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1.
Quant Imaging Med Surg ; 14(8): 5932-5945, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39144053

RESUMO

Background: The incidence rate of thyroid nodules has reached 65%, but only 5-15% of these modules are malignant. Therefore, accurately determining the benign and malignant nature of thyroid nodules can prevent unnecessary treatment. We aimed to develop a deep-learning (DL) radiomics model based on ultrasound (US), explore its diagnostic efficacy for benign and malignant thyroid nodules, and verify whether it improved the diagnostic level of physicians. Methods: We retrospectively included 1,076 thyroid nodules from 817 patients at three institutions. The radiomics and DL features of the US images were extracted and used to construct radiomics signature (Rad_sig) and deep-learning signature (DL_sig). A Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. Clinical US semantic signature (C_US_sig) was constructed based on clinical information and US semantic features. Next, a combined model was constructed based on the above three signatures in the form of a nomogram. The model was constructed using a development set (institution 1: 719 nodules), and the model was evaluated using two external validation sets (institution 2: 74 nodules, and institution 3: 283 nodules). The performance of the model was assessed using decision curve analysis (DCA) and calibration curves. Furthermore, the C_US_sigs of junior physicians, senior physicians, and expers were constructed. The DL radiomics model was used to assist the physicians with different levels of experience in the interpretation of thyroid nodules. Results: In the development and validation sets, the combined model showed the highest performance, with areas under the curve (AUCs) of 0.947, 0.917, and 0.929, respectively. The DCA results showed that the comprehensive nomogram had the best clinical utility. The calibration curves indicated good calibration for all models. The AUCs for distinguishing between benign and malignant thyroid nodules by junior physicians, senior physicians, and experts were 0.714-0.752, 0.740-0.824, and 0.891-0.908, respectively; however, with the assistance of DL radiomics, the AUCs reached 0.858-0.923, 0.888-0.944, and 0.912-0.919, respectively. Conclusions: The nomogram based on DL radiomics had high diagnostic efficacy for thyroid nodules, and DL radiomics could assist physicians with different levels of experience to improve their diagnostic level.

2.
Sci Total Environ ; 951: 175538, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151625

RESUMO

As the primary contributor to carbon emissions, how cities enhance their carbon emission performance and mitigate emissions is crucial for achieving low-carbon urban environments in China. However, existing research often overlooks the spatial interconnectedness of carbon emission performance, neglecting reciprocal influences among cities. This study examines the network structure of carbon emission performance among Guangdong's cities from 1997 to 2019, using a super-efficient SBM model and social network analysis, and measures spatial impacts of network factors with the spatial Durbin model. Findings reveal that: (1) The overall network of carbon emission performance is relatively loose with minimal changes in connectivity and efficiency but shows significant local clustering. (2) Shenzhen, Guangzhou, and Zhuhai have high centrality, dominating carbon emission performance resources and acting as key transmission nodes, while most other regions have low centrality, indicating network polarization and potential vulnerabilities. (3) Enhancing a region's centrality, economic development, industrial structure, openness, and attraction of talent and technology can boost local carbon emission performance, but may also lead to the displacement of emissions to neighboring areas and outflow of low-carbon and innovative elements, negatively affecting surrounding regions through spatial spillover effects. This research advances regional carbon emission reduction strategies by highlighting the interplay between spatial networks and carbon emission performance, fostering synergies in reduction efforts.

3.
Mil Med Res ; 11(1): 58, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39164787

RESUMO

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/história , Procedimentos Cirúrgicos Robóticos/tendências , Neoplasias da Próstata/cirurgia , Inteligência Artificial/tendências
4.
Sci Signal ; 17(848): eadl1030, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106320

RESUMO

Hexanucleotide repeat expansion in the C9ORF72 gene is the most frequent inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansion results in multiple dipeptide repeat proteins, among which arginine-rich poly-GR proteins are highly toxic to neurons and decrease the rate of protein synthesis. We investigated whether the effect on protein synthesis contributes to neuronal dysfunction and degeneration. We found that the expression of poly-GR proteins inhibited global translation by perturbing translation elongation. In iPSC-differentiated neurons, the translation of transcripts with relatively slow elongation rates was further slowed, and stalled, by poly-GR. Elongation stalling increased ribosome collisions and induced a ribotoxic stress response (RSR) mediated by ZAKα that increased the phosphorylation of the kinase p38 and promoted cell death. Knockdown of ZAKα or pharmacological inhibition of p38 ameliorated poly-GR-induced toxicity and improved the survival of iPSC-derived neurons from patients with C9ORF72-ALS/FTD. Our findings suggest that targeting the RSR may be neuroprotective in patients with ALS/FTD caused by repeat expansion in C9ORF72.


