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1.
Artigo em Inglês | MEDLINE | ID: mdl-39351778

RESUMO

CONTEXT: Turner syndrome (TS) is characterized by a partial or complete absence of the second X chromosome in female. Here, patients with Xp deletion involving SHOX haploinsufficiency caused by unbalanced X-autosome translocations were discussed and considered as TS variants. OBJECTIVE: This work aimed to expand the current knowledge of TS and unbalanced X-autosome translocations and to suggest the definition, clinical characteristics, diagnosis workflow and growth hormone (GH) treatment strategy of TS and its variants. METHODS: A 9.0-year-old patient of TS variant with tall target height (+2.03SD) but low height velocity (3.6cm/y) and height (-1.33SD) was evaluated as an example. Patients similar to the index patient were systematically searched in MEDLINE and EMBASE and summarized. A diagnosis workflow and scores for risk assessment of GH treatment (RiGHT scores) for TS variants were also proposed in this study. RESULTS: According to the diagnosis workflow, the girl's karyotype was confirmed as 46,X,der(X)t(X;7)(p11.3; p14.1), and was evaluated as low risk using RiGHT scores. After 2-year GH treatment, she had a significantly increased height (-0.94SD). Moreover, a total of 13 patients from 10 studies were summarized, characterized as short stature, growth retardation, craniofacial abnormalities, disorders of intellectual development, and psychomotor delays. Risk assessment of GH treatment using RiGHT scores were also applied in these 13 patients. CONCLUSION: The patients with Xp deletion caused by unbalanced X-autosome translocations should be considered as TS variants. The diagnosis workflow and RiGHT scores is a useful approach for clinicians in addressing complex cases of TS variants with GH treatment in clinical practice.

2.
Front Oncol ; 14: 1367140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351350

RESUMO

Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. The prognosis for patients diagnosed with early-stage EC remains favorable; however, for patients with recurrent or metastatic EC, the prognosis is poor and treatment options, until recently, are limited. Antibody drug conjugates (ADCs) represent innovative strategies in cancer treatment; however, there are less investigations regarding their efficacy in EC. This report describes an EC case with low human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) expression score (IHC 2+) that experienced recurrent metastasis in the abdominal and peritoneal following post-surgical chemotherapy and radiotherapy. Subsequently, the commencement of HER2-targeted ADC, disitamab vedotin (RC48; 2.5 mg/kg), administered intravenously every two weeks, was initiated. The tumor lesions shrunk markedly after three cycles of treatment and disappeared by the completion of ten cycles of therapy. The patient is still in remission at present. The current findings imply the potential efficacy of HER2-targeted ADCs for patients with HER2-low metastatic EC.

3.
Hellenic J Cardiol ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39384141

RESUMO

OBJECTIVES: This study investigated the association between the utilization of extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) and in-hospital mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock undergoing primary percutaneous coronary intervention (PCI). METHODS: Data encompassing 9635 cases of STEMI complicated by cardiogenic shock and treated with primary PCI using ECMO/IABP support were retrieved from the Chinese Cardiovascular Association database (2019-2021). We conducted an analysis to assess in-hospital survival disparities among percutaneous mechanical circulatory device recipients and explore the potential advantages of ECMO through multivariable logistic regression analysis within a propensity score-matched (1:2) cohort population. RESULTS: ECMO was administered to 2028 patients, while IABP was utilized in 7607 patients. Patients supported by ECMO showed a lower in-hospital mortality compared with those supported by IABP (7.2% vs. 15.1%, p<0.001). Within the propensity-matched (case : control=1:2) cohort, we noted a 34% reduced risk of in-hospital mortality among patients supported by ECMO compared to those supported by IABP (7.7% vs. 11.7%; odds ratio = 0.66; 95% CI, 0.53-0.80; p< 0.001) independent of age, sex, systolic blood pressure, obesity, smoke, hypertension, diabetes, dyslipidaemia, family history of coronary artery disease, coronary artery disease, stroke, atrial filiation, peripheral artery disease, chronic kidney disease, vascular lesion sites, 3A-grade hospital, and regional distributions in China. CONCLUSIONS: Among patients undergoing primary PCI for STEMI complicated by cardiogenic shock, ECMO was associated with better in-hospital survival than IABP.

