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2.
Front Pharmacol ; 15: 1389383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011502
4.
Thorac Cancer ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031011

RESUMO

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

5.
J Clin Ultrasound ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041232

RESUMO

Sarcoid myositis is a rare and often debilitating extrapulmonary manifestation of sarcoidosis that can be difficult to recognize without a prior sarcoidosis diagnosis. Sarcoidosis with muscle nodules or masses as the first symptom is the least common form, occurring in approximately 0.5%-2.3% of cases. This article presents four middle-aged female patients who initially sought medical attention for a lower limb mass. Ultrasound examinations revealed consistent characteristic changes indicative of myositis. All patients underwent ultrasound-guided muscle biopsy and were diagnosed with sarcoidosis. Therefore, ultrasonography plays a pivotal role as the primary diagnostic tool for the early detection of sarcoid myositis.

6.
PNAS Nexus ; 3(7): pgae281, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39045014

RESUMO

Elucidating kinase-substrate relationships is pivotal for deciphering cellular signaling mechanisms, yet it remains challenging due to the complexity of kinase networks. Herein, we report the development of a versatile DNA-based kinase assay platform for high-throughput profiling of plant protein kinase activities and substrate preferences. Our approach employs DNA-linked peptide substrates, facilitating quantitative and specific kinase activity detection through next-generation DNA sequencing. Leveraging DNA barcodes as quantitative readouts, our approach establishes a high-throughput, sensitive, and specific platform for dissecting kinase-substrate networks in plants, representing a powerful tool for elucidating signaling mechanisms in plants.

7.
Curr Issues Mol Biol ; 46(6): 5881-5893, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38921022

RESUMO

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.

8.
World Neurosurg ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878889

RESUMO

OBJECTIVE: Acute rupture and hemorrhage of pediatric brain arteriovenous malformations (AVMs) may lead to cerebral herniation or intractable intracranial hypertension, necessitating emerging surgical interventions to alleviate intracranial pressure. However, there is still controversy regarding the timing of treatment for ruptured AVMs. This study aimed to assess the feasibility of utilizing three-pillar expansive craniotomy (3PEC) at different times during the treatment of pediatric ruptured supratentorial AVMs. METHODS: A retrospective analysis was conducted on all consecutive cases of acute rupture in supratentorial AVM children who underwent 3PEC at a single institution from 2020 to 2022. General information, clinical characteristics, radiological data, and prognosis were reviewed and analyzed. RESULTS: Thirteen children were included in the analysis. The intracranial pressure of all patients decreased to below 15 mmHg within 10 days. The expansion volume of the cranial cavity of the patients increased by 18.3 cm3 (95% confidence interval, 10.2-26.3; P < 0.001) compared to the hematoma volume. None of the patients required decompressive craniectomy due to intractable intracranial hypertension caused by cerebral swelling. The median waiting period for patients with delayed AVMs treatment was 8 days, during which no rebleeding occurred. CONCLUSIONS: Emergency intervention with 3PEC in children experiencing acutely ruptured supratentorial AVMs appears to be feasible. For children requiring delayed management of the AVMs, 3PEC may diminish the risk of rebleeding during the waiting period and shorten the waiting period.

9.
Children (Basel) ; 11(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38929304

RESUMO

Pediatric heart failure (HF) is associated with high readmission rates, but the optimal serum potassium range for this population remains unclear. In this single-center retrospective cohort study, 180 pediatric patients hospitalized for HF between January 2016 and January 2022 were stratified into low-potassium (<3.7 mmol/L), middle-potassium (3.7-4.7 mmol/L), and high-potassium (≥4.7 mmol/L) groups based on the distribution of potassium levels in the study population. The primary outcome was readmission for HF within 1 year of discharge. Cox regression and restricted cubic spline models were used to assess the association between potassium levels and 1-year HF readmission rates. Notably, 38.9% of patients underwent 1 or more 1-year readmissions for HF within 1 year. The high-potassium group had a significantly higher readmission frequency than the middle-potassium group. In multivariate Cox regression models, potassium levels of ≥4.7 mmol/L were independently associated with increased 1-year readmission risk. A J-shaped relationship was observed between baseline potassium levels and 1-year readmission risk, with the lowest risk at 4.1 mmol/L. In pediatric patients with HF, a serum potassium level ≥ 4.7 mmol/L was independently associated with increased 1-year readmission risk. Maintaining potassium levels within a narrow range may improve outcomes in this population.

