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Background: Four-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) is a relatively new type of MRI acquisition technique that provides a unique and comprehensive set of information within a single acquisition, including hemodynamic and anatomical information. This study was designed to noninvasively evaluate the correlation between the presence and severity of spontaneous splenorenal shunt (SRS) or gastrorenal shunt (GRS) and 4D flow MRI-derived parameters. Methods: This retrospective case-control study enrolled 70 patients who were diagnosed with hepatocirrhosis portal hypertension and admitted to the Second Affiliated Hospital of Chongqing Medical University. Patients were divided into three groups according to the diameter of the SRS and GRS. 4D flow MRI-derived parameters, including the turbulent kinetic energy, total volume (TV), flow velocity, blood flow volume (BFV), maximum flow (MF), wall shear stress, and relative pressure, were obtained for eight cut planes: proximal to the splenomesenteric confluence and liver hilum of the portal vein (PV1/PV2); the left/right branch of the bifurcation of the PV (LPV/RPV), at the mesosplenic confluence of the splenic vein (SV1), at the splenic hilum of the SV (SV2); at the proximal to the splenomesenteric confluence of the superior mesenteric vein (SMV1), and 5 cm from the splenomesenteric confluence of the SMV (SMV2). Comparisons among the three groups were based on one-way analysis of variance (ANOVA). Logistic regression was used to identify the risk factors for small SRS/GRS (S-SRS/GRS) and for large SRS/GRS (L-SRS/GRS). Receiver operating characteristic curves were used to evaluate the diagnostic performance of the independent risk factors for SRS and GRS. The associations between the clinical data and the 4D flow MRI-derived parameters of GRS and SRS were assessed via Spearman correlation coefficient analysis. Results: The presence of SRS or GRS was correlated with TVLPV (r=-0.302; P=0.035), TVPV1 (r=-0.385; P=0.001), TVPV2 (r=-0.301; P=0.013), BFVPV1 (r=-0.360; P=0.010), BFVSMV2 (r=0.371; P=0.008), MFPV1 (r=-0.341; P=0.004), and MFPV2 (r=-0.291; P=0.017). Meanwhile, the severity of the SRS or GRS was correlated with alanine aminotransferase level (r=-0.535; P<0.001), BFVLPV (r=-0.560; P=0.008), aspartate aminotransferase level (r=-0.321; P=0.038), and model for end-stage liver disease score (r=0.323; P=0.039). TVPV1, TVPV2, BFVPV1, BFVPV2, and MFSMV2 were found to be independent risk factors for L-SRS/GRS, with intermediate diagnostic efficacy, with the area under the curve (AUC)TV PV1=0.706 [95% confidence interval (CI): 0.519-0.853; sensitivity, 61.54%; specificity, 80.77%; P=0.018], AUCBFV PV1 =0.694 (95% CI: 0.507-0.844; sensitivity, 95.00%; specificity, 63.16%; P=0.035), AUCTV PV2 =0.729 (95% CI: 0.544-0.870; sensitivity, 77.78%; specificity, 66.67%; P=0.016), AUCBFV PV2 =0.718 (95% CI: 0.531-0.862; sensitivity, 60.00%; specificity, 82.35%; P=0.017), and AUCMF SMV2 =0.788 (95% CI: 0.608-0.912; sensitivity, 44.00%; specificity, 84.46%; P=0.005), respectively. As the TV of PV1 and PV2 and the BFV of PV1 and PV2 decreased, the risk of L-SRS/GRS increased. As the MF of SMV2 increased, the risk of the presence of L-SRS/GRS increased. Conclusions: 4D flow MRI-derived parameters correlated with the presence and severity of SRS or GRS. Meanwhile, the independent risk factors for the presence of L-SRS/GRS were the TV of LPV, PV1, and PV2; the BFV of PV1 and SMV2; and the MF of PV1 and PV2.
