RESUMO
Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.
Assuntos
Medicamentos de Ervas Chinesas , Doença Cardiopulmonar , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Doença Cardiopulmonar/tratamento farmacológico , Doença Cardiopulmonar/fisiopatologia , Doença Crônica/tratamento farmacológico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos sem Prescrição/uso terapêuticoRESUMO
Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.
Assuntos
Cálcio , Hipercalciúria , MicroRNAs , Nefrolitíase , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Humanos , Hipercalciúria/genética , Hipercalciúria/metabolismo , Hipercalciúria/patologia , Cálcio/metabolismo , Camundongos , Ratos , Nefrolitíase/metabolismo , Nefrolitíase/genética , Nefrolitíase/patologia , Masculino , Camundongos Endogâmicos C57BL , Cálculos Renais/metabolismo , Cálculos Renais/genética , Ratos Sprague-Dawley , Exossomos/metabolismo , Exossomos/genética , Feminino , Rim/metabolismo , Rim/patologia , Camundongos Knockout , Transdução de SinaisRESUMO
BACKGROUND: It is not fully established whether plasma ß-amyloid(Aß)42/Aß40 and phosphorylated Tau181 (p-Tau181) can effectively detect Alzheimer's disease (AD) pathophysiology in older Chinese adults and how these biomarkers correlate with astrocyte reactivity, Aß plaque deposition, tau tangle aggregation, and neurodegeneration. METHODS: We recruited 470 older adults and analyzed plasma Aß42/Aß40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, and 70 underwent magnetic resonance imaging, Aß and tau positron emission tomography imaging. The plasma Aß42/Aß40 and p-Tau181 thresholds were defined as ≤0.0609 and ≥2.418 based on the receiver operating characteristic curve analysis using the Youden index by comparing Aß-PET negative cognitively unimpaired individuals and Aß-PET positive cognitively impaired patients. To evaluate the feasibility of using plasma Aß42/Aß40 (A) and p-Tau181 (T) to detect AD and understand how astrocyte reactivity affects this process, we compared plasma GFAP, Aß plaque, tau tangle, plasma NfL, hippocampal volume, and temporal-metaROI cortical thickness between different plasma A/T profiles and explored their relations with each other using general linear models, including age, sex, APOE-ε4, and diagnosis as covariates. RESULTS: Plasma A+/T + individuals showed the highest levels of astrocyte reactivity, Aß plaque, tau tangle, and axonal degeneration, and the lowest hippocampal volume and temporal-metaROI cortical thickness. Lower plasma Aß42/Aß40 and higher plasma p-Tau181 were independently and synergistically correlated with higher plasma GFAP and Aß plaque. Elevated plasma p-Tau181 and GFAP concentrations were directly and interactively associated with more tau tangle formation. Regarding neurodegeneration, higher plasma p-Tau181 and GFAP concentrations strongly correlated with more axonal degeneration, as measured by plasma NfL, and lower plasma Aß42/Aß40 and higher plasma p-Tau181 were related to greater hippocampal atrophy. Higher plasma GFAP levels were associated with thinner cortical thickness and significantly interacted with lower plasma Aß42/Aß40 and higher plasma p-Tau181 in predicting more temporal-metaROI cortical thinning. Voxel-wise imaging analysis confirmed these findings. DISCUSSION: This study provides a valuable reference for using plasma biomarkers to detect AD in the Chinese community population and offers novel insights into how astrocyte reactivity contributes to AD progression, highlighting the importance of targeting reactive astrogliosis to prevent AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Astrócitos , Proteínas tau , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Feminino , Proteínas tau/metabolismo , Masculino , Idoso , Peptídeos beta-Amiloides/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Biomarcadores/sangue , Tomografia por Emissão de Pósitrons/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Proteína Glial Fibrilar Ácida/metabolismo , Proteína Glial Fibrilar Ácida/sangue , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/metabolismo , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Placa Amiloide/patologiaRESUMO
BACKGROUND: Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson's disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. METHODS: We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. RESULTS: QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. CONCLUSION: We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.