10.
Biol Methods Protoc ; 9(1): bpae039, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884001

RESUMO

Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)-protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated.

11.
Int J Oral Sci ; 16(1): 47, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38945975

RESUMO

Dysregulated Epiregulin (EREG) can activate epidermal growth factor receptor (EGFR) and promote tumor progression in head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underlying EREG dysregulation remain largely unknown. Here, we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues. Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway. Of note, we found that N-glycosylation of EREG was essential for its stability, membrane location, biological function, and upregulation of its downstream target PDL1 in HNSCC. EREG was glycosylated at N47 via STT3B glycosyltransferases, whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG. Consistently, knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells. Moreover, treatment of HNSCC cells with NGI-1, an inhibitor of STT3B, blocked STT3B-mediated glycosylation of EREG, leading to its degradation and suppression of PDL1. Finally, combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo. Taken together, STT3B-mediated N-glycosylation is essential for stabilization of EREG, which mediates PDL1 upregulation and immune evasion in HNSCC.


Assuntos
Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Regulação para Cima , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Western Blotting , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Epirregulina , Glicosilação , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Evasão da Resposta Imune , Sialiltransferases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
12.
Sci Adv ; 10(25): eado5179, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896610

RESUMO

Surface air temperature (SAT) is a key indicator of climate change. Variations in cloud cover affect SAT by interacting with radiation. During daytime, clouds tend to cool the surface by blocking sunlight, while nighttime clouds warm the surface by trapping longwave radiation. Here, we show that, on the global scale, cloud cover, particularly low-level cloudiness, exhibits diurnally asymmetric trends in a warming climate. Cloud fraction on average decreases more during the day than at night. Climate models indicate that the diurnally asymmetric cloud cover variation is mainly driven by trends in the lower tropospheric stability and is largely attributed to the increasing greenhouse gases rather than natural variability. This asymmetry, therefore, turns out to be an amplifier of surface warming, by both decreasing the daytime cloud shortwave albedo effect and increasing the nighttime cloud longwave greenhouse effect.

13.
Sci Total Environ ; 946: 174127, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38908574

RESUMO

Black carbon (BC), as a critical light-absorbing constituent within aerosols, exerts profound effects on atmospheric radiation balance, climate, air quality and human health, etc. And it is also a long-standing focus in rapidly developing megacities. So, this study primarily focuses on investigating the variation characteristics and underlying causes of BC in Chongqing (31,914,300 population), which is one of the municipalities directly under the central government of China, serving as a pivotal economic hub in southwest China. Utilizing MERRA-2 reanalysis data, we examined the long-term changes of atmospheric BC over Chongqing 20 years (from 2002 to 2021). Moreover, BC mass concentration observations were conducted using an Aethalometer (AE-33) from March 15 to June 14, 2021 in Liangping District, Chongqing. The statistical analysis over the last 20 years reveals an annual mean BC concentration in Chongqing of 3.42 ± 0.20 µg/m3, exhibiting growth from 2002 to 2008, followed by a decline from 2008 to 2021. Monthly concentration displays a "U-shaped" trend, with the lowest values occurring in summer and the highest in winter. Due to topographical and meteorological influences, local emissions primarily contribute to BC pollution, characterized by a spatial distribution pattern of high in the west and low in the east. Ground observation indicates a distinct dual-peaked pattern in the diurnal variation of BC, with peak concentrations aligning with periods of high traffic emissions. The variation in BC is significantly influenced by meteorological conditions (wind, temperature, atmospheric boundary layer) and local pollution sources (predominantly traffic). Furthermore, extreme events analysis suggests that local emissions and regional transport (with higher contributions from Chongqing and the Sichuan Basin) predominantly contributed to BC pollution. This study effectively makes up for the deficiency in analyzing the distribution and sources of BC pollution in Chongqing, providing valuable scientific insights for the atmospheric environment of megacities.