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As a glycoprotein hormone, human chorionic gonadotropin (hCG) is an established marker for pregnancy test. On the basis of the target-mediated silver deposition (TSD), in this work, we report the development of an amplification-free electrochemical biosensor for the highly sensitive detection of hCG. The detection of hCG involves the use of the affinity peptide-modified electrode for hCG capture (the CGGSSPPLRINRHILTR peptide containing the hCG-binding domain of the PPLRINRHILTR sequence is used as the affinity peptide), the oxidation of the diol sites of the glycan chains on hCG hormones into aldehyde groups by NaIO4, and the deposition of silver nanoparticles (AgNPs) for the solid-state voltammetric stripping analysis. Due to the deposition of multiple AgNPs while the solid-state Ag/AgCl voltammetric process has a high signal-to-noise ratio, the TSD-based electrochemical biosensor can be applied to the highly sensitive detection of hCG without the need for signal amplification. Under optimal conditions, the stripping current increased linearly with an increasing hCG concentration over the range from 1.0 to 25 mIU/mL, with a detection limit of 0.45 mIU/mL. Owing to the high specificity of the hCG-binding peptide PPLRINRHILTR, this electrochemical hCG biosensor exhibits high selectivity. The results of the quantitative assay of hCG in urine samples at the concentrations of 25, 10, and 1.0 mIU/mL are desirable, indicating the good anti-interference capability. As the TSD-based electrochemical biosensor allows the amplification-free detection of low-abundance hCG, it is easy to use and cost-effective, showing great promise in point-of-care assay of hCG for pregnancy test.
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Glycoproteins have become the most often screened tumor markers in the in vitro diagnostics. Although a large number of electrochemical methods have been proposed to sensitively detect glycoproteins, most of them involve the aid of laborious signal amplification. Herein, we report the use of glycan-evocated metallization (GlyMetal) for the amplification-free electrochemical detection of glycoproteins at low concentration levels. Briefly, the glycoproteins of interest are captured by an aptamer recognition layer, and then the glycans of targets are oxidized by NaIO4 to convert the 1,2-diol sites into aldehyde groups for the silver deposition-based metallization, followed by the electrochemical stripping assay of the deposited metallic silver for glycoprotein quantification via the established solid-state Ag/AgCl voltammetric process. As GlyMetal can enable the deposition of a large amount of metallic silver and a high signal-to-background ratio can be obtained for the solid-state Ag/AgCl voltammetric stripping assay, the developed GlyMetal-based electrochemical method is applicable to the amplification-free detection of glycoproteins. As a proof of concept, a detection limit of 1.65 pg/mL has been achieved for carcinoembryonic antigen (CEA) detection. In addition to the high selectivity, desirable results have been obtained with respect to the use of the method for CEA detection in serum samples. In consideration of the desirable simplicity, short assay time, and cost-effectiveness of the amplification-free approach, the GlyMetal-based electrochemical method shows great promise in the point-of-care detection of glycoproteins.
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BACKGROUND: Identifying patients with peritoneal metastasis (PMs) of colorectal cancer (CRC) who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery. Inflammatory and nutritional indicators play essential roles in cancer development and metastasis. AIM: To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM. METHODS: We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018. Patients' demographics, overall survival (OS), and preoperative inflammatory and nutritional markers were evaluated. The Kaplan-Meier method and log-rank test were used to estimate differences. RESULTS: Of the 133 patients, 94 (70.6%) had normal hemoglobin (Hb) and 54 (40.6%) had a high neutrophil-to-lymphocyte ratio (NLR). The median OS (mOS) was significantly lower for patients with high NLR (7.9 months) than for those with low NLR (25.4 months; P = 0.002). Similarly, patients with normal Hb had a longer mOS (18.5 months) than those with low Hb (6.3 months; P < 0.001). Multivariate analysis identified age, carbohydrate antigen 199 levels, NLR, Hb, and peritoneal cancer index as independent predictors of OS. Based on these findings, a nomogram was constructed, which demonstrated a good capacity for prediction, with a C-index of 0.715 (95% confidence interval: 0.684-0.740). Furthermore, the 1- and 2-year survival calibration plots showed good agreement between predicted and actual OS rates. The areas under the curve for the 1- and 2-year survival predictions of the nomogram were 0.6238 and 0.6234, respectively. CONCLUSION: High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM. The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM, indicating its potential as a valuable prognostic tool for this patient population.
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The biological activities of natural products (NPs) provided precious resources for the development of new drugs. Numerous studies have shown that statins exhibit cytotoxic potential, which is now an extensive focus of investigation. Herein, a remarkably efficient method for modification of statins using hexadehydro-Diels-Alder (HDDA) arynes has been described. Notably, lactone, as the biologically active group of statins, was removed during the reaction and a novel modified lignan skeleton was generated via the Alder-ene process. Unexpectedly, these statin-derived novel chemical scaffolds exhibited moderate inhibition effects on the proliferation of cancer cells as determined by CCK-8 assays, and the IC50 values were in the micromolar range.
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Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Hidroximetilglutaril-CoA Redutases , Lignanas , Lignanas/farmacologia , Lignanas/química , Lignanas/síntese química , Humanos , Proliferação de Células/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Desenho de Fármacos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a DrogaRESUMO
Rice (Oryza sativa L.) production frequently faces threats from biotic and abiotic stressors, with rice ragged stunt virus (RRSV) as a substantial biotic factor. The relationship between inorganic phosphorus (Pi) content and susceptibility to RRSV is crucial yet poorly understood. This study investigates how phosphorus metabolism influences rice resistance to RRSV, focusing on genetic manipulations that modulate this relationship. The RRSV infection increased phosphate (Pi) content in the aerial parts of rice plants by enhancing Pi uptake and transport. Furthermore, the upregulation of microRNA399d (miR399d) and the suppression of its target gene OsPHOSPHATE2 (OsPHO2) enhanced Pi accumulation, increasing rice susceptibility to RRSV infection. Additionally, elevated Pi levels, which are associated with altered ROS dynamics, reduced ROS activity and potentially dampened the plant's innate immune response to viral infection. The miR399d-PHO2 module was identified as pivotal in mediating phosphate uptake and influencing susceptibility to RRSV through modulations in the phosphorus and ROS pathways. This study shed light on the regulatory mechanisms of phosphorus nutrition in rice, revealing a critical interaction between phosphorus metabolism, ROS dynamics, and viral defense. The findings suggest potential strategies for manipulating Pi levels to enhance plant resistance against viruses, opening avenues for agricultural improvements and disease management in rice.
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An unprecedented fused hexacyclic indolizine derivative generated by a single-pot reaction has been developed. This model overcomes the use of catalysts, inefficient atom economy, low yields, and limitations of lengthy steps. Density functional theory calculations reveal the reaction mechanism in which the oxygen molecule plays a crucial role in trapping the penultimate zwitterionic or biradical intermediate to generate the observed products.
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Ferrocenyl conjugated oxazepine/quinoline derivatives were presented through the reaction of hexadehydro-Diels-Alder (HDDA) generated arynes with ferrocenyl oxazolines under mild conditions via ring-expanding or rearrangement processes. Water molecule participated in this unexpected rearrangement process to produce quinoline skeletons, and DFT calculations supported a ring-expanding and intramolecular hydrogen migration process for the formation of oxazepine derivatives. Two variants of this chemistry, expanded the reactivity between ferrocenyl conjugated substances and arynes, further providing an innovative approach for the synthesis of ferrocene derivatives.
