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OBJECTIVES: Menopause is a significant life transition for women, impacting their physical and psychological health. The age at natural menopause (ANM) and its associated factors have differed by race and region. This study aimed to investigate ANM and associated factors of early and late menopause among Chinese women in Zhejiang province. METHODS: A cross-sectional study was conducted using a multi-stage stratified cluster sampling method to recruit 8,006 women aged 40-69 years who had resided in Zhejiang province for over 6 months between July 2019 and December 2021. Self-reported ANM and sociodemographics, lifestyle behaviors, reproductive history, and health-related factors were collected using questionnaires in face-to-face surveys. ANM were categorized into three groups: early menopause (<45 years), normal menopause (45-54 years), and late menopause (≥55 years). Kaplan-Meier survival analysis was utilized to calculate the median ANM. Multivariable multinomial logistic regression was employed to explore the associated factors of early menopause and late menopause. RESULTS: A total of 6,047 women aged 40-69 years were included for survival analysis, with 3,176 of them for the regression analysis. The overall median ANM was 51 years (Inter-quartile range [IQR]: 51-52). Women who were smokers (odds ratio [OR]:4.54, 95% confidence interval [CI]:1.6-12.84), had irregular menstrual cycles (OR:1.78, 95% CI:1.12-2.83) and hypertension (OR:1.55, 95% CI:1.09-2.21) had a higher odds ratio of early menopause, while central obesity (OR:1.33, 95% CI:1.03-1.73) and hyperlipidemia (OR:1.51, 95% CI:1.04-2.18) were factors associated with late menopause. CONCLUSIONS: This study revealed the associations between ANM and various factors among Chinese women. These factors included socio-demographic factors such as age; life behavior factors like current or prior smoking status; reproductive history factors such as irregular menstrual cycles, miscarriages, and breastfeeding; and health-related factors like central adiposity, hypertension, and hyperlipidemia. These findings provided a basis for understanding factors associated with ANM.
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Menopausia , Humanos , Femenino , Persona de Mediana Edad , Menopausia/fisiología , Estudios Transversales , Adulto , China/epidemiología , Anciano , Factores de Edad , Factores de Riesgo , Menopausia Prematura/fisiología , Encuestas y Cuestionarios , Estilo de Vida , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos de Fenilurea , Quinolinas , Neoplasias Gástricas , alfa-Fetoproteínas , Humanos , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Anciano , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Adulto , PronósticoRESUMEN
BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.
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Neoplasias del Colon , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Estudios de Cohortes , InmunoterapiaRESUMEN
Acupuncture has demonstrated positive efficacy in the treatment of brain disorders. However, significant challenges lie in integrating acupuncture with modern technologies, promoting its clinical application in treating brain disorders, elucidating the mechanisms underlying acupuncture's preventive and therapeutic effects on brain disorders, and accelerating the pace of translational development in acupuncture medicine. This paper briefly outlines the current research status, challenges, and potential future directions in acupuncture treatment for brain disorders, aiming to provide essential insights for the modernization and development of acupuncture in the treatment of brain disorders.
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Terapia por Acupuntura , Encefalopatías , Humanos , Encefalopatías/terapiaRESUMEN
BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Hemostáticos , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Pronóstico , Neoplasias Esofágicas/patología , Fibrinógeno , Linfocitos/patología , Biomarcadores , Neutrófilos/patología , Estudios RetrospectivosRESUMEN
Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
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Gastritis , Neoplasias Gástricas , Infecciones Estreptocócicas , Streptococcus anginosus , Animales , Humanos , Ratones , Atrofia/patología , Carcinogénesis , Transformación Celular Neoplásica , Mucosa Gástrica , Gastritis/patología , Inflamación/patología , Proteínas Quinasas Activadas por Mitógenos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Streptococcus anginosus/fisiología , Infecciones Estreptocócicas/patologíaRESUMEN
Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.
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Terapia por Acupuntura , Acupuntura , Encefalopatías , Moxibustión , Humanos , Encefalopatías/diagnóstico por imagen , Encefalopatías/terapia , NeuroimagenRESUMEN
Background: There are multiple recommendations on the third-line therapy of metastatic colorectal cancer (mCRC); however, no consensus has been reached. Objectives: This study aimed to explore the patient demographics and the real-world third-line treatment landscape of mCRC. Design: A retrospective real-world cohort study. Methods: Electronic medical records of mCRC patients from Tianjin Medical University Cancer Institute and Hospital between 2013 and 2020 were collected. Upon descriptive, comparative, and survival analyses, a retrospective study was conducted to describe demographics and clinical outcomes of mCRC patients receiving third-line treatment. Results: Among 218 mCRC patients receiving third-line therapy, 65.5% received chemotherapy combined with or without targeted drugs, followed by anti-angiogenic monotherapy (18.4%), anti-epidermal growth factor receptor drugs (6.9%) and immunotherapy (6.4%). The overall response rate and disease control rate reached 10.2% and 59.2%, respectively; and median progression-free survival (PFS) and overall survival were 4.0 m and 10.7 m, respectively. After Cox multivariate analysis, we found that therapeutic regime was an independent prognostic factor. Compared to patients receiving anti-angiogenic monotherapy, those receiving chemotherapy combined with or without targeted drugs exhibited better prognosis. For patients whose PFS were longer in the front-line treatment, the PFS of third-line therapy was also relatively longer (p = 0.023). Multiple types of therapies (>3, p = 0.002) or multiple drugs (>5, p = 0.024) in the whole-course management of mCRC are indicators of longer survival. Conclusion: Chemotherapy combined with or without targeted therapy remained dominated third-line choice and showed favorable efficacy compared with anti-angiogenic monotherapy. With the application of more types and quantities of effective drugs, patients would achieve better survival.
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Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of 13C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by 13C-inulin. Integration of 13C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología , Inulina , Ácidos Grasos/metabolismo , Inflamación , Fibras de la DietaRESUMEN
Background: The KEYNOTE-811 study exhibited promising preliminary results for HER2-positive metastasis gastric adenocarcinoma; however, long-term survival benefit remains to be determined. Methods: In this single-center, controlled, retrospective study, patients with histologically confirmed HER2-positive unresectable or metastatic gastric/gastroesophageal adenocarcinoma received either anti-PD-1 antibody combined with trastuzumab and chemotherapy (cohort A) or trastuzumab and chemotherapy treatment (cohort B). The primary end points were progression-free survival (PFS) and overall survival (OS). The secondary end points were objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). Results: A total of 56 patients were eligible to join the study, with 30 patients in cohort A and 26 patients in cohort B. The median PFS (mPFS) was 16.2 months (95% CI, 15.093-17.307) in cohort A versus 14.5 months (95% CI, 9.491-19.509) in cohort B (p = 0.58). The median OS in cohort A was 28.1 months (95% CI, 17.625-38.575) versus 31.6 months (95% CI, 13.757-49.443) in cohort B (p = 0.534). ORRs were 66.7% and 50% in the two groups, respectively. DCRs were 90% and 84.6% in the two groups. Median DoR was not reached in cohort A and it was 16.3 (95% CI, 8.453-24.207) months in cohort B (p = 0.141). The most common irAEs were grade 1 hypothyroidism (33.3%) in cohort A. No treatment-related deaths occurred in this study. Conclusions: This retrospective cohort study provided a preliminary picture on the long-term follow-up of combining anti-PD-1 antibody with trastuzumab and chemotherapy in HER2-positive GC, and a trend with longer DoR and ORR was identified. Further studies with larger sample sizes and more in-depth molecular investigation are needed.
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BACKGROUND: The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. METHODS: In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator's choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. RESULTS: From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9-72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4-11.5) and 12.5 months (95% CI, 3.7-21.3), respectively. Grade 3-4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3-4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. CONCLUSION: Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05025033, 27/08/2021.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudios Prospectivos , Unión EsofagogástricaRESUMEN
Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research.
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The common development of multi-disciplinary intersection is a hot spot in the research of acupuncture- moxibustion translational medicine. This article analyzes the current situation and reasons for slow development of acupuncture-moxibustion translational medicine, takes acupuncture-moxibustion for depressive disorder as an example, takes acupuncture and moxibustion literature, clinical evidence-based, biological mechanism and medical equipment research and development as the main line, expounds potential strategies to promote the development of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation, and discusses the future research direction of acupuncture-moxibustion translational medicine.
