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Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0-8.3 months and progression-free survival (PFS, â¼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1-34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0-15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.
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Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.
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Human epidermal growth factor receptor 2 (HER2)+ gastric cancer (GC) is a distinct subtype of GC, accounting for 1020% of all cases of GC. Although the development of the antiHER2 monoclonal antibody trastuzumab has markedly improved response rates and prognosis of patients with HER2+ advanced GC (AGC), drug resistance remains a considerable challenge. Therefore, dynamic monitoring of HER2 expression levels can facilitate the identification of patients who may benefit from targeted therapy. Besides trastuzumab, DS8201 and RC48 have been applied in the treatment of HER2+ AGC, and several novel antiHER2 therapies are undergoing preclinical/clinical trials. At present, combination immunotherapy with antiHER2 agents is used as the firstline treatment of this disease subtype. New promising approaches such as chimeric antigen receptor Tcell immunotherapy and cancer vaccines are also being investigated for their potential to improve clinical outcomes. The current review provides new insights that will guide the future application of antiHER2 therapy by summarizing research progress on targeted therapy drugs for HER2+ AGC and combination treatments.
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Antineoplásicos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Trastuzumab/uso terapêutico , Receptor ErbB-2/metabolismo , Antineoplásicos/uso terapêutico , Prognóstico , ImunoterapiaRESUMO
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.
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Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Serina/metabolismo , Linhagem Celular TumoralRESUMO
Purpose: To assess the impacts of area-level socioeconomic and environmental measures on reduced visual acuity (VA). Methods: This ecological study used the nationally representative cross-sectional data from the Chinese National Survey on Students' Constitution and Health in 2014 (CNSSCH 2014), which included 261,833 participants aged 7 to 22 years randomly selected from 30 mainland provinces in China. Area-level socioeconomic measures assessed included gross domestic product (GDP), population density, density of hospital beds, and nighttime light data measured as the mean digital number (DN) of each region; environmental factors assessed included latitude, annual sunlight duration, and park green space density. The main outcome measure was the prevalence of reduced VA in each province of Mainland China. Results: GDP (coefficient: 0.221; P < 0.001), mean DN (coefficient: 0.461; P < 0.001), latitude (coefficient: 0.093; P < 0.001), and annual sunlight duration (coefficient: 0.112; P < 0.001) were positively associated with the prevalence of reduced VA, while population density (coefficient: -0.256; P < 0.001), park green space per 10,000 people (coefficient: -0.145; P < 0.001), and number of hospital beds per 10,000 people (coefficient: -0.146; P < 0.001) were negatively associated with reduced VA prevalence. Factor analysis indicated a marginally nonsignificant positive correlation between socioeconomic factors and the prevalence of reduced VA (coefficient: 0.034; P = 0.07). Conclusions: Increased GDP and mean DN, which reflect economic development, were associated with a higher prevalence of reduced VA, while larger park green space and number of hospital beds per 10,000 people seemed to play a protective role, which could be targeted to design preventive strategies for myopia.
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Fatores Socioeconômicos , Transtornos da Visão , Adolescente , Criança , Humanos , Povo Asiático , China , Estudos Transversais , Transtornos da Visão/epidemiologia , Acuidade Visual , Adulto JovemRESUMO
BACKGROUND: Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. METHODS: Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. RESULTS: CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. CONCLUSIONS: We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.
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OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade â ¡-â £) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage â ¢ AKI had a lower 1-year survival rate than those without AKI or with stage â AKI or stage â ¡ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage â ¢ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.
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Injúria Renal Aguda , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Criança , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Fatores de Risco , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Microangiopatias Trombóticas/complicaçõesRESUMO
Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.
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Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1-/- mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.
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Neoplasias da Mama/patologia , Proteína Tirosina Quinase CSK/genética , Fosfatidato Fosfatase/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Proteína Tirosina Quinase CSK/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Lipogênese/fisiologia , Masculino , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Camundongos Mutantes , Camundongos Transgênicos , Fosfatidato Fosfatase/genética , Fosforilação , Proto-Oncogene Mas , Tirosina/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.