14.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167225, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38749218

RESUMO

BACKGROUND: Acute kidney injury (AKI) causes distant liver injury, to date, which causes poor outcomes of patients with AKI. Many studies have been performed to overcome AKI-associated liver injury. However, those studies have mainly focused on hepatocytes, and AKI-induced liver injury still remains a clinical problem. Here, we investigated the implication of cholangiocytes and their primary cilia which are critical in final bile secretion. Cholangiocyte, a lining cell of bile ducts, are the only liver epithelial cell containing primary cilium (a microtubule-based cell surface signal-sensing organelle). METHODS: Cystathione γ-lyase (CSE, a transsulfuration enzyme) deficient and wild-type mice were subjected to kidney ischemia followed by reperfusion (KIR). Some mice were administered with N-acetyl-cysteine (NAC). RESULTS: KIR damaged hepatocytes and cholagiocytes, disrupted cholangiocytes primary cilia, released the disrupted ciliary fragments into the bile, and caused abnormal bile secretion. Glutathione (GSH) and H2S levels in the livers were significantly reduced by KIR, resulting in increased the ratio oxidized GSH to total GSH, and oxidation of tissue and bile. CSE and cystathione ß-synthase (CBS) expression were lowered in the liver after KIR. NAC administration increased total GSH and H2S levels in the liver and attenuated KIR-induced liver injuries. In contrast, Cse deletion caused the reduction of total GSH levels and worsened KIR-induced liver injuries, including primary cilia damage and abnormal bile secretion. CONCLUSIONS: These results indicate that KIR causes cholangiocyte damage, cholangiocytes primary cilia disruption, and abnormal bile secretion through reduced antioxidative ability of the liver.


Assuntos
Bile , Cílios , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Cílios/metabolismo , Cílios/patologia , Camundongos , Bile/metabolismo , Masculino , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Camundongos Endogâmicos C57BL , Glutationa/metabolismo , Camundongos Knockout , Fígado/patologia , Fígado/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Cistationina gama-Liase/metabolismo , Cistationina gama-Liase/genética , Rim/metabolismo , Rim/patologia , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Ductos Biliares/patologia , Ductos Biliares/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia
15.
Adv Healthc Mater ; : e2400501, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38817106

RESUMO

In response to the increasing demand for spheroid-based cancer research, the importance of developing integrated platforms that can simultaneously facilitate high-throughput spheroid production and multiplexed analysis is emphasized. In addition, the understanding of how the size and cellular composition of tumors directly influence their internal structures and functionalities underlines the critical need to produce spheroids of diverse sizes and compositions on a large scale. To address this rising demand, this work presents a configurable and linkable in vitro three-dimensional (3D) cell culture kit (CLiCK) for spheroids, termed CLiCK-Spheroid. This platform consists of three primary components: a hanging drop microarray (HDMA), a concave pillar microarray (CPMA), and gradient blocks. The HDMA alone produces a homogeneous spheroid array, while its combination with the gradient block enables one-step generation of a size-gradient spheroid array. Using the size-gradient spheroid arrays, the occurrence of necrotic cores based on spheroid size is demonstrated. Additionally, spheroids in a single batch can be conveniently compartmentalized and regrouped using a CPMA, enhancing the versatility of spheroid arrays and enabling multiplexed drug treatments. By combining the different assembly methods, this work has achieved high-throughput production of cell composition-gradient spheroid arrays, with noticeable variations in morphology and vascularization based on cell compositions.

16.
Chemphyschem ; : e202300838, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708615

RESUMO

The work function (WF) measurement plays a critical role in engineering energy materials and energy devices. However, the ultra-high vacuum (UHV) environments of photoemission method limit the practical application for absolute work function measurements of materials, especially under complex working conditions. To understand the energy level of materials under complex chemical environments, the in-situ measurements of work function is necessary in complex metal/semiconductor system for various application. In this paper, we describe the utilization of ambient pressure X-ray photoemission spectroscopy (APXPS) with utilization of low photon energy X-ray for absolute WF measurements at BL02B of the Shanghai Synchrotron Radiation Facility. We herein present the WF measurement during oxygen adsorption on Pt(111) and oxidation of Cu(111) in ambient oxygen environment as demonstration of the APXPS capability for WF measurement. After oxygen chemisorption on Pt and formation of Cu2O, the WF will increase. This is due to charge transfer from metal to chemisorbed oxygen atoms. After the formation of bulk Cu2O and CuO, the WF value almost remain at ~5.5 eV. We believe the direct measurement of absolute work function via APXPS could help bridge the gap between the physical properties and the surface chemical species for metal/semiconductor materials.