4.
Cardiol Res Pract ; 2024: 1905996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39257436

RESUMO

Myocardial ischemia-reperfusion (I/R) injury is a significant area of focus in cardiovascular disease research. I/R injury can increase intracellular oxidative stress, leading to DNA damage. H2AX plays a crucial role in DNA repair. This study utilized mouse and cell models of myocardial I/R to investigate the impact of H2AX on cardiomyocytes during I/R. This study initially assessed the expression of H2AX in MI/R mice compared to a sham surgery group. Subsequently, cardiac function, infarct area, and mitochondrial damage were evaluated after inhibiting H2AX in MI/R mice and a negative control group. Furthermore, the study delved into the molecular mechanisms by analyzing the expression of H2AX, P53, p-JNK, SHP2, p-SHP2, p-RAS, parkin, Drp1, Cyt-C, Caspase-3, and Caspase-8 in cardiomyocytes following the addition of JNK or P53 agonists. The results from western blotting in vivo indicated significantly higher H2AX expression in the MI/R group compared to the sham group. Inhibiting H2AX improved cardiac function, reduced myocardial infarct area, and mitigated mitochondrial damage in the MI/R group. In vitro experiments demonstrated that inhibiting H2AX could attenuate mitochondrial damage and apoptosis in myocardial cells by modulating the P53 and JNK signaling pathways. These findings suggested that inhibiting H2AX may alleviate myocardial I/R injury through the regulation of the P53/JNK pathway, highlighting H2AX as a potential target for the treatment of myocardial ischemia/reperfusion injury.

5.
Mol Genet Genomic Med ; 12(9): e70009, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39286962

RESUMO

BACKGROUND: Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. METHODS: A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole-exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. RESULTS: A 13.3-year-old male patient with a height of 136.5 cm (-3.5 SDS) and a weight of 28.4 kg (-3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. CONCLUSION: This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.


Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Síndrome de Cornélia de Lange , Humanos , Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/patologia , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Adolescente , Fosfoproteínas/genética , Fenótipo , Mutação , Sequenciamento do Exoma
6.
Am J Med ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233017

RESUMO

PURPOSE: System delay is associated with mortality in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). However, the influence of patient delay has been relatively overlooked. We aimed to evaluate the influence of patient and system delays on STEMI patients undergoing primary PCI in China. METHODS: STEMI patients registered at the Nationwide Chinese Cardiovascular Association Database-Chest Pain Center from January 2017 to September 2021 were screened. The exposures were total ischemic time (TIT), system delay and patient delay. The primary outcome was in-hospital mortality. RESULTS: Among 458,260 patients from 2529 centers, median TIT, system delay and patient delay were 4.1, 1.5 and 2.1 hours, respectively. The adjusted odds ratio of in-hospital mortality increased by 2.2% (odds ratio [OR], 1.022, 95% confidence interval [CI], 1.017-1.027), 2.3% (1.023, 1.006-1.040) and 2.2% (1.022, 1.017-1.027) for every one-hour increase in TIT, system delay and patient delay, respectively. CONCLUSIONS: Patient delay demonstrated a comparable impact to system delay on in-hospital mortality among STEMI patients undergoing primary PCI. Widespread primary PCI-capable center, improved awareness about myocardial infarction and regional transfer system are essential to shorten patient delay.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39271770

RESUMO

BACKGROUND: The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). METHODS: Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. RESULTS: Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. CONCLUSION: Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

8.
Neuroendocrinology ; : 1-13, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39342927

RESUMO

INTRODUCTION: Male prolactinomas are uncommon and typically macroadenomas with difficult treatment and management. The purpose of this study was to summarize the treatment and management experiences of 254 male prolactinoma patients at a single center. METHODS: This was a 10-year retrospective study conducted at a single center. A total of 254 male prolactinoma patients were included. Clinical data for all subjects were collected using an electronic medical record system. RESULTS: A total of 254 male patients with prolactinoma were studied. Their median age at onset was 28.8 years, and median disease duration was 28.5 months. The median PRL levels were 582.0 ng/mL at diagnosis. Their median maximum tumor diameter was 23.0 mm, with macroadenoma accounting for the majority (76.7%). After treatment, the biochemical remission rate with monotherapy was 36.6%, but significantly increased to 60.6% with multidisciplinary treatment (p < 0.001). Knosp 0-2 patients had significantly higher rates of biochemical remission compared to Knosp 3-4 (all p < 0.05). In addition, the maximum diameter of adenoma (B = -0.110, p = 0.008) and cavernous sinus invasion (B = -1.741, p = 0.023) were negatively correlated with postoperative biochemical remission. The maximum diameter of the adenoma (B = - 0.131, p < 0.001) was a negative correlation factor, while treatment duration (B = 0.034, p = 0.002) was a positive correlation factor for biochemical response to medication. CONCLUSION: Male prolactinoma has a low biochemical remission rate when treated alone, but multitherapy can improve it even more. Surgery may also be considered for male prolactinoma with a micro, and noninvasive tumor after a thorough evaluation.