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Broncoscopia , Silicones , Stents , Estenose Traqueal/cirurgia , Idoso , Gasometria , Dióxido de Carbono/sangue , Estudos de Casos e Controles , Dispneia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Qualidade de Vida , Estudos Retrospectivos , Estenose Traqueal/sangue , Estenose Traqueal/fisiopatologiaRESUMO
Objective: With the improvement of surgical operation, increasing incidence of secondary benign airway stenosis, as a complication of long-term tracheal intubation and tracheotomy, leads to significant increases in morbidity and mortality. Previous treatment of secondary benign airway stenosis was mainly based on surgical resection and reconstruction. There is an urgent need for new treatment methods except surgery, especially for those inoperable patients. Methods: This study retrospectively reviewed 20 patients who had treatments of secondary benign airway stenosis after tracheotomy with Montgomery T-tube. The clinical data including clinical features, efficacy, complications and prognosis were retrospectively evaluated. Results: Complete airway obstruction was 12/20, partial stenosis was 8/20, combined with airway granuloma and endoscopic granulation resection was 16/20, combined with scar stenosis and endoscopic balloon dilatation was 18/20. Plugging successfully was 19/20. Complications included mucous accumulation (20/20), secondary granulation tissue formation (13/20), subcutaneous soft tissue infection (1/20), and T-tube re-implantation (3/20). Conclusions: Montgomery T-tube implantation under rigid bronchoscopy is a safe, feasible and effective tracheal forming method with well tolerance for patients with benign airway stenosis. Secondary benign airway stenosis after tracheal intubation and tracheotomy is an indication of Montgomery T-tube implantation. Compared with the traditional tracheotomy, the advantage of Montgomery T-tube implantation is easy to make the patient phonate, significantly improving the quality of life of patients. T-tube implantation is safe, and the postoperative complications include mucous accumulation and formation of secondary T-tube granulation tissue.
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Broncoscopia , Constrição Patológica/fisiopatologia , Traqueia/cirurgia , Traqueostomia/efeitos adversos , Traqueostomia/métodos , Adulto , Idoso , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Qualidade de Vida , Estudos Retrospectivos , Traqueostomia/instrumentação , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D. METHODS: Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; nâ¯=â¯8), diabetes sham operation (DS; nâ¯=â¯8), and diabetic control (DC; nâ¯=â¯8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; nâ¯=â¯8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups. RESULTS: Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D. CONCLUSIONS: Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.
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Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Microbioma Gastrointestinal , Mediadores da Inflamação/sangue , Lipopolissacarídeos/sangue , Animais , Ceco/microbiologia , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Modelos Animais de Doenças , Derivação Gástrica/efeitos adversos , Hipoglicemiantes/sangue , Obesidade/cirurgia , Período Pós-Operatório , Ratos , Ratos Sprague-DawleyRESUMO
Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including small non-coding RNAs (small ncRNAs) and long non-coding RNAs (lncRNAs), are involved in tumor growth in lung cancer (LC). However, the specific role of DGCR5 in LC progression is not yet clear. In the present study, we found that DGCR5 was downregulated and miR-1180 was upregulated in the sera and tissues of LC patients and was correlated with poor prognosis. We also found that DGCR5 suppressed proliferation, migration and invasion of LC cell lines H520 and H1299. In addition, a luciferase reporter gene assay was used to investigate the regulatory relationship between DGCR5 and miR-1180. Furthermore, we suggested that DGCR5 inhibited the expression of AKT, GSK-3ß, and ß-catenin by targeting miR-1180. Based on these findings, DGCR5 might serve as a potential target for the development of effective anti-neoplastic therapies in lung cancer.
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A novel non-chromatographic speciation technique for ultra-trace arsenite [As(III)] and total arsenic (tAs) in Chinese herbal medicine (CHM) is developed and validated by electrolytic hydride generation (EHG) coupled with atomic fluorescence spectrometry (AFS). The studies show that As(III) can be converted efficiently to AsH3 on an L-cysteine modified carbon paste electrode (CMCPE), which has never been reported before. Significantly, other arsenic species such as arsenate [As(V)], monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) do not form any or only less volatile hydrides at low applied current mode (<1.0 A). The results also demonstrate that L-cysteine and graphite powder play different roles in the electrolytic generation of AsH3. Comparing with the traditional graphite electrode, CMCPE has better stability, sensitivity and interference tolerance. Under the optimal conditions, the limit of detection (LOD) of tAs and As(III) for this method are 0.087µgL-1 and 0.095µgL-1 respectively. The accuracy of the method is verified through the analysis of reference materials (CRM 08231 and SRM1568a), and the proposed method has been applied satisfactorily to the determination of As(III) and tAs in several CHM samples.
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Arsênio/análise , Arsenitos/análise , Carbono/química , Cisteína/química , Medicamentos de Ervas Chinesas/análise , Eletrodos , Espectrofotometria Atômica/métodos , Eletrólise , Limite de DetecçãoRESUMO
The objective was to assess the safety and outcome of cold snare technique used by flexible bronchoscopy in the treatment of airway benign neoplasms. The clinical data of 21 patients, who had airway benign neