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1.
Artigo em Inglês | MEDLINE | ID: mdl-38779753

RESUMO

17ß-hydroxysteroid dehydrogenase-13 (HSD17B13), a newly identified lipid droplet-associated protein, plays an important role in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Emerging evidence demonstrates that NASH is an independent risk factor for chronic kidney disease (CKD), which is frequently accompanied by renal lipid accumulation. In addition, the HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven NAFLD. At present, the role of HSD17B13 in lipid accumulation in the kidney is unclear. ​This study utilized bioinformatic and immunostaining approaches to examine the expression and localization of HSD17B13 along mouse urinary tract. We found that HSD17B13 is constitutively expressed in the kidney, ureter and urinary bladder. Our findings reveal for the first time the precise localization of HSD17B13 in mouse urinary system, providing a basis for further studying the pathogenesis of HSD17B13 in various renal and urological diseases.

2.
Sci Signal ; 17(836): eadd5073, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743809

RESUMO

The Ras-mitogen-activated protein kinase (MAPK) pathway is a major target for cancer treatment. To better understand the genetic pathways that modulate cancer cell sensitivity to MAPK pathway inhibitors, we performed a CRISPR knockout screen with MAPK pathway inhibitors on a colorectal cancer (CRC) cell line carrying mutant KRAS. Genetic deletion of the catalytic subunit of protein phosphatase 6 (PP6), encoded by PPP6C, rendered KRAS- and BRAF-mutant CRC and BRAF-mutant melanoma cells more resistant to these inhibitors. In the absence of MAPK pathway inhibition, PPP6C deletion in CRC cells decreased cell proliferation in two-dimensional (2D) adherent cultures but accelerated the growth of tumor spheroids in 3D culture and tumor xenografts in vivo. PPP6C deletion enhanced the activation of nuclear factor κB (NF-κB) signaling in CRC and melanoma cells and circumvented the cell cycle arrest and decreased cyclin D1 abundance induced by MAPK pathway blockade in CRC cells. Inhibiting NF-κB activity by genetic and pharmacological means restored the sensitivity of PPP6C-deficient cells to MAPK pathway inhibition in CRC and melanoma cells in vitro and in CRC cells in vivo. Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6-NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells.


Assuntos
Sistema de Sinalização das MAP Quinases , NF-kappa B , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , NF-kappa B/metabolismo , NF-kappa B/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Mutação , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Melanoma/genética , Melanoma/metabolismo , Melanoma/tratamento farmacológico , Melanoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos Nus
3.
Sci Total Environ ; 933: 173138, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734107

RESUMO

Due to the similar sources of swage irrigation, organic fertilizer, and sludge application, microplastics (MPs) and antibiotics coexist inevitably in the agriculture soils. However, the impacts of MPs with different polymer types and aging status on the bio-accessibility of co-existing antibiotics in soils remained unclear. Therefore, we using the diffusive gradients films for organic compounds devices (o-DGT) to evaluated the distribution of sulfadiazine (SDZ) in both paddy soil and saline soil amended with 0.5 % (w/w) MPs. Four polymer types (polyethylene: PE, polypropylene: PP, polyamide: PA, and polyethylene terephthalate: PET) and two aging statuses (aged PE and aged PP) of MPs were used in this study. Results showed that soil properties significantly influence the partition of SDZ in soil and soil solution, and SDZ gained a lower degradation rate but higher mobility in saline soil. MPs pose different impacts on partition of SDZ between paddy soil and saline soil. Notably, PP reduced the labile solid phase-solution phase partition coefficient (Kdl) by 17.7 % in paddy soil, while PE, PP, and aPE increased the Kdl value by 2.00, 1.62, and 2.81 times in saline soil. Besides, in saline soil, all the MPs reduced the SDZ concentration in the soil solution, while significantly increased the SDZ in o-DGT phase. Conversely, MPs did not impact the SDZ's o-DGT concentration in paddy soil. Additionally, MPs increased the R value of SDZ in two soils, especially in saline soil. It suggested that MPs could potentially enhance the resupply of SDZ from soil to plants, particularly under saline conditions. Furthermore, aged MPs had a more pronounced effect on these indicators compared to virgin MPs in saline soil. Therefore, MPs in soil poses a potential risk for biota's uptake of SDZ, particularly in fragile environment. Moreover, the risk intensifies with aged MPs.