9.
Med Biol Eng Comput ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39098860

RESUMO

Heart sound signals are vital for the machine-assisted detection of congenital heart disease. However, the performance of diagnostic results is limited by noise during heart sound acquisition. A limitation of existing noise reduction schemes is that the pathological components of the signal are weak, which have the potential to be filtered out with the noise. In this research, a novel approach for classifying heart sounds based on median ensemble empirical mode decomposition (MEEMD), Hurst analysis, improved threshold denoising, and neural networks are presented. In decomposing the heart sound signal into several intrinsic mode functions (IMFs), mode mixing and mode splitting can be effectively suppressed by MEEMD. Hurst analysis is adopted for identifying the noisy content of IMFs. Then, the noise-dominated IMFs are denoised by an improved threshold function. Finally, the noise reduction signal is generated by reconstructing the processed components and the other components. A database of 5000 heart sounds from congenital heart disease and normal volunteers was constructed. The Mel spectral coefficients of the denoised signals were used as input vectors to the convolutional neural network for classification to verify the effectiveness of the preprocessing algorithm. An accuracy of 93.8%, a specificity of 93.1%, and a sensitivity of 94.6% were achieved for classifying the normal cases from abnormal one.

10.
Heliyon ; 10(15): e34866, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39145020

RESUMO

Numerous Payments for Ecosystem Services (PES) programs have been implemented simultaneously around the world but their outcomes in the literature are not consistent and their interactive effects remain understudied. The Natural Forest Conservation Program (NFCP) and Grain to Green Program (GTGP) are two largest PES programs in the world, and many studies have evaluated their effects on household income. However, the identified effects often varied across different studies and the factors explaining this variation are poorly understood. This study used linear regression and geographic detector analysis, based on questionnaire survey data from 14 giant panda natural reserves (NRs) in southwestern China, to evaluate the effects of the NFCP and GTGP on household income and the factors which moderate these effects. The results revealed that the effects of two PES programs on household income were spatially heterogeneous and enhanced by each other and livelihood activities, suggesting a synergistic interaction between policies and livelihood activities, particularly tourism. This study also found that livelihoods activities (e.g., labor migration and tourism), household capital (i.e., house area and farmland area) and demographic factors (i.e., number of labor and non-labor members), exhibit spatial heterogeneity in their effects on household income across NRs. These findings underscore the importance of considering local socioeconomic conditions and the interaction between policy and socio-economic conditions in PES program design to achieve desired outcomes, providing insights for policymakers and practitioners worldwide.

11.
Prostate ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162127

RESUMO

BACKGROUND: The current guidelines for treating metastatic castration-sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real-world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States. METHODS: This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics® Plus data set. The study focused on 10 common AEs (fatigue/asthenia, gastrointestinal [GI] AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in ≥10% of patients and ≥2% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow-up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT + nonsteroidal anti-androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT + docetaxel, and ADT + ARPIs (abiraterone, apalutamide, or enzalutamide). ADT-alone cohort was the reference group for all comparisons. RESULTS: A total of 4145 patients were included (ADT alone: 2318, ADT + NSAA: 632, ADT + docetaxel: 471, ADT + ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1-73.1) years; most common sites of metastasis were bone only (n = 1886, 45.5%) and node only (n = 1237, 29.8%); most used medications were pain medications (n = 2182, 52.6%) and corticosteroids (n = 1213, 29.3%). Median (IQR) duration of follow-up 10.2 (6.1-16.6) months in ADT alone, 6.7 (4.1-11.5) months in ADT + NSAA, 5.1 (4.3-5.9) months in ADT + docetaxel, and 11.0 (6.6-17.0) months in ADT + ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT + ARPI or ADT + NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT + docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia). During the follow-up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia, edema; p < 0.001 for all seven), three AEs in the ADT + ARPI group (hot flash, p = 0.05; anemia, p = 0.01; edema, p = 0.019), and one AE in the ADT + NSAA group (anemia, p = 0.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone. CONCLUSION: Results of this large, real-world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT + ARPIs were comparable with ADT + NSAA and not significantly different from ADT alone. ADT + docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real-world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better-informed decisions about disease management among patients with mCSPC.

