D were identified, corresponding to a total prevalence of 3.8 per 1,000,000 live births. Prevalence was higher in eastern regions (5.9 per 1,000,000) and northern regions (4.1 per 1,000,000) of China than in southern regions (1.6 per 1,000,000) or northwestern regions (1.7 per 1,000,000). Across the entire country, 3.9% cases of HPA were diagnosed as BH4D, and this proportion reached as high as 15.1% in the southern part of the country. CONCLUSIONS: These first insights into BH4D prevalence across China suggest slightly higher prevalence than in other countries, and it varies substantially by region. More attention should be paid to early diagnosis and timely treatment of BH4D.

2.
Twin Res Hum Genet ; 24(1): 22-28, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33775270

RESUMO

The purpose of our study was to elucidate the functions of miR-30c-5p on adenomyosis for exploring novel treatment strategies. We first detected the expression of miR-30c-5p in clinical adenomyotic tissues and isolated endometrial cells from adenomyotic tissues. Next, gain and loss-of-function assays were performed to detect the effect of miR-30c-5p on adenomyotic endometrial cells. Further, luciferase assay and real-time polymerase chain reaction as well as western blot were conducted to investigate the potential target of miR-30c-5p; and transwell assay, wound-healing assay and CCK-8 assay were used to evaluate the effects of miR-30c-5p and its target on regulating biological functions of adenomyotic endometrial cells. Our results found that miR-30c-5p was down-regulated in both adenomyosis tissues and adenomyotic epithelial cells, which correlated with dysmenorrhea, longer duration of symptoms and more menstrual bleeding. Moreover, the overexpression of miR-30c-5p inhibited the proliferation, migration and invasion of adenomyotic epithelial cells, where miR-30c-5p knockdown had an opposite effect. Furthermore, we confirmed mitogen-activated protein kinase 1 (MAPK1) was one of the direct targets of miR-30c-5p, indicating its important role in miR-30c-5p-mediated suppression of proliferation, invasion and migration in adenomyotic epithelial cells. This study showed that the interaction of miR-30c-5p with MAPK1 can regulate the proliferation, invasion and migration in adenomyotic epithelial cells.

3.
Arch Gynecol Obstet ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635405

RESUMO

PURPOSE: Patients with lung metastases (LM) from epithelial ovarian cancer (EOC) (EOCLM) usually have a poor prognosis. However, there is no consensus on the optimal management of these patients. In this study, we aimed to take a look at the incidence of LM and factors associated with its occurrence as well as the prognosis in newly diagnosed EOC with LM on a population level. METHODS: EOC patients diagnosed between the years 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. Multivariable logistic regression and multivariable Cox regression were used to investigate the factors that could predict the occurrence of and prognosis after diagnosis of EOC with LM. RESULTS: Of the 33,418 qualified EOC patients, 2240 (6.7%) were noted to have LMs at the time of EOC diagnosis. Higher T stage, N1 stage, advanced tumor grade, and elevated cancer antigen-125 levels were found to be associated with a higher risk of having LM at the time of EOC diagnosis. The median survival time after diagnosis with EOCLM was found to be 13.0 months (interquartile range: 3.0-34.0 months). Being unmarried and having mucinous histology were both associated with increased all-cause death risk from EOCLM. However, the primary tumor originated from the midline of ovaries, surgical management, and whether patient received chemotherapy or not predicted improved overall survival. The median survival time of patients was significantly longer for EOCLM cases managed surgically (31.0 months) versus those who did not have surgery (4.0 months), as well as EOCLM cases received chemotherapy (23.0 months) versus those who did not have chemotherapy (2.0 months). CONCLUSION: This retrospective cohort study showed that de novo LM was infrequent in EOC patients overall and when present predicted poor prognosis. The findings can be potentially useful in formulating for follow-up strategies, screening tools, and personalized interventions.

4.
Epigenomics ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290106

RESUMO

Aims: Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Materials & methods: Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. Results: A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. Conclusion: This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.

5.
J Med Screen ; : 969141320973690, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33241759

RESUMO

BACKGROUND: The incidence of inborn errors of metabolism varies widely across countries. Very few studies have analyzed the incidence of these disorders in Mainland China. We aimed to estimate the overall and disease-specific incidences of inborn errors of metabolism in Chinese newborns and investigate the geographical distribution of these disorders. METHODS: A national cross-sectional survey was conducted to investigate newborn inborn errors of metabolism screening by tandem mass spectroscopy in Mainland China between 2016 and 2017. A total of 246 newborn screening centers were surveyed using a standardized questionnaire. We examined the cumulative and disease-specific incidences of inborn errors of metabolism in Mainland China as a whole and in different geographical locations. RESULTS: Over 7 million newborns were screened and 2747 were diagnosed with inborn errors of metabolism, yielding an overall incidence of 38.69 per 100,000 births (95% confidence interval: 37.27-40.17). The most common disorders were amino acid disorders (17.14 per 100,000 births, 95% confidence interval: 16.21-18.13), followed by organic acid disorders (12.39 per 100,000 births, 95% confidence interval: 11.60-13.24) and fatty acid oxidation disorders (9.16 per 100,000 births, 95% confidence interval: 8.48-9.89). The overall and disease-specific incidence rates differed significantly across geographical locations (P < 0.001). CONCLUSIONS: The overall incidence of inborn errors of metabolism in Chinese newborns is relatively high. It is urgent to establish the recommended uniform screening panel for inborn errors of metabolism to guide the national and regional tandem mass spectroscopy newborn screening programs.