4.
Circulation ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587333

RESUMO

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

5.
Oncologist ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642091

RESUMO

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38649640

RESUMO

BACKGROUND: Simultaneous transcatheter mitral valve in valve (VIV) replacement and aortic valve replacement experience is limited. We report our initial experience with simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction. METHODS: A total of 8 patients had simultaneous transcatheter heart valve implants for severe mitral bioprosthesis failure (VIV), with a second valve procedure that included native aortic regurgitation (n = 3) or degenerated bioprostheses in the aortic position (n = 5). All patients were treated with a self-expandable J-valve transcatheter valve, using the transapical approach. RESULTS: The mean age of the patients was 73.1 ± 6.2 years. The mean Society of Thoracic Surgeons score was 13.8 ± 6.3%. Device success was 100% according to Valve Academic Research Consortium-2 criteria. No other procedure-associated complications occurred, including left ventricular outflow tract obstruction and valve migration. The mean hospital lengths of stay after the procedure were 11.5 ± 8.0 days. No deaths occurred at 30 days. At a median follow-up period of 28.7 ± 22.3 months, no patients died. All patients were in New York Heart Association functional classes I-II. Echocardiographic parameters at follow-up showed a normofunctioning J valve in the mitral position and a mean max mitral flow velocity of 2.0 ± 0.5 m/s; the J valve in the aortic position was also normofunctioning, and the mean max aortic flow velocity was 2.3 ± 0.5 m/s. CONCLUSION: Simultaneous transapical transcatheter aortic and mitral valve replacement using the self-expandable J valve appears to be a feasible and effective alternative to redo surgery.

7.
Polymers (Basel) ; 16(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611153

RESUMO

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

8.
Transl Cancer Res ; 13(3): 1382-1393, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617513

RESUMO

Background: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Thus, this study aimed to identify a prognostic molecular signature to predict the overall survival (OS) of patients with EAC. Methods: The mRNA microarray data sets GSE13898 and GSE26886 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing profile and clinical data of EAC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between EAC tissues and adjacent non-cancerous tissues were obtained using R software. DEGs associated with prognosis of OS were assessed by univariate Cox analysis, and a prognostic signature was built using stepwise multivariate Cox analysis. Time-dependent receiver operating characteristic (ROC) analysis and stratification analysis were conducted to evaluate its predictive performance. Functional enrichment analysis was performed for genes co-expressed with the signature to explore its biological functions in EAC. Results: A total of 336 genes were identified to be differentially expressed between EAC tissues and adjacent non-cancerous tissues. After univariate and multivariate Cox regression analysis, four genes (ALAD, ABLIM3, IL17RB and IFI6) were screened out to construct a prognostic signature. According to this signature, patients could be assigned into high-risk and low-risk group with significantly different OS (P=4.92e-05<0.0001). Multivariate Cox regression analysis suggested that the four-gene signature served as an independent factor in OS prediction. In the time-dependent ROC analysis, the areas under the curves (AUCs) were 0.804, 0.792 and 0.695 for 1-, 3- and 5-year survival prediction, respectively, suggesting a good performance. Functional enrichment analysis showed that the signature was mainly clustered in cell proliferation related biological processes or pathways. Conclusions: The four-gene signature identified in the current study may be a potential prognostic factor for predicting OS of EAC patients.

9.
Ital J Pediatr ; 50(1): 74, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637856

RESUMO

BACKGROUND: Plastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS. METHODS: We conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021. RESULTS: A total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression. CONCLUSIONS: Children with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.