Assuntos
Esclerose Lateral Amiotrófica , Proteína C9orf72 , Expansão das Repetições de DNA , Demência Frontotemporal , Células-Tronco Pluripotentes Induzidas , Neurônios , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Humanos , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Neurônios/metabolismo , Neurônios/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Expansão das Repetições de DNA/genética , Elongação Traducional da Cadeia Peptídica , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Estresse Fisiológico/genética , Ribossomos/metabolismo , Ribossomos/genética
5.
Br J Radiol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102827

RESUMO

OBJECTIVE: To determine whether adding elastography strain ratio (SR) and a deep learning based computer-aided diagnosis (CAD) system to breast ultrasound (US) can help reclassify Breast Imaging Reporting and Data System (BI-RADS) 3 & 4a-c categories and avoid unnecessary biopsies. METHODS: This prospective, multicenter study included 1049 masses (691 benign, 358 malignant) with assigned BI-RADS 3 & 4a-c between 2020 and 2022. CAD results was dichotomized possibly malignant vs. benign. All patients underwent SR and CAD examinations and histopathological findings were the standard of reference. Reduction of unnecessary biopsies (biopsies in benign lesions) and missed malignancies after reclassified (new BI-RADS 3) with SR and CAD were the outcome measures. RESULTS: Following the routine conventional breast US assessment, 48.6% (336 of 691 masses) underwent unnecessary biopsies. After reclassifying BI-RADS 4a masses (SR cut-off < 2.90, CAD dichotomized possibly benign), 25.62% (177 of 691 masses) underwent an unnecessary biopsies corresponding to a 50.14% (177 vs. 355) reduction of unnecessary biopsies. After reclassification, only 1.72% (9 of 523 masses) malignancies were missed in the new BI-RADS 3 group. CONCLUSION: Adding SR and CAD to clinical practice may show an optimal performance in reclassifying BI-RADS 4a to 3 categories, and 50.14% masses would be benefit by keeping the rate of undetected malignancies with an acceptable value of 1.72%. ADVANCES IN KNOWLEDGE: Leveraging the potential of SR in conjunction with CAD holds immense promise in substantially reducing the biopsy frequency associated with BI-RADS 3 and 4A lesions, thereby conferring substantial advantages upon patients encompassed within this cohort.

6.
BMC Ophthalmol ; 24(1): 323, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103779

RESUMO

INTRODUCTION: Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. OBJECTIVE: To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. METHODS: A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. RESULTS: ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. CONCLUSIONS: We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.


Assuntos
Idade Gestacional , Redes Neurais de Computação , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Estudos Retrospectivos , Recém-Nascido , Feminino , Masculino , Fatores de Risco , Valor Preditivo dos Testes , Curva ROC , Triagem Neonatal/métodos , Algoritmos
7.
J Colloid Interface Sci ; 677(Pt B): 30-39, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39133996

RESUMO

The universal programmed construction of patterned periodic self-assembled nanostructures is a technical challenge in DNA origami nanotechnology but has numerous potential applications in biotechnology and biomedicine. In order to circumvent the dilemma that traditional DNA origami requires a long unusual single-stranded virus DNA as the scaffold and hundreds or even thousands of short strands as staples, we report a method for constructing periodically-self-folded rolling circle amplification products (RPs). The repeating unit is designed to have 3 intra-unit duplexes (inDP1,2,3) and 2 between-unit duplexes (buDP1,2). Based on the complementary pairing of bases, RPs each can self-fold into a periodic grid-patterned ribbon (GR) without the help of any auxiliary oligonucleotide staple. Moreover, by using only an oligonucleotide bridge strand, the GRs are connected together into the larger and denser planar nano-fence-shaped product (FP), which substantially reduces the number of DNA components compared with DNA origami and eliminates the obstacles in the practical application of DNA nanostructures. More interestingly, the FP-based DNA framework can be easily functionalized to offer spatial addressability for the precise positioning of nanoparticles and guest proteins with high spatial resolution, providing a new avenue for the future application of DNA assembled framework nanostructures in biology, material science, nanomedicine and computer science that often requires the ordered organization of functional moieties with nanometer-level and even molecular-level precision.