6.
BMC Pediatr ; 20(1): 360, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32731854

RESUMO

BACKGROUND: Newborn hearing screening (NHS) can reduce the economic and social burden of hearing impairment. To track the progress of the goal set by the National Program of Action for Child Development (NPACD) and to estimate the detection rates of hearing impairment, the present study examined NHS coverage in 2008-2010 and 2016 and the detection of hearing impairment across China in 2016. METHODS: Licensed medical institutions across China were surveyed in 2012 and 2018 by the National Center for Birth Defects Monitoring of China to collect data for the 2008-2010 period and for 2016 on live births, initial screening rates (total and referral), secondary screening rates (total and referral), and rates of hearing impairment diagnosis among infants who were referred in the secondary screening. To calculate universal newborn hearing screening (UNHS) coverage, the number of newborns who received NHS within 4 weeks after birth was divided by the number of live births. The detection rate of hearing impairment was calculated by combining referral rates on primary and secondary screening with the rate of diagnosis. RESULTS: National UNHS coverage increased from 29.9% in 2008 to 86.5% in 2016, with different regions showing different increases. During this period, the number of provinces with UNHS coverage over 90.0% increased from 2 to 17, with UNHS coverage in 2016 being substantially higher in eastern provinces (93.1%) than in western provinces (79.4%). In 2016, the detection rate of hearing impairment across the country was 0.23% (95% CI 0.15-0.25%), and it varied from 0.17% in western provinces to 0.22% in central provinces and 0.28% in eastern provinces. The lowest rate was 0.02% in Heilongjiang Province and the highest rate was 0.63% in Hainan Province. CONCLUSIONS: National UNHS coverage increased substantially from 2008 to 2016, although provinces and regions still showed differences. The detection rate of infant hearing impairment in China is comparable to that in other countries. A national individual-level information system is urgently needed in China to facilitate the integration of screening, diagnosis and treatment of infant hearing impairment, which may also lead to a more accurate estimate of the detection rate.

7.
J Cancer ; 11(16): 4861-4869, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626533

RESUMO

Background: Primary Epithelial Ovarian Cancer (EOC), a malignant gynecologic disease, is considered one of the leading causes of mortality in women. The development of Liver Metastases (LM) in women with primary ovarian cancer commonly results in a poorer prognosis. This retrospective population-based study aims to measure the prevalence, prognostic factors, and associated risk factors for epithelial ovarian cancer patients with liver metastases (EOCLM). Materials and Methods: The current study cohort of patients based on the Surveillance, Epidemiology, and End Results (SEER) database identified with primary ovarian cancer between the years 2010 and 2016. A chi-square test was employed to compare Metastatic differences among demographic and clinical factors. Univariable and multivariable logistic regression analysis models were used to predict related prognostic factors for LM development. 7-year Kaplan-Meier curves were applied to compare the survival patterns of patients with and without LM. The Multivariable Cox regression model was used to estimate potential risk factors associated with LM related deaths. Results: 33895 eligible primary EOC patients were identified. Among them 2635 (7.77%) patients were initially diagnosed with de novo LM, and 31260 (92.23%) without metastases disease to any site. Non-serous histology type; Malignant Brenner Carcinoma, NOS (OR 1.94; CI: 1.39-2.71; P<0.001), T3/T1 stage (OR 5.65; CI: 3.87-8.24; P<0.001), N1/N0 stage (OR 1.67; CI: 1.43-4.95; P<0.001), grade; G3/G1 (OR 2.16; CI: 1.29-3.59, P<0.001), and cancer antigen-125; Elevated/Normal (OR 1.79; CI: 1.19-2.69, P<0.001) were significantly associated with LM occurrence. The median survival of EOC patients with LM was 12.0 (95% CI: 11.0-14.0; P<0.001) months. Multivariable cox regression showed being unmarried (HR 1.16; CI: 1.04-1.30; P=0.001), non-serous histology types, Mucinous (HR 2.38; CI: 1.82-3.12; P<0.001), Clear cell (HR 1.83; CI: 1.32-2.55; P<0.001), Malignant Brenner Carcinoma, NOS (HR 1.44; CI:1.23-1.66; P<0.001), Carcinosarcoma NOS, (HR 1.44; CI: 1.11-1.88; P<0.001) and radiotherapy (HR 1.52; CI: 1.12-2.06; P<0.001), were positively related to death. Chemotherapy (HR 0.30; CI: 1.12-2.06; P<0.001) and surgery (HR 0.34; CI: 0.29-0.39; P<0.001) were related with reduced rate of death. Conclusion: The retrospective cohort study showed that women with primary EOC had some high-risk factors associated with LM. LM can intensely decrease the survival of EOC patients. The findings of our research provided estimates for LM occurrence prediction and potential prognostic factors of EOC with de novo LM development. These findings can be useful for follow-up strategies, guidelines for screening, and treatment of EOCLM.