12.
Menopause ; 31(9): 769-780, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39186452

RESUMO

OBJECTIVE: To assess treatment satisfaction, unmet treatment needs, and new vasomotor symptom (VMS) treatment expectations among women with moderate to severe VMS and physicians treating women with VMS. METHODS: This noninterventional, nonrandomized survey included qualitative interviews and quantitative surveys of women and physicians in the US. Participating women had moderate to severe VMS in the past year and received ≥1 hormone therapy (HT), non-HT, or over-the-counter (OTC) treatment for VMS in the past 3 months. Participating physicians were obstetrician-gynecologists (OB-GYNs) and primary care physicians (PCPs) who treated ≥15 women with VMS in the past 3 months. Two online survey questionnaires were developed using insights from literature, qualitative interviews, and clinical experts. Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) measured treatment satisfaction. Results were summarized descriptively. RESULTS: Questionnaires were completed by 401 women with VMS and 207 physicians treating VMS. Among women, mean total MS-TSQ score ranges were 62.8-67.3 for HT, 59.8-69.7 for non-HT, and 58.0-64.9 for OTC treatments. Among physicians, mean total MS-TSQ scores were considerably higher for HT than for non-HT and OTC treatments (HT: 73.4-75.6; non-HT: 55.6-62.1; OTC: 49.2-54.7). Women reported "lack of effectiveness" (41.2%), and physicians reported "long-term safety concerns" (56.5%) as main features that do not meet their current treatment expectations. The majority of women and physicians would consider trying a new non-HT treatment for VMS (75.8 and 75.9%, respectively). CONCLUSIONS: Treatment satisfaction and new treatment expectations were similar but with some differences between women and physicians; the need for additional treatments for VMS was identified.


Assuntos
Fogachos , Menopausa , Satisfação do Paciente , Humanos , Feminino , Pessoa de Meia-Idade , Menopausa/psicologia , Menopausa/fisiologia , Fogachos/tratamento farmacológico , Inquéritos e Questionários , Adulto , Idoso , Atitude do Pessoal de Saúde , Ginecologia , Médicos de Atenção Primária , Terapia de Reposição de Estrogênios , Estados Unidos , Sistema Vasomotor/fisiopatologia , Sistema Vasomotor/efeitos dos fármacos , Médicos/psicologia
13.
Micromachines (Basel) ; 15(7)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39064402

RESUMO

Bionic prosthetic hands hold the potential to replicate the functionality of human hands. The use of bionic limbs can assist amputees in performing everyday activities. This article systematically reviews the research progress on bionic prostheses, with a focus on control mechanisms, sensory feedback integration, and mechanical design innovations. It emphasizes the use of bioelectrical signals, such as electromyography (EMG), for prosthetic control and discusses the application of machine learning algorithms to enhance the accuracy of gesture recognition. Additionally, the paper explores advancements in sensory feedback technologies, including tactile, visual, and auditory modalities, which enhance user interaction by providing essential environmental feedback. The mechanical design of prosthetic hands is also examined, with particular attention to achieving a balance between dexterity, weight, and durability. Our contribution consists of compiling current research trends and identifying key areas for future development, including the enhancement of control system integration and improving the aesthetic and functional resemblance of prostheses to natural limbs. This work aims to inform and inspire ongoing research that seeks to refine the utility and accessibility of prosthetic hands for amputees, emphasizing user-centric innovations.

14.
Eur J Neurol ; 31(9): e16384, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38988097

RESUMO

BACKGROUND AND PURPOSE: Hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real-world outcomes of patients with ATTRv-PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch. METHODS: This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv-PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12-month patisiran treatment period. RESULTS: Among the 24 patients with ATTRv-PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy. CONCLUSIONS: Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv-PN.