Assuntos
Doença de Parkinson , alfa-Sinucleína , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Humanos , Animais , Camundongos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Encéfalo/metabolismo , Encéfalo/patologia , Sensibilidade e Especificidade , Pele/metabolismo , Pele/patologia , Idoso de 80 Anos ou maisRESUMO
PURPOSE: [18F]-D3FSP is a new ß-amyloid (Aß) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear. METHODS: We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [18F]-D3FSP Aß PET imaging. We analyzed plasma Aß42/Aß40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated. RESULTS: Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau181 (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aß42/Aß40 (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings. CONCLUSION: This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aß plaques in the brain. [18F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [18F]-D3FSP PET images with other validated Aß PET tracers or postmortem results are crucial.
RESUMO
OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.
RESUMO
BACKGROUND: The aim of the present study was to develop a novel 64Cu-labeled cyclic peptide ([64Cu]Cu-FAP-NOX) that targets fibroblast activation protein (FAP) and may offer advantages in terms of image contrast, imaging time window, and low uptake in normal tissues. METHODS: The novel cyclic peptide featuring with a N-oxalyl modified tail was constructed and conjugated to NOTA for 64Cu labeling. Biochemical and cellular assays were performed with A549.hFAP cells. The performance of [64Cu]Cu-FAP-NOX was compared to that of two established tracers ([64Cu]Cu-FAPI-04 and [68Ga]Ga-FAP-2286) and three different NOTA-conjugates in HEK-293T.hFAP xenograft mice using micro-PET imaging. Ex vivo biodistribution studies were performed to confirm the FAP specificity and to validate the PET data. Furthermore, a first-in-human study of this novel tracer was conducted on one patient with lung cancer. RESULTS: Compared to [64Cu]Cu-FAPI-04, [64Cu]Cu-FAP-NOX demonstrated faster and higher rates of cellular uptake and internalization in A549.hFAP cells, but lower rates of cellular efflux. All six radiotracers were rapidly taken up by the tumor within the first 4 h post-injection. However, [64Cu]Cu-FAP-NOX had more intense tumor accumulation and slower washout from the target. The ratios of the tumor to normal tissue (including kidneys and muscles) increased significantly over time, with [64Cu]Cu-FAP-NOX reaching the highest ratio among all tracers. In the patient, [64Cu]Cu-FAP-NOX PET showed a comparable result to FDG PET in the primary malignant lesion while exhibiting higher uptake in pleural metastases, consistent with elevated FAP expression as confirmed by immunohistochemistry. CONCLUSION: [64Cu]Cu-FAP-NOX is a promising FAP-targeted tracer with a highly flexible imaging time window, as evidenced by preclinical evaluation encompassing biodistribution and micro-PET studies, along with a successful patient application. Furthermore, [64Cu]Cu-FAP-NOX showed enhanced image contrast and favorable pharmacokinetic properties for FAP PET imaging, warranting translation into large cohort studies.
RESUMO
BACKGROUND: This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC). METHODS: From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated. RESULTS: In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients. CONCLUSION: In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions. TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fluordesoxiglucose F18 , Neoplasias Pulmonares , Metástase Linfática , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pessoa de Meia-Idade , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Metástase Linfática/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 µm to 5 µm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.
RESUMO
OBJECTIVE: This inquiry probes the suicide resilience experiences in suicide attempts by self-poisoning among Chinese youth. The study's goal is to provide healthcare professionals with critical insights to develop effective interventions that enhance suicide prevention measures and diminish the likelihood of subsequent attempts. METHODS: Utilizing a qualitative phenomenological approach, we conducted semi-structured interviews with 12 youths (Mean age = 21.1 ± 2.8 years; n = 7 females) who survived suicide attempts by self-poisoning. Data analysis was performed using Colaizzi's seven-step method, a rigorous method entailing iterative reading for the extraction of key statements and the distillation of thematic essence. RESULTS: Four primary themes with ten sub-themes were extracted: (1) New understanding of life (cherish life, and meaning of life), (2) Self-Reconciliation (self-acceptance, self-understanding, and self-openness), (3) Personal empowerment (increased self-reliance, increased responsibility, and increased emotional regulation), and (4) Life redesigning (faith in the future, and plan for the future). CONCLUSIONS: The findings reveal a potential for psychological growth and beneficial transformation in youth following suicide attempts by self-poisoning. These insights advocate for the integration of positive psychology principles in therapeutic interventions for this demographic.
Assuntos
Pesquisa Qualitativa , Resiliência Psicológica , Tentativa de Suicídio , Humanos , Feminino , Masculino , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/etnologia , China , Adulto Jovem , Entrevistas como Assunto , Adolescente , Intoxicação/psicologia , População do Leste AsiáticoRESUMO
The neurotoxicity of fumonisin B1 (FB1), a commonly detected mycotoxin in crops and the environment, has attracted considerable attention in recent years. However, no effective method for eliminating FB1 completely exists due to the thermal stability and water solubility of this mycotoxin. Magnolol (MAG) is a neolignane with antioxidative and neuroprotective effects. It has been applied in neurotoxicity treatment. However, the application of MAG to attenuate FB1-induced toxicity has not been reported. This study explored the protective mechanism of MAG against FB1-induced damage in C6 cells through antioxidant and lipid metabolism modulation. Results showed that exposure to 15 µM FB1 caused oxidative stress by changing the levels of malondialdehyde, reactive oxygen species, total superoxide dismutase, catalase, and total glutathione. These changes were reversed by MAG addition, especially at the concentration of 80 µM. The protective effects of MAG were further confirmed by the reduction in the phosphorylation levels of proteins in the MAPK signaling pathway. Lipidomics analysis identified 263 lipids, which belong to 24 lipid classes. Among all of the identified lipids, triglycerides (TGs), diglycerides (DGs), phosphatidylcholines (PCs), wax monoesters (WEs), Cers, and phosphatidylethanolamines (PEs) were major categories. Moreover, nine categories of lipids showed the opposite change trend in the FB1 exposure and MAG 80 groups. A further investigation of the 34 co-occurring differential lipids with remarkable changes (P value < 0.05 and VIP value > 1) in the control, FB1 exposure, and MAG 80 groups was performed. Therein, nine lipids (PCs, LPCs, and SM) were screened out as potential biomarkers to reveal the cytoprotective effects of MAG. This work is the first to investigate the rescue mechanism of MAG in FB1-induced cytotoxicity. The obtained results may expand the application of MAG to alleviate the toxicity of mycotoxins.
Assuntos
Compostos de Bifenilo , Fumonisinas , Lignanas , Metabolismo dos Lipídeos , Estresse Oxidativo , Fumonisinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lignanas/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Ratos , Fármacos Neuroprotetores/farmacologia , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Lipidômica , Glutationa/metabolismoRESUMO
BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.
Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Feminino , Humanos , Teorema de Bayes , Algoritmos , Carcinoma Epitelial do Ovário , Aprendizado de MáquinaRESUMO
INTRODUCTION: The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer's disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort. METHODS: Following the standard protocols of the Alzheimer's Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), ß-amyloid (Aß) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aß42/Aß40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aß PET, and tau PET, respectively. Plasma biomarkers, Aß PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aß PET positivity were also determined in different diagnostic groups. RESULTS: The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aß PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported. DISCUSSION: The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aß PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aß PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China's older population.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Envelhecimento Saudável , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons , Biomarcadores , Proteínas tau , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/epidemiologiaRESUMO
PURPOSE: Acupuncture has been recommended as an effective therapy to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We conducted this secondary analysis to explore the factors that may influence the response of patients with CP/CPPS to acupuncture. METHODS: This secondary analysis was based on a randomized controlled trial demonstrating the efficacy of acupuncture among patients with CP/CPPS. Responder is defined as a patient with a decrease of ≥ 6 points in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score from baseline at the 32 week. 206 patients who received acupuncture treatment and completed 32-week follow-up were included in this secondary analysis. Descriptive statistics were used to describe the demographic and clinical characteristics of both responders and non-responders in acupuncture group. Logistic regression analysis with bootstrapping was made to identify potential factors that contributed to the effectiveness of acupuncture for treating CP/CPPS. Responders and non-responders were listed as dependent variables. RESULTS: In this study, 130 (63.11%) patients were assessed as responders. The results showed that men with non-sedentariness (OR 4.170 [95%CI 1.837 to 9.463; P = 0.001]), non-smoking habit (OR 2.824 [95%CI 1.453 to 5.487; P = 0.002]), without comorbidity (OR 8.788 [95%CI 1.912 to 40.295; P = 0.005]), and severe NIH-CPSI total score (OR 0.227 [95%CI 0.114 to 0.450; P < 0.0001]) benefited more from acupuncture intervention. CONCLUSION: CP/CPPS patients who are active, non-smokers, without comorbidity, and had severe symptoms may be more likely to respond to acupuncture.
Assuntos
Terapia por Acupuntura , Dor Crônica , Prostatite , Masculino , Humanos , Dor Crônica/terapia , Prostatite/complicações , Doença Crônica , Terapia por Acupuntura/métodos , Dor Pélvica/terapiaRESUMO
BACKGROUND: Necroptosis is an inflammatory cell death mode, and its association with multiple myeloma (MM) remains unclear. METHODS: This prospective study first analyzed the association between necroptosis-related signature as well as prognosis and chemotherapy sensitivity in MM using the necroptosis score. Consensus clustering was used to identify necroptosis-related molecular clusters. Least absolute shrinkage and selection operator analysis and multivariate Cox regression analysis were performed to establish the prognostic model of necroptosis-related genes (NRGs). RESULTS: A high necroptosis score was associated with poor prognosis and abundant immune infiltration. Two molecular clusters (clusters A and B) significantly differed in terms of prognosis and tumor microenvironment. Cluster B had a worse prognosis and higher tumor marker pathway activity than cluster A. The risk score model based on four NRGs can accurately predict the prognosis of patients with MM, which was validated in two validation cohorts. Receiver operating characteristic curve analysis showed that the area under the curves of the risk score in predicting the 1-, 3-, and 5-year survival rates were 0.710, 0.758, and 0.834, respectively. Further, the activity of pathways related to proliferation and genetic regulation in the high-risk group significantly increased. The drug prediction results showed that the low-risk score group was more sensitive to bortezomib, cytarabine, and doxorubicin than the high-risk score group. Meanwhile, the high-risk score group was more sensitive to lenalidomide and vinblastine than the low-risk score group. Finally, the upregulation of model genes CHMP1A, FAS, JAK3, and HSP90AA1 in clinical samples collected from patients with MM was validated via real-time polymerase chain reaction. CONCLUSION: A systematic analysis of NRGs can help identify potential necroptosis-related mechanisms and provide novel biomarkers for MM prognosis prediction, tumor microenvironment evaluation, and personalized treatment planning.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Necroptose , Estudos Prospectivos , Prognóstico , Bortezomib/farmacologia , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Potential risk factors for suicide differ by age group. Therefore, this study aims to investigate the characteristics of patients with suicide attempts according to age group and any the relevant risk factors. METHODS: This study retrospectively reviewed the medical records of attempted suicide patients who were admitted to the emergency departments (ED) of the First Affiliated Hospital of Wenzhou Medical University between January 1, 2017, and December 31, 2021. Demographic information and clinical characteristics were collected. The participants were divided into four age groups and the characteristics of each group were compared. RESULTS: A total of 834 participants were included in this study. Suicide attempts were more prevalent in females, and the gender difference decreased with age. Having religious belief and less educated suicide attempts were concentrated in the elderly groups. Adolescents suicide attempts were more likely to occur in the spring, autumn and during non-office hours. Mental disorders were the major motivation for suicide among adolescents, and interpersonal and social problems were more prevalent among youths. Psychiatric medication was the leading suicidal substances among adolescents, while pesticides and herbicides were more prevalent in adults. The history of psychiatric diagnosis was more common in adolescents, while the history of somatic disorder was more prevalent in the elderly. CONCLUSION: This study confirmed differences in the demographic and clinical characteristics of patients in different age groups. Therefore, it is necessary to construct individualized intervention strategies for each age group based on the characteristics of the patients in order to reduce suicide.