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Ciencia Traslacional BiomédicaRESUMEN
Objectives: To analyze diabetes mellitus (DM) mortality and years of life lost (YLL) in different years and different subgroups at the national and regional levels in China from 2005 to 2020. Methods: We estimated mortality and YLL of DM and its subcategories for 31 provinces in China during 2005-2020 using multisource data from the National Mortality Surveillance System (NMSS). Results: The age standardized mortality rate (ASMR) of DM increased from 12.18 per 100,000 in 2005 to 13.62 per 100,000 in 2020, which was an increase of 11.86%. The ASMR of type 2 diabetes mellitus (T2DM) was much higher than that of type 1 diabetes mellitus (T1DM). The ASMR of T1DM remained stable, but the rate of T2DM increased, and the increase in male patients was higher than that in their female counterparts. At the same time, the burden of premature death was highest in the group ≥ 80 years old, and ASMR increased from 236.02 per 100,000 in 2005 to 358.86 per 100,000 in 2020. In 2005, the eastern region had the highest ASMR of DM, but the western region's ASMR grew faster and eventually became the highest in 2020. In addition, the YLL rate in the eastern region showed a downward trend; however, in the middle and western regions the YLL rate continued to rise, with that of the western region rapidly increasing. Conclusion: A dramatically upward trend in DM deaths can be seen in China from 2005 to 2020. DM remains a chronic disease in urgent need of prevention and control, especially in the elderly and people in less-affluent provinces. We must put forward more targeted policies to effectively allocate medical resources and focus on high-risk groups to reduce the premature-mortality burden of DM and its subcategories.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Anciano , Anciano de 80 o más Años , China/epidemiología , Enfermedad Crónica , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , MasculinoRESUMEN
Background: Cardiovascular disease (CVD) is the leading cause of death (COD) in China. Understanding the characteristics of place of death (POD) among CVD deaths would be of great importance to evaluate the healthcare service utilization at the end stage of life. Limited studies have reported the POD distribution among CVD deaths, and little was known about the associated factors of hospital CVD deaths. Methods: By using data from National Mortality Surveillance System (NMSS) in China, this study presented the characteristics of POD distribution during 2008 and 2020. Afterwards, multilevel logistic regression was used to explore associated factors of hospital CVD deaths and quantify the magnitude to which the spatial variations of hospital CVD deaths could be explained by those associated factors. Findings: During 2008-2020, there was 7101871 CVD deaths collected by NMSS in China, with 77·13% home deaths and 18·49% hospital deaths. Shanghai (59·40%) had the highest percentage of hospital CVD deaths. Age, sex, ethnicity, marital status, education, occupation, underlying COD were significant influential factors of hospital CVD deaths. Spatial variations were shown at provincial level, with 33·88% of them being explained by factors at individual level. Interpretation: Home was the leading POD among CVD deaths in China, those CVD decedents characterized as the female, the youngest, Han population, the married, the retiree, lived in urban areas, with higher socioeconomic status and died of chronic CVDs had a higher probability of hospital deaths. Providing accessible and available healthcare services were priorities to improve quality of end-of-life care, significant variations among provinces and sub-population also reminded us of the requirements for equal healthcare resources allocation and multiple options for minorities of POD preference at the end stage of life. Funding: National Key Research & Development Program of China (grant number 2018YFC1315301).
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A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical findings that orally given L-DOPA can alleviate or even prevent akinesia gave great hope for the treatment of PD. Attention focused on the role of tyrosine hydroxylase (TH) as the rate-limiting enzyme in the formation of catecholamines. It became evident that the enzyme driven formation is lowered in PD. Such results could only be obtained from studying human brain samples demonstrating the necessity for human brain banks. Originally, a TH enzyme deficiency was suspected in PD. Studies were conducted on the enzyme properties: its induction and turnover, the complex regulation starting with cofactor requirements as tetrahydrobiopterin and ferrous iron, and the necessity for phosphorylation for activity as well as inhibition by toxins or regulatory feedback inhibition by catecholamines. In the course of time, it became evident that neurodegeneration and cell death of dopaminergic neurons is the actual pathological process and the decrease of TH a cophenomenon. Nevertheless, TH immunochemistry has ever since been a valuable tool to study neuronal pathways, neurodegeneration in various animal models of neurotoxicity and cell cultures, which have been used as well to test potential neuroprotective strategies.
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Enfermedad de Parkinson , Tirosina 3-Monooxigenasa , Animales , Catecolaminas/metabolismo , Neuronas Dopaminérgicas/metabolismo , Levodopa , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer's disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid ß (Aß) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.
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To examine the trends of nasopharyngeal carcinoma (NPC) mortality and years of life lost (YLL) in China and its provinces from 2005 to 2020, our study used data from China National Mortality Surveillance System (NMSS) to estimate the number and rate of mortality and YLL of NPC by age and sex. We calculated average annual percent change (AAPC) to describe the trend of NPC mortality and YLL over time. We also analyzed the proportion of NPC deaths in all cancer deaths and explored the drivers of change in NPC deaths by decomposition analysis. The age-standardized mortality rate (ASMR) of NPC in China had a significant downward trend from 2.0/100 000 in 2005 to 1.4/100 000 in 2020 (AAPC = -2.4, P < .05). Age-standardized YLL rate also showed the similar trends (AAPC = -2.8, P < .05). Southern provinces including Guangdong (163.9/100 000), Guangxi (130.5/100 000), and Hainan (105.6/100 000) had the highest YLL rate in 2020. The mortality and YLL rate increased with age and males were higher than females. From 2005 to 2020, the proportion of NPC deaths in all cancer deaths remained stable at around 1.0% in China. The total number of deaths of NPC increased by 7.3%, of which age-specific mortality, population growth, and population aging accounted for -46.2%, 8.5% and 45.0%, respectively. NPC remains a significant public health issue in China southern provinces and tailored prevention and control strategies should be strengthened to reduce the burden of premature mortality of NPC in high risk areas.