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Introduction: Epidural analgesia has been studied for its potential advantages after surgery in a number of randomized clinical trials, with most finding improvements in pain and secondary endpoints like the incidence of postoperative complications. Aim: To assess the relationship between use of epidural analgesia and adverse cardiac outcomes expressed by myocardial infarction (MI). Material and methods: Fifty-three studies were recruited to quantify the influence of different surgical-related analgesic methods on clinical parameters (mortality and adverse events). The results of these trials were analysed using a random effects model, which was then used to calculate the mean difference (MD) with 95 per cent confidence intervals (CIs). Results: Epidural analgesia resulted in preferred cardiac outcomes compared with traditional analgesia. These findings were supported by significantly lower MI events for the epidural analgesia group as follows: p = 0.005, p = 0,007, and p = 0.03 for the total number of included studies, studies with high risk of bias, and studies with low risk of bias, respectively. Studies with intermediate risk showed a non-significant difference between both groups (p = 0.7). Conclusions: Epidural analgesia has a significant protective cardiac effect through the reduction of postoperative MI events among surgery subjects.
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The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.
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Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Flavonas , Rim , Panax notoginseng , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica , Transdução de Sinais , Animais , Camundongos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Panax notoginseng/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Rim/patologia , Rim/efeitos dos fármacos , Astrágalo/química , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta PressãoRESUMO
A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.
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Sepsis-induced acute kidney injury (S-AKI) is one of the most serious life-threatening complications of sepsis. The pathogenesis of S-AKI is complex and there is no effective specific treatment. Therefore, it is crucial to choose suitable preclinical models that are highly similar to human S-AKI to study the pathogenesis and drug treatment. In this review, we summarized recent advances in the development models of S-AKI, providing reference for the reasonable selection of experimental models as basic research and drug development of S-AKI.
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Injúria Renal Aguda , Modelos Animais de Doenças , Sepse , Injúria Renal Aguda/etiologia , Sepse/complicações , Animais , HumanosRESUMO
Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Masculino , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Pessoa de Meia-Idade , Feminino , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Idoso , Pulmão/microbiologia , Pulmão/virologia , Adulto , MetagenômicaRESUMO
A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.
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OBJECTIVE: To examine the manifestation of cognitive control deficit of children with different levels of hyperactivity, an "at risk" dimension for ADHD. METHOD: A group of children with high hyperactivity (N = 40) and another group of children with low levels of hyperactivity (N = 38) performed a modified stop-signal anticipation task, a revised Go/NoGo task, and the AX-continuous performance test (AX-CPT). RESULTS: Children with higher levels of hyperactivity displayed: (1) significantly prolonged stop signal reaction time (SSRT) in the modified stop-signal anticipation task; (2) no notable differences in commission errors in the revised Go/NoGo task; (3) increased reaction time (RT) in stop-signal task and Go/NoGo task with increased probabilities of stop or NoGo signal; and (4) positive proactive behavioral index scores in AX-CPT. CONCLUSION: The results suggested that children with heightened hyperactivity exhibited impaired reactive control, especially for responses already underway, but preserved proactive control. Further studies concerning these children are warranted.
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Transtorno do Deficit de Atenção com Hiperatividade , Testes Neuropsicológicos , Tempo de Reação , Humanos , Criança , Masculino , Feminino , Tempo de Reação/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Desempenho Psicomotor/fisiologia , Função Executiva/fisiologia , Inibição Reativa , Inibição ProativaRESUMO
Antibody pharmaceuticals have become the most popular immunotherapeutic drugs and are often administered with low serum drug dosages. Hence, the development of a highly sensitive method for the quantitative assay of antibody levels is of great importance to individualized therapy. On the basis of the dual signal amplification by the glycan-initiated site-directed electrochemical grafting of polymer chains (glyGPC), we report herein a novel strategy for the amplified electrochemical detection of antibody pharmaceuticals. The target of interest was affinity captured by a DNA aptamer ligand, and then the glycans of antibody pharmaceuticals were decorated with the alkyl halide initiators (AHIs) via boronate cross-linking, followed by the electrochemical grafting of the ferrocenyl polymer chains from the glycans of antibody pharmaceuticals through the electrochemically controlled atom transfer radical polymerization (eATRP). As the glycans can be decorated with multiple AHIs and the grafted polymer chains are composed of tens to hundreds of electroactive tags, the glyGPC-based strategy permits the dually amplified electrochemical detection of antibody pharmaceuticals. In the presence of trastuzumab (Herceptin) as the target, the glyGPC-based strategy achieved a detection limit of 71.5 pg/mL. Moreover, the developed method is highly selective, and the results of the quantitative assay of trastuzumab levels in human serum are satisfactory. Owing to its uncomplicated operation and cost-effectiveness, the glyGPC-based strategy shows great promise in the amplified electrochemical detection of antibody pharmaceuticals.