Assuntos
Transtornos Mentais , Tentativa de Suicídio , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Humanos , Adolescente , Estudos Retrospectivos , Transtornos Mentais/psicologia , Hospitalização , Fatores de Risco , China/epidemiologiaRESUMO
ABSTRACT: We compared 18 F-FAPI and 18 F-FDG PET/CT findings of metastatic perivacular epitheliod cell tumor in a 23-year-old woman. Apart from showing strong uptake of a left upper lung mass that showed moderate uptake on 18 F-FDG, 18 F-FAPI PET/CT additionally presented hypermetabolism in diffuse multifocal lesion throughout the body. This case suggests that 18 F-FAPI PET/CT might play a more beneficial role than 18 F-FDG PET/CT in identifying and assessing the extent of perivascular epithelioid cell tumors.
Assuntos
Metástase Neoplásica , Neoplasias de Células Epitelioides Perivasculares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias de Células Epitelioides Perivasculares/diagnóstico por imagem , Neoplasias de Células Epitelioides Perivasculares/patologia , Adulto Jovem , Fluordesoxiglucose F18RESUMO
PURPOSE: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. METHODS: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. RESULTS: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. CONCLUSION: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.
Assuntos
Fluordesoxiglucose F18 , Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Animais , Camundongos , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Masculino , Feminino , Linhagem Celular Tumoral , Células HEK293 , Distribuição Tecidual , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Idoso , Proteínas de Membrana , EndopeptidasesRESUMO
Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.
Assuntos
Proteína Morfogenética Óssea 2 , Modelos Animais de Doenças , Camundongos Knockout , Músculo Liso Vascular , Miócitos de Músculo Liso , Osteogênese , Insuficiência Renal Crônica , Transcrição Gênica , Calcificação Vascular , Animais , Humanos , Masculino , Camundongos , Doenças da Aorta/genética , Doenças da Aorta/prevenção & controle , Doenças da Aorta/patologia , Doenças da Aorta/metabolismo , Apoptose/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Regiões Promotoras Genéticas , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/prevenção & controle , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Calcificação Vascular/patologia , Calcificação Vascular/prevenção & controle , Calcificação Vascular/metabolismo , Calcificação Vascular/genética , Calcificação Vascular/etiologiaRESUMO
BACKGROUND: The prevailing mobile phone use brought the problem of addiction, which might cause negative consequences. Effortful control and mind wandering were associated with addictive behavior. The present study aimed to investigate the dimension-level relationships between effortful control, mind wandering, and mobile phone addiction. METHODS: A total of 1684 participants participated this study. The mobile phone addiction, effortful control, and mind wandering were measured through self-report scales, respectively. Dimension-level network of these psychological variables was estimated and bridge expected influence (BEI) values for each node was calculated. RESULTS: Dimensions of mobile phone addiction, effortful control, and mind wandering exhibited distinct and complex links to each other. The node "activation control" exhibited the highest negative BEI value (BEI = -0.32), whereas "spontaneous thinking" showed the highest positive BEI value (BEI = 0.20). CONCLUSIONS: Different dimensions of effortful control and mind wandering had varied yet significant connections with distinct dimensions of mobile phone addiction, facilitating understanding of the specific pathways underlying the three constructs. The identified dominant bridge nodes can provide potential targets for the intervention of mobile phone addiction.