Assuntos
Bronquite , Cardiopatias Congênitas , Disfunção Ventricular Direita , Criança , Humanos , Estudos Retrospectivos , Bronquite/diagnóstico , Bronquite/tratamento farmacológico , Bronquite/etiologia , Broncoscopia , Corticosteroides , Cardiopatias Congênitas/cirurgia
10.
Mikrochim Acta ; 191(5): 246, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38580781

RESUMO

Heavy metal pollution has attracted global attention because of its high toxicity, non-biodegradability, and carcinogenicity. Electrochemical sensors are extensively employed for the detection of low concentrations of heavy metal ions (HMIs). However, their applicability is often limited to the detection of ions that exhibit electrochemical signals exclusively in aqueous solutions. In this study, we proposed a multi-responsive detection platform based on the modification of horseradish peroxidase@zeolitic imidazolate frameworks-8/thionine/gold/ionic liquid-reduced graphene oxide (HRP@ZIF-8/THI/Au/IL-rGO). This platform demonstrated its capability to detect various metal ions, including those without conventional electrochemical signals. The Au/IL-rGO composite structure enhanced the specific surface area available for the reaction. Furthermore, the in situ growth of HRP@ZIF-8 not only shielded the THI signal prior to detection but also protected the electrode material. It was important to note that the introduced edetate disodium dihydrate (EDTA) had the ability to complex with various HMIs. When excess EDTA was present, it could cleave ZIF-8 and release HRP. In the presence of hydrogen peroxide (H2O2), HRP promoted the oxidation of THI previously reduced by the electrode and thus showed excellent sensitivity for HMIs detection. The proposed method overcame the limitation of traditional electrochemical sensors, which solely relied on electrochemical signals for detecting metal ions. This offers a novel approach to enhance electrochemical ion sensing detection.

11.
Cell Death Dis ; 15(4): 291, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658569

RESUMO

Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.


Assuntos
Anexina A2 , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Serina-Treonina Quinases TOR/metabolismo , Anexina A2/metabolismo , Anexina A2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Camundongos Nus , Camundongos , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Movimento Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Masculino , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Regulação Neoplásica da Expressão Gênica , Feminino
12.
Gynecol Obstet Invest ; : 1-13, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615670

RESUMO

INTRODUCTION: DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently methylated genes among patients with ovarian cancer. Therefore, our study aimed to better determine the prognostic and cancer characteristics effects of RASSF1A, BRCA1, APC, and p16 promoter methylation in ovarian cancer patients. METHODS: Databases such as PubMed, Web of Science, EMBASE, CNKI, and WanFang were searched for published studies up to March 4, 2024. The outcomes are shown as OR and HR with their 95% CIs. Then, the random or fixed-effect model was performed to evaluate the effect sizes. RESULTS: Finally, 27 articles were included in this meta-analysis. No significant relationships were observed between RASSF1A, BRCA1, and APC promoter methylation and the clinical prognostic (including overall survival and progression-free survival) and cancer characteristics (including ascites, lymph node metastasis, and pelvic peritoneal metastasis) in ovarian cancer. p16 promoter methylation was significantly related to poor progression-free survival (PFS) (HR = 1.52, 95% CI = 1.14-2.04) and overall survival (OS) (HR = 1.39, 95% CI = 1.06, to 1.83) in univariate and poor PFS in multivariate Cox regression models (HR = 1.42, 95% CI = 1.05-1.92). Besides, our results indicated that the clinical stage was associated with inferior OS while there was no significant association between tumor grade and OS. CONCLUSION: RASSF1A, BRCA1, and APC promoter methylation were not significantly associated with clinical prognostic and cancer characteristics. p16 may be a useful biomarker for predicting PFS in ovarian cancer. Furthermore, the clinical stage was significantly associated with OS. In further research, more prospective and multicenter validation studies remain needed.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38465434