8.
Public Health ; 185: 130-138, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622220

RESUMO

OBJECTIVES: Health insurance availability and affordability are vital elements in diagnosis and treatment of patients with cancer and thus constitute clinical significance as well. Although past studies have explored the disparity in mortality figures for patients with different insurance statuses, this population-based study is pioneering in analyzing the changes in cancer mortality risks over time amid macroeconomic shifts. STUDY DESIGN: The study uses Surveillance Epidemiology and End Results (SEER) data of 424,889 non-elderly patients with breast, cervical, ovarian, and uterine cancer diagnosed during 2007-2010 and 2011-2015. METHODS: In addition to discussing incidence figures and insurance patterns, the study uses Kaplan-Meier and Cox's proportional hazard models to examine the changes in survival probability and mortality risks for insurance-stratified patients with female-specific cancer across the two time periods. RESULTS: Patients without insurance have an increased risk of mortality over time relative to insured patients. Moreover, uninsured patients face this heightened risk more than Medicaid patients. DISCUSSION: Despite public policy measures as well as advancements in diagnostic facilities and treatment technology, the increased relative mortality of patients without insurance limits the long-term affordability of cancer treatment for economically vulnerable patients in comparison with insured patients.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/mortalidade , Adolescente , Adulto , Neoplasias da Mama/mortalidade , Feminino , Humanos , Incidência , Cobertura do Seguro/economia , Seguro Saúde/economia , Medicaid/economia , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias Ovarianas/mortalidade , Fatores de Risco , Programa de SEER , Estados Unidos , Neoplasias do Colo do Útero/mortalidade , Neoplasias Uterinas/mortalidade , Adulto Jovem
9.
Anal Chem ; 92(7): 5082-5090, 2020 04 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.

10.
Cancer Manag Res ; 12: 793-799, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099475

RESUMO

Objective: Ascites, an accumulation of peritoneal fluid, is associated with poor prognosis of certain cancers. The potential mechanism that ascites worsens prognosis has not been well understood. Lipids have been reported to correlate with the prognosis of patients with epithelial ovarian cancer (EOC). Therefore, we aimed here to investigate whether lipids mediate the effect of ascites on the recurrence of EOC. Methods: We collected the demographic and pathological data of 437 previously untreated patients with EOC to investigate the influence of ascites on recurrence. To identify the mechanism that mediates the potential influence of ascites on recurrence, we used ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to determine the plasma lipid profiles of 53 patients with EOC. We used mediation analysis to evaluate if lipids mediated the effects of ascites on the recurrence of EOC. Results: Patients with ascites had a poorer prognosis, which was associated with higher levels of carbohydrate antigen-CA125 (CA125) and FIGO stage. We identified six different lipid metabolites that were associated with ascites and recurrence. Mediation analysis revealed that the lipids LysoPC(P-15:0), PC(P-34:4), and PC(38:6) may mediate the effects of ascites on recurrence. Conclusion: Our findings suggest that LysoPC(P-15:0), PC(P-34:4), and PC(38:6) mediate the effect of ascites on the prognosis of patients with EOC. We believe therefore that it is reasonable to consider metabolic interventions targeting the metabolism of LysoPC(P-15:0), PC(P-34:4), and PC(38:6) as a palliative treatment for patients with EOC with ascites. Further studies of more patients will be required to validate our findings.

11.
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).

12.
J Cell Biochem ; 121(11): 4569-4579, 2020 Nov.
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.

13.
Eur J Cancer Care (Engl) ; 29(4): e13229, 2020 Jul.
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.

14.
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
15.
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.


Assuntos
Fenilcetonúrias/epidemiologia , China/epidemiologia , Análise por Conglomerados , Feminino , Sistemas de Informação Geográfica , Humanos , Incidência , Recém-Nascido , Masculino , Triagem Neonatal , Análise Espacial
16.
Biosci Rep ; 39(8)2019 08 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.


Assuntos
Autofagia/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Animais , Apoptose/fisiologia , Proteína Beclina-1/metabolismo , Caspase 12/metabolismo , Caspase 3/metabolismo , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Lisossomos/metabolismo , Lisossomos/fisiologia , Masculino , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo
17.
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
18.
Sci Rep ; 9(1): 6452, 2019 04 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.


Assuntos
Algoritmos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
J Cell Biochem ; 120(8): 13330-13341, 2019 08.
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.


Assuntos
Carcinoma de Células Renais/metabolismo , Imunofenotipagem/métodos , Idoso , Antígeno B7-H1/metabolismo , Antígenos CD8/metabolismo , Antígeno CTLA-4/metabolismo , Carcinoma de Células Renais/imunologia , Feminino , Granzimas/metabolismo , Humanos , Proteínas com Domínio MARVEL/metabolismo , Masculino , Pessoa de Meia-Idade , Perforina/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...