Assuntos
Neuropatias Amiloides Familiares , Benzoxazóis , Polineuropatias , Humanos , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/complicações , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Benzoxazóis/uso terapêutico , Polineuropatias/tratamento farmacológico , Substituição de Medicamentos , Resultado do Tratamento , RNA Interferente Pequeno
15.
J Proteome Res ; 23(8): 3612-3625, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38949094

RESUMO

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide, causing significant health problems. Early diagnosis of the disease is quite inadequate. To screen urine biomarkers of DN and explore its potential mechanism, this study collected urine from 87 patients with type 2 diabetes mellitus (which will be classified into normal albuminuria, microalbuminuria, and macroalbuminuria groups) and 38 healthy subjects. Twelve individuals from each group were then randomly selected as the screening cohort for proteomics analysis and the rest as the validation cohort. The results showed that humoral immune response, complement activation, complement and coagulation cascades, renin-angiotensin system, and cell adhesion molecules were closely related to the progression of DN. Five overlapping proteins (KLK1, CSPG4, PLAU, SERPINA3, and ALB) were identified as potential biomarkers by machine learning methods. Among them, KLK1 and CSPG4 were positively correlated with the urinary albumin to creatinine ratio (UACR), and SERPINA3 was negatively correlated with the UACR, which were validated by enzyme-linked immunosorbent assay (ELISA). This study provides new insights into disease mechanisms and biomarkers for early diagnosis of DN.


Assuntos
Albuminúria , Biomarcadores , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Aprendizado de Máquina , Proteômica , Humanos , Nefropatias Diabéticas/urina , Nefropatias Diabéticas/diagnóstico , Biomarcadores/urina , Proteômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Albuminúria/urina , Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/urina , Diabetes Mellitus Tipo 2/complicações , Serpinas/urina , Calicreínas/urina , Idoso , Estudos de Casos e Controles , Creatinina/urina , Cininogênios
16.
Sci Total Environ ; 944: 173625, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38848927

RESUMO

Climate change can pose a significant threat to terrestrial ecosystems by disrupting the circulation of soil nitrogen. However, experimental analyses on the effect of climate change on soil nitrogen cycles and the implications for the conservation of key wildlife species (i.e., the giant panda, Ailuropoda melanoleuca) remain understudied. We investigated the effects of a 1.5 °C, 3 °C, and 4.5 °C temperature increase on nitrogen distribution in different soil layers of bamboo forest via an in-situ experiment and assessed the implications for the growth and survival of arrow bamboo (Bashania faberi), a critical food resource for giant pandas. Our results showed that warming treatments generally increased soil N content, while effects differed between surface soil and subsurface soil and at different warming treatments. Particularly an increase of 1.5 °C raised the subsurface soil NO3-N content, as well as the content of N in bamboo leaves. We found a significant positive correlation between the subsurface soil NO3-N content and the N content of arrow bamboo. An increase of 3-4.5 °C raised the content of total N and NO3-N in the surface soil and led to a reduction in the total aboveground biomass and survival rate of arrow bamboo. Limited warming (e.g., the increase of 0-1.5 °C) may promote the soil N cycle, raise the N-acetylglucosaminidase (NAG) enzyme activity, increase NO3-N in subsurface soil, increase the N content of bamboo, and boost the biomass of bamboo - all of which could be beneficial to giant panda survival. However, higher warming (e.g., an increase of 3-4.5 °C) resulted in mass death of bamboo and a large reduction in aboveground biomass. Our findings provide a cautiously optimistic scenario for bamboo forest ecosystems under low levels of warming over a short period of time, but risks from higher levels of warming may be serious, especially considering the unpredictability of global climatic change.


Assuntos
Mudança Climática , Ecossistema , Ciclo do Nitrogênio , Nitrogênio , Solo , Ursidae , Ursidae/fisiologia , Animais , Solo/química , Nitrogênio/análise , Poaceae , Sasa , China
17.
BMC Med Inform Decis Mak ; 24(1): 174, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902714

RESUMO

INTRODUCTION: The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet. MATERIAL AND METHODS: The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs. RESULTS: The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714-0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440-0.767), other models' AUCs displayed well. Thereinto, the RF algorithm's final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693-0.949). CONCLUSION: The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy.