RESUMO

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising outcomes as a second or subsequent-line treatment for human epidermal growth factor-2 (HER2)-positive advanced gastric or gastroesophageal junction cancer. CASE PRESENTATION: We reported a 49-year-old male patient with stage IV HER2-amplified gastric cancer. Despite extensive pretreatments, including first-line trastuzumab plus FOLFOX, second-- line trastuzumab plus FOLFOX, followed by traditional Chinese medicine, third-line nivolumab plus trastuzumab, fourth-line pyrotinib plus paclitaxel and five hepatic arterial chemoembolization procedures, and fifth-line pembrolizumab plus nab-paclitaxel and thoracic radiotherapy, the patient experienced disease progression. In April 2021, T-DXd was initiated as the sixth-line therapy in combination with radiotherapy for brain metastases. After one treatment cycle, the patient achieved a partial response. T-DXd was discontinued in August 2022 due to recurrent anemia attributed to cardiac stenosis-related bleeding. CONCLUSION: The condition of the patient remained stable until May 2023, indicating a progression-free survival of over 24 months. This case suggests that T-DXd may offer long-term clinical benefits in patients with HER2-amplified advanced gastric cancer with brain metastases.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38555240

RESUMO

BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications. METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set. CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.

15.
J Thorac Dis ; 16(2): 1730-1737, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505078

RESUMO

Background: Patients with tricuspid bioprosthetic structural valve degeneration (SVD) often present with right ventricular enlargement and severe dysfunction, which cause a higher risk for redo cardiac surgery. In 2019, our center innovated using the J-valve system for valve-in-valve (ViV) implantation to treat tricuspid bioprosthetic SVD. The purpose of this study was to summarize the clinical effect after 1-year follow-up. Case Description: From April 2019 to October 2019, two cases of tricuspid bioprosthetic dysfunction were treated with the J-valve system. Both patients were male, aged 46 and 67 years, respectively. The preoperative evaluation showed that the risk of conventional redo open heart surgery was high. The J-valve implantation was successful in both cases. One patient had slight valve displacement when the transporter was withdrawn during the operation, and a second J-valve was implanted in an ideal position. There was no death, no delayed valve displacement, and no readmission during the follow-up period of 12 months. In both cases, there was an absence of trace tricuspid regurgitation. After 6 months of anticoagulation with warfarin, the patients were converted to long-term aspirin treatment. Conclusions: The ViV technique with J-valve is feasible and effective in treating tricuspid bioprosthetic SVD in high-risk patients, avoiding cardiopulmonary bypass and conventional thoracotomy injury.

16.
Sci Total Environ ; 924: 171598, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461995

RESUMO

Understanding the source identification and distribution of heavy metal(loid)s in soil is essential for risk management. The sources of heavy metal(loid)s in farmland soil, especially in areas with rapid economic development, were complicated and need to be explored urgently. This study combined geographic information system (GIS) mapping, positive matrix factorization (PMF) model and cadmium (Cd) isotope fingerprinting methods to identify heavy metal(loid) sources in a typical town in the economically developed Yangtze River Delta region of China. Cd, As, Cu, Zn, Pb, Ni and Co in different samples were detected. The results showed that Cd was the most severely contaminated element, with an exceedance rate of 78.0 %. GIS mapping results indicated that the hotspot area was located in the northeastern area with prolonged operational histories of electroplating and non-ferrous metal smelting industries. The PMF model analysis also identified emissions from smelting and electroplating enterprises as the main sources of Cd in the soil, counted for 49.28 %, followed by traffic (25.66 %) and agricultural (25.06 %) sources. Through further isotopic analysis, it was found that in soil samples near the industrial park, the contribution of electroplating and non-ferrous metal smelting enterprises to cadmium pollution was significantly higher than other regions. The integrated use of various methodologies allows for precise analysis of sources and input pathways, offering valuable insights for future pollution control and soil remediation endeavors.