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Aptâmeros de Nucleotídeos , Técnicas Eletroquímicas , Trastuzumab , Técnicas Eletroquímicas/métodos , Humanos , Trastuzumab/química , Trastuzumab/sangue , Aptâmeros de Nucleotídeos/química , Limite de Detecção , Polissacarídeos/química , Técnicas Biossensoriais/métodos , Polímeros/químicaRESUMO
Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], P = 0.0004; HR = 1.79, 95% CI [1.40-2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], P < 0.0001; HR = 1.66, 95% CI [1.07-2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619.
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Cetuximab , Quimiorradioterapia , Cisplatino , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Cetuximab/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/administração & dosagem , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/tratamento farmacológico , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estadiamento de Neoplasias , Papillomaviridae , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Intervalo Livre de Progressão , Papillomavirus HumanoRESUMO
Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.
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Neoplasias da Mama , Organoides , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Organoides/patologia , Organoides/efeitos dos fármacos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Metástase Neoplásica , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piperazinas/uso terapêutico , Piperazinas/administração & dosagem , Resultado do TratamentoRESUMO
Lithium-sulfur batteries (Li-S) have possessed gratifying development in the past decade due to their high theoretical energy density. However, the severe polysulfide shuttling provokes undesirable self-discharge effect, leading to low energy efficiency in Li-S batteries. Herein, an interlayer composed of oxygen-rich carbon nanosheets (OCN) derived from bagasse is elaborated to suppress the shuttle effect and reduce the resultant self-discharge effect. The OCN interlayer is able to physically block the shuttling behavior of polysulfides and its oxygen-rich functional groups can strongly interact with polysulfides via O-S bonds to chemically immobilize mobile polysulfides. The self-discharge test for seven days further shows that the self-discahrge rate is diminished by impressive 93 %. As a result, Li-S batteries with the OCN interlayer achieve an ultrahigh discharge specific capacity of 710â mAh g-1 at a high mass loading of 7.18â mg. The work provides a facile method for designing functional interlayers and opens a new avenue for realizing Li-S batteries with high energy efficiency.
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Purpose: This study aimed to examine the impact of a history of SARS-CoV-2 infection on the hesitancy of college students to receive additional COVID-19 vaccine booster doses. Methods: A population-based self-administered online survey was conducted in July 2024 in Taizhou, China. A total of 792 respondents were included in this study. Logistic regression was conducted to identify factors associated with college students' hesitation to receive booster doses of the COVID-19 vaccine. Results: Of 792 respondents, 32.2 % hesitated to receive additional doses of the COVID-19 vaccine booster. Furthermore, 23.5 % of the respondents reported an increase in hesitancy to receiving additional COVID-19 vaccine booster doses compared to before they were infected with SARS-CoV-2. In the regression analyses, college students who had a secondary infection were more hesitant to receive additional COVID-19 vaccine booster doses (OR = 0.481, 95 % CI: (0.299-0.774), P = 0.003). Moreover, students with secondary infections who were male (OR = 0.417, 95 % CI: 0.221-0.784, P = 0.007), with lower than a bachelor's degree (OR = 0.471, 95 % CI: 0.272-0.815, P = 0.007), in non-medical majors (OR = 0.460, 95 % CI: 0.248-0.856, P = 0.014), and sophomores or below (OR = 0.483, 95 % CI: 0.286-0.817, P = 0.007) were more hesitant to receive additional COVID-19 vaccine booster doses. Conclusion: A history of SARS-CoV-2 infection affects college students' hesitation to receive additional COVID-19 vaccine booster doses, which was higher in those who experienced secondary infections.