Assuntos
Aprendizado de Máquina , Humanos , Feminino , Gravidez , Recém-Nascido , Adulto , China , Exposição à Radiação/efeitos adversos , Peso ao Nascer , Macrossomia Fetal
18.
Biomed Pharmacother ; 175: 116780, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781864

RESUMO

Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metabolômica , Pueraria , Ratos Sprague-Dawley , Animais , Pueraria/química , Masculino , Ratos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/sangue , Fígado/metabolismo , Fígado/efeitos dos fármacos , Administração Oral , Extratos Vegetais/farmacologia , Isoflavonas/farmacologia , Insulina/sangue , Insulina/metabolismo , Lipídeos/sangue
19.
Phytomedicine ; 129: 155667, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728918

RESUMO

BACKGROUND: It has been a current research hospots using fingerprinting technology for quality control of Chinese herbal medicines (CHMs), which provides a scientific basis for establishment of overall quality control in accordance with the characteristics of CHMs. The fingerprinting technology for CHMs is diverse, and the research field covers many disciplines, such as analytical chemistry, pharmacology, pharmaceutics, biochemistry, and molecular biology. PURPOSE: To effectively understand the key areas and future directions of research regarding the fingerprint and adulteration of CHMs. METHODS/RESULTS: this paper analyzed 879 articles in this field in the Web of Science Core Collection from 2000 to 2023 with CiteSpace and VOSviewer, and systematically assessed the research process, hotspots, topic distribution among disciplines, etc. The most prominent contributors of fingerprint and adulteration of CHMs research are mainly from China, India, the United States, England, and Brazil. The knowledge domains of fingerprint and adulteration of CHMs research focus mainly on the topics of molecular authentication, DNA barcoding, HPLC, near-infrared spectroscopy, manage data, chemometrics, and electrochemical fingerprinting. Most countries have recognized the pharmaceutical potential of natural products, and have paid more attention to the fingerprint and adulteration of CHMs in the past decade. Future the research tends to focus more on molecular identification and authentication, and electrochemical and chromatographic fingerprinting in controlling the adulteration of CHMs. CONCLUSION: This research provides a valuable reference for scholars in related fields to analyze existing research results, understand the development trend, and explore new research directions.


Assuntos
Contaminação de Medicamentos , Medicamentos de Ervas Chinesas , Controle de Qualidade , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Código de Barras de DNA Taxonômico
20.
Am J Physiol Endocrinol Metab ; 327(1): E134-E144, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747899

RESUMO

Perigonadal adipose tissue is a homogeneous white adipose tissue (WAT) in adult male mice without any brown adipose tissue (BAT). However, there are congenital differences in the gonads between male and female mice. Whether heterogeneity existed in perigonadal adipose tissues (ATs) in female mice remains unknown. This study reported a perigonadal brown-like AT located between abdominal lymph nodes and the uterine cervix in female mice, termed lymph node-cervical adipose tissue (LNCAT). Its counterpart, lymph node-prostatic adipose tissue (LNPAT), exhibited white phenotype in adult virgin male mice. When exposed to cold, LNCAT/LNPAT increased uncoupling protein 1 (UCP1) expression via activation of tyrosine hydroxylase (TH), in which abdominal lymph nodes were involved. Interestingly, the UCP1 expression in LNCAT/LNPAT varied under different reproductive stages. The UCP1 expression in LNCAT was upregulated at early pregnancy, declined at midlate pregnancy, and reverted in weaning dams. Mating behavior stimulated LNPAT browning in male mice. We found that androgen but not estrogen or progesterone inhibited UCP1 expression in LNCAT. Androgen administration reversed the castration-induced LNPAT browning. Our results identified a perigonadal brown-like AT in female mice and characterized its UCP1 expression patterns under various conditions.NEW & NOTEWORTHY A novel perigonadal brown-like AT (LNCAT) of female mice was identified. Abdominal lymph nodes were involved in cold-induced browning in this newly discovered adipose tissue. The UCP1 expression in LNCAT/LNPAT was also related to ages, sexes, and reproductive stages, in which androgen acted as an inhibitor role.


Assuntos
Tecido Adiposo Marrom , Colo do Útero , Linfonodos , Próstata , Proteína Desacopladora 1 , Animais , Masculino , Feminino , Camundongos , Linfonodos/metabolismo , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Tecido Adiposo Marrom/metabolismo , Colo do Útero/metabolismo , Próstata/metabolismo , Gravidez , Tecido Adiposo Branco/metabolismo , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Androgênios/farmacologia , Androgênios/metabolismo , Comportamento Sexual Animal/fisiologia
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