17.
J Ethnopharmacol ; 331: 118079, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513776

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

18.
Front Cardiovasc Med ; 11: 1360763, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433755

RESUMO

Background: The clinical prognosis of mitral valve surgery at morning, afternoon, and evening is not yet clear. The aim of the study is to investigate the impact of different time periods of surgery in the morning, afternoon and evening on the short-term and long-term results of mitral valve surgery. Methods: From January 2018 to December 2020, 947 patients with mitral valve surgery in our department were selected. These patients were divided into 3 groups according to the starting time of surgery. Morning group (operation start time 8:00-10:30, n = 231), afternoon group (operation start time 12:00-14:30, n = 543), and evening group (operation start time 17:30-20:00, n = 173). The short-term and long-term results of the three groups were compared. Results: There were no significant difference in the long-term mortality, long-term risk of stroke and reoperation. And there were no significant difference in in-hospital outcomes, including mortality, stroke, cardiopulmonary bypass time, aortic cross clamp time, mitral valve repair convert to mitral valve replacement, number of aortic cross clamp ≥2 times, unplanned secondary surgery during hospitalization (including thoracotomy hemostasis, thoracotomy exploration, redo mitral valve surgery, and debridement), intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, mechanical ventilation time, and intensive care unit length of stay. Conclusion: There is no significant difference in the risk of short-term and long-term survival and adverse events after mitral valve surgery at different time periods in the morning, afternoon, and evening. Mitral valve surgery at night is safe.

19.
Heliyon ; 10(4): e26572, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38434053

RESUMO

Hypoxic exercise is an effective intervention for obesity, because it promotes weight loss by regulating fatty acid (FA) metabolism. The regulation of peroxisome proliferator-activated receptor ß (PPARß) by miR-122 may be involved in this process, but the detailed mechanisms are unknown. In order to address this issue, we probed how miR-122 affected the expression of factors associated with FA metabolism in skeletal muscle of obese rats undergoing hypoxic training. By injecting adeno-associated virus 9 containing miR-122 overexpression vector or miR-122 inhibitor into skeletal muscles of rats with a 4-week hypoxic exercise regimen, the miR-122 expression level can be regulated. Body composition and blood lipid levels were analyzed, and PPARß, carnitine palmitoyltransferase 1b (CPT1b), acetylCoA carboxylase 2 (ACC2), and FA synthase (FAS) mRNA and protein levels were evaluated using quantitative reverse transcription quantitative PCR(RT-qPCR) and Western blot analysis. We found that miR-122 overexpression increased low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and decreased PPARß, ACC2, and FAS expression. Conversely, miR-122 inhibition decreased TG level, increased high-density lipoprotein cholesterol (HDL-C) level, and upregulated PPARß, ACC2, FAS, and CPT1b. These data indicated that the negative regulation of PPARß by miR-122 promotes FA metabolism by altering the levels of the factors related to FA metabolism in skeletal muscle of obese rat under hypoxic training, thus providing molecular-level insight into the beneficial effects of this intervention.

20.
Sci Rep ; 14(1): 5274, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438393

RESUMO

Hepatocellular carcinoma (HCC) remains a formidable malignancy that significantly impacts human health, and the early diagnosis of HCC holds paramount importance. Therefore, it is imperative to develop an efficacious signature for the early diagnosis of HCC. In this study, we aimed to develop early HCC predictors (eHCC-pred) using machine learning-based methods and compare their performance with existing methods. The enhancements and advancements of eHCC-pred encompassed the following: (i) utilization of a substantial number of samples, including an increased representation of cirrhosis tissues without HCC (CwoHCC) samples for model training and augmented numbers of HCC and CwoHCC samples for model validation; (ii) incorporation of two feature selection methods, namely minimum redundancy maximum relevance and maximum relevance maximum distance, along with the inclusion of eight machine learning-based methods; (iii) improvement in the accuracy of early HCC identification, elevating it from 78.15 to 97% using identical independent datasets; and (iv) establishment of a user-friendly web server. The eHCC-pred is freely accessible at http://www.dulab.com.cn/eHCC-pred/ . Our approach, eHCC-pred, is anticipated to be robustly employed at the individual level for facilitating early HCC diagnosis in clinical practice, surpassing currently available state-of-the-art techniques.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Diagnóstico Precoce , Cirrose Hepática , Aprendizado de Máquina , Prednisona
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