17.
BMC Med ; 22(1): 215, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38807144

RESUMO

BACKGROUND: Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. METHODS: The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494-0.957) and 51.6% (95% CI, 0.307-0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. CONCLUSIONS: Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. TRIAL REGISTRATION: ChiCTR2000031608.


Assuntos
Antineoplásicos , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Neoplasias de Cabeça e Pescoço , Melanoma , Piperidinas , Piridinas , Pirimidinas , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Amplificação de Genes , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Resultado do Tratamento , Piperidinas/efeitos adversos , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos
18.
BMC Neurol ; 24(1): 163, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769482

RESUMO

OBJECTIVE: Fibrinogen, essential in primary hemostasis, platelet aggregation, and leukocyte-endothelial interactions, is also associated with a heightened risk of acute ischemic stroke (AIS). However, its influence on AIS patient outcomes is unclear. This study examines the correlation between fibrinogen levels and the risk of unfavorable outcomes three months post-AIS. METHODS: This is a secondary analysis of a prospective cohort study conducted in Korea. The sample consisted of 1851 AIS patients who received treatment at a Korean hospital between January 2010 and December 2016. Statistical models were established to understand the relationship between fibrinogen levels(mg/dL) and unfavorable outcomes(mRs ≥ 3), including logistic regression models, Generalized Additive Models (GAM), and smooth curve fitting (penalized splines). The log-likelihood ratio test has been utilized to evaluate the best fit. To ensure the robustness of the results, sensitivity analyses were conducted by reanalyzing the relationship after excluding participants with TG > 200 mg/dl and BMI > 25 kg/m2. Subgroup analyses were also performed to assess whether influencing factors modify the association between fibrinogen levels and unfavorable outcomes. RESULTS: After adjusting for multiple covariates including age, BMI, sex, LDL-c, TG, HGB, HDL-c, BUN, FPG, ALB, PLT, AF, hypertension, smoking, DM, mRs score at admission, the binary logistic regression model demonstrated revealed a significant positive association between fibrinogen levels and the risk of unfavorable outcomes in AIS patients (OR = 1.215, 95% CI: 1.032-1.429, p = 0.019). Sensitivity analyses supported these findings, with similar ORs observed in subsets of patients with TG < 200 mg/dL (OR = 1.221, 95% CI: 1.036-1.440) and BMI < 25 kg/m2 (OR = 1.259, 95% CI: 1.051-1.509). Additionally, the relationship between fibrinogen levels and outcomes was nonlinear, with a critical threshold of 2.74 g/L. Below the inflection point, the OR for unfavorable outcomes was 0.666 ((95% CI: 0.360, 1.233, p = 0.196), whereas above it, the OR increased to 1.374 (95% CI: 1.138, 1.659). CONCLUSIONS: This study has provided evidence of a positive and nonlinear correlation between fibrinogen levels and 3-month poor functional outcomes in patients with AIS. When fibrinogen levels exceeded 2.74 g/L, a significant and positive association was observed with the risk of poor outcomes. This study provides a further reference for optimizing rehabilitation exercises and facilitating clinical counseling in patients with acute ischemic stroke.


Assuntos
Fibrinogênio , AVC Isquêmico , Humanos , Feminino , Fibrinogênio/análise , Fibrinogênio/metabolismo , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Prognóstico , Estudos de Coortes , República da Coreia/epidemiologia , Dinâmica não Linear
19.
Front Endocrinol (Lausanne) ; 15: 1310223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706697

RESUMO

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy. Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases. Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders. Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.


Assuntos
Antieméticos , Radioisótopos do Iodo , Náusea , Neoplasias da Glândula Tireoide , Vômito , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antieméticos/uso terapêutico , Antieméticos/administração & dosagem , Adulto , Radioisótopos do Iodo/uso terapêutico , Radioisótopos do Iodo/efeitos adversos , Idoso , Vômito/prevenção & controle , Vômito/etiologia , Náusea/prevenção & controle , Náusea/etiologia , Adulto Jovem , Adolescente , Neoplasias da Glândula Tireoide/radioterapia , Ondansetron/uso terapêutico , Ondansetron/administração & dosagem , Qualidade de Vida
20.
bioRxiv ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38746393

RESUMO

Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealed Prokr2 in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2R LPO neurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2R LPO →PBN circuit or the postsynaptic PROKR2 PBN neurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2 PBN neurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.

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