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1.
JMIR Public Health Surveill ; 10: e53860, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829691

RESUMO

BACKGROUND: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. OBJECTIVE: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. METHODS: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. RESULTS: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90). CONCLUSIONS: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances.


Assuntos
Mortalidade da Criança , Anormalidades Congênitas , Humanos , China/epidemiologia , Masculino , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/epidemiologia , Feminino , Lactente , Pré-Escolar , Recém-Nascido , Mortalidade da Criança/tendências , Vigilância da População/métodos , Análise de Dados
2.
Front Neurol ; 15: 1347682, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895693

RESUMO

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

3.
Nat Commun ; 14(1): 7476, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978295

RESUMO

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.


Assuntos
Caenorhabditis elegans , Fatores de Diferenciação de Crescimento , Adulto , Camundongos , Humanos , Animais , Caenorhabditis elegans/metabolismo , Fatores de Diferenciação de Crescimento/genética , Fatores de Diferenciação de Crescimento/metabolismo , Envelhecimento/genética , Encéfalo/metabolismo , Neurônios/metabolismo , Proteínas Morfogenéticas Ósseas
4.
Cell Death Discov ; 8(1): 147, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365618

RESUMO

Receptor interacting serine/threonine protein kinase 1 (RIPK1) activation and necroptosis have been genetically and mechanistically linked with human multiple sclerosis and neurodegenerative diseases for which demyelination is a common key pathology. Demyelination can be healed through remyelination which is mediated by new oligodendrocytes derived from the adult oligodendrocyte progenitor cells (OPCs). Unfortunately, the efficiency of remyelination declines with progressive aging partially due to the depletion of OPCs following chronic or repeated demyelination. However, to our knowledge, so far there is no drug which enhances proliferation of OPCs, and it is unknown whether inhibiting RIPK1 activity directly affect OPCs, the central player of remyelination. Using TNFα induced RIPK1-dependent necroptosis in Jurkat FADD-/- cells as a cell death assay, we screened from 2112 FDA-approved drugs and the drug candidates of new RIPK1 inhibitors selected by ourselves, and identified ZJU-37, a small molecule modified by introducing an amide bond to Nec-1s, is a new RIPK1 kinase inhibitor with higher potency than Nec-1s which has the best reported potency. We unveil in addition to protecting myelin from demyelination and axons from degeneration, ZJU-37 exhibits a new role on promoting proliferation of OPCs and enhancing remyelination by inhibiting RIPK1 kinase activity with higher potency than Nec-1s. Mechanistically, ZJU-37 promotes proliferation of OPCs by enhancing the transcription of platelet derived growth factor receptor alpha via NF-κB pathway. This work identifies ZJU-37 as a new drug candidate which enhances remyelination by promoting proliferation of OPCs, paving the way for a potential drug to enhance myelin repair.

5.
Nat Commun ; 13(1): 1225, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264567

RESUMO

The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing. When we supplement ß-nicotinamide mononucleotide (ß-NMN), an NAD+ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD+-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD+ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.


Assuntos
Células Precursoras de Oligodendrócitos , Remielinização , Envelhecimento , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Camundongos , Bainha de Mielina , NAD , Células Precursoras de Oligodendrócitos/fisiologia , Oligodendroglia/fisiologia , Remielinização/fisiologia , Sirtuína 2/genética
6.
Abdom Radiol (NY) ; 46(4): 1659-1669, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32997155

RESUMO

PURPOSE: To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). METHODS: After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. RESULTS: Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P < 0.000, P = 0.001, 0.001, and 0.005, respectively) than the NC group. ADC was negatively correlated with glucose, and MR2*, MCR and glucose showed a weak positive correlation. CONCLUSION: DWI and BOLD may indirectly and qualitatively reflect the kidney microstructure status and hypoxia level of diabetic patients at different blood glucose levels to a certain extent, and possibly guide the clinical treatment of diabetic patients with different blood glucose levels.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Jejum , Humanos , Rim , Imageamento por Ressonância Magnética
7.
J Pharm Biomed Anal ; 193: 113731, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33197833

RESUMO

Cloperastine hydrochloride, a piperidine derivative, is a drug substance with a central antitussive effect and widely used in cough treatment; and its impurities have not been reported. Herein we isolated and identified five impurities (named as impurity A, B, C, D and E) in cloperastine hydrochloride bulk drug and developed a quantitative HPLC method. First, impurity A, B, C were enriched by ODS column chromatography and isolated by semi-preparative HPLC, at the same time, impurity D was purified by ODS column chromatography. Then, impurity E was enriched by strong acid degradation and purified by semi-preparative HPLC. At last, their structures were characterized by a variety of spectral data (MS, 1H NMR, 13C NMR, HSQC, HMBC and 1H-1H COSY). Impurity A was confirmed as 1-[2-(diphenylmethoxy)ethyl]piperidine, which having one less chloro-substituent compared with cloperastine. Impurity B was confirmed as 1-[2-[(2-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 2-chloro-substituent. Impurity C was confirmed as 1-[2-[(3-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 3-chloro-substituent. Impurity D was confirmed as (4-chlorophenyl)(phenyl)methanone, which was the raw material for the synthesis of cloperastine. Impurity E was confirmed as (4-chlorophenyl)(phenyl)methanol, which was an intermediate in the synthesis of cloperastine, and it was also a hydrolysate of cloperastine. Finally, the developed method was validated in terms of specificity, linearity, sensitivity, precision and accuracy.


Assuntos
Contaminação de Medicamentos , Piperidinas , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética
8.
Asian Pac J Cancer Prev ; 14(12): 7127-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24460263

RESUMO

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.


Assuntos
Neoplasias Colorretais/etiologia , Mutação/genética , Receptores de Laminina/genética , Proteínas Ribossômicas/genética , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Fatores de Risco
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