8.
Neuron ; 112(15): 2459-2461, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39116837

RESUMO

Aggregation of RNA binding proteins and dysregulation of RNA metabolism drives pathogenesis of multiple neurodegenerative diseases. In this issue of Neuron, Belur et al.1 identified pathological NONO/SFPQ inclusions and aberrant A-to-I-edited RNAs accumulated in nucleus, leading to dysregulation of gene expression and neurodegeneration in synucleinopathy-associated diseases.


Assuntos
Edição de RNA , Sinucleinopatias , Humanos , Sinucleinopatias/metabolismo , Sinucleinopatias/genética , Sinucleinopatias/patologia , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Corpos de Inclusão/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Animais , RNA/genética , RNA/metabolismo
9.
Ther Adv Med Oncol ; 16: 17588359241264730, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091606

RESUMO

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124922, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39096671

RESUMO

It has been well established that Hydrogen sulfide (H2S) is involved in various pathophysiological processes. Therefore, accurate monitoring H2S levels in vitro or vivo is of great significance in biological systems. Herein, we firstly developed a thiomaleimide-based compound MAL-1 bearing aggregation-induced emission characteristic for selective response toward H2S due to its nucleophilicity. The proposed sensor presented prominent sensitivity and selectivity with low detection limit of 75 nM and pseudo-first-order reaction rate constant of 9.65 × 10-2 s-1, as well as low cytotoxicity which works well in recognizing H2S in real samples and visualizing H2S in living cells. Thus, it could be concluded that the novel thiomaleimide-based probe would be a promising tool for assessing intracellular H2S levels.

11.
Cell Rep Med ; : 101678, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39096912

RESUMO

Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, ß-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or ß-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, ß-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that ß-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.

12.
Lung Cancer ; 195: 107901, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39089004

RESUMO

BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

13.
Front Pharmacol ; 15: 1351871, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015370

RESUMO

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

14.
Quant Imaging Med Surg ; 14(7): 4815-4824, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022240

RESUMO

Background: Intraplaque neovascularization (IPN) is a biomarker for vulnerable atherosclerotic plaques and can be effectively visualized via contrast-enhanced ultrasound (CEUS). Plaque elasticity is influenced by elements such as lipid core and fibrosis and can be quantitatively assessed on shear wave elastography (SWE). Studies combining the use of CEUS and SWE for the assessment of stroke risk are currently lacking. Our study thus aimed to determine the predictive value of IPN combined with plaque elasticity among patients with asymptomatic carotid plaque. Methods: Consecutive patients with mild carotid stenosis who underwent CEUS and SWE were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque, while plaque elasticity was measured in terms of mean shear wave velocity (SWV). All patients were followed up for 6 months to monitor the development of ischemic stroke. The predictive values of IPN and SWV, individually and in combination, were assessed. Results: A total of 121 patients were included, of whom 95 (78.5%) were male. The mean age was 63.1±10.7 years. Both grade 2 IPN [hazard ratio (HR) =2.37, 95% confidence interval (CI): 1.58-9.65; P=0.039] and SWV (HR =0.43, 95% CI: 0.20-0.95; P=0.038) were independently associated with future ischemic stroke events. The combined model demonstrated a significantly better predictive performance (HR =3.243, 95% CI: 1.87-6.17; P=0.027). Conclusions: The combination of IPN and SWV demonstrated significantly better predictive value for the risk of stroke. Our combined model thereby has the potential to guide the clinical stratification and management of patients with asymptomatic mild carotid stenosis.

15.
Nat Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992123

RESUMO

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

16.
Clin Transl Oncol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083141

RESUMO

Prognostic assessment is of great significance for individualized treatment and care of cancer patients. Although the TNM staging system is widely used as the primary prognostic classifier for solid tumors in clinical practice, the complexity of tumor occurrence and development requires more personalized probability prediction models than an ordered staging system. By integrating clinical, pathological, and molecular factors into digital models through LASSO and Cox regression, a nomogram could provide more accurate personalized survival estimates, helping clinicians and patients develop more appropriate treatment and care plans. Esophageal adenocarcinoma (EAC) is a common pathological subtype of esophageal cancer with poor prognosis. Here, we screened and comprehensively reviewed the studies on EAC nomograms for prognostic prediction, focusing on performance evaluation and potential prognostic factors affecting survival. By analyzing the strengths and limitations of the existing nomograms, this study aims to provide assistance in constructing high-quality prognostic models for EAC patients.

17.
Bioact Mater ; 36: 565-579, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39072287

RESUMO

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

18.
Front Med (Lausanne) ; 11: 1380640, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828231

RESUMO

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

19.
Zhongguo Gu Shang ; 37(6): 5835-90, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910381

RESUMO

OBJECTIVE: To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures. METHODS: Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively, and divided into open reduction and internal fixation group (posterior medial approach hollow anchor system fixation) and arthroscopic fixation group (Endobutton with loop plate fixation under arthroscopy). There were 20 patients in open reduction and internal fixation group, including 16 males and 4 females, aged from 26 to 74 years old with an average of (42.9±18.8) years old;13 patients on the left side and 7 patients on the right side;12 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were gradeⅡand 6 patients were grade Ⅲ in back drawer test. There were 18 patients in arthroscopic fixation group, including 11 males and 7 females;aged from 24 to 70 years old with an average of (53.5±13.4) years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;11 patients were gradeⅡand 7 patients were grade Ⅲ in back drawer test. Operation time, blood loss, and quality of immediate reduction were compared between two groups. Knee range of motion, knee back drawer test, and International Knee Documentation Committee(IKDC) grading, KT2000 stability evaluation and Lysholm function score of knee joint were compared at 6 months after operation. RESULTS: All patients were followed up for 8 to 16 months with an average of (12.3±1.9) months. There were no complications such as incision infection, fracture malunion or non-union, and internal fixation loosening occurred. The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation. Operation time and blood loss in open reduction and internal fixation group were (56.4±7.1) min and (63.2±10.2) ml, while (89.9±7.4) min and (27.7±8.7) ml in arthroscopic fixation group, respectively, and had significant difference between two groups (P<0.05). There were no differences in immediate reduction quality (χ2=0.257, P=0.612), knee joint range of motion at 6 months after opertaion (t=0.492, P=0.626), knee joint rear drawer test ( χ2=0.320, P=0.572), IKDC classification of knee joint (χ2=0.127, P=0.938), KT2000 stability evaluation (χ2=0.070, P=0.791), and knee Lysholm function score (t=0.092, P=0.282) between two groups. CONCLUSION: Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixation for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results, and arthroscopic surgery has less bleeding, but also has a longer learning curve and longer operation time than traditional incision surgery. The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.


Assuntos
Artroscopia , Placas Ósseas , Fixação Interna de Fraturas , Ligamento Cruzado Posterior , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artroscopia/métodos , Adulto , Idoso , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Estudos Retrospectivos , Fratura Avulsão/cirurgia , Pinos Ortopédicos
20.
Pregnancy Hypertens ; 37: 101135, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38936015

RESUMO

OBJECTIVES: To improve timely treatment and follow-up of birthing individuals with severe hypertension. STUDY DESIGN: A quality improvement (QI) initiative was implemented at an academic tertiary care center in the United States of America for individuals with obstetric hypertensive emergencies. Statistical process control charts were utilized to track process measures and interventions tested through plan-do-study-act cycles. Measures were disaggregated by race and ethnicity to identify and improve disparities. MAIN OUTCOME MEASURES: Treatment of hypertensive events within 60 min, receipt of blood pressure (BP) device at discharge and completed postpartum follow-up BP check within 7 days of discharge. RESULTS: All process measures showed statistically significant improvements. The primary process measure, timely treatment of hypertensive emergencies, improved from 29 % to 76 %. Receipt of BP device improved from 37 % to 91 % and follow-up BP checks from 58 % to 81 %. No racial or ethnic disparities were noted at baseline or after interventions. Readmission rates within 6 weeks of delivery increased from 2.3 % to 6.1 % for the cohort with no severe morbidity or mortality events after discharge. Strategies associated with improvement included project launch with establishment of the "why," telehealth, simulation, a video display of quality metrics on the birthing unit, promoting BP cuff access, and automated orders. CONCLUSIONS: This comprehensive QI initiative provides novel improvement strategies for the management of individuals with severe hypertensive disorders of pregnancy for the timely treatment of severe BP, attainment of home BP devices, and follow-up after discharge. Quality improvement methodology is practical and essential for achieving guideline-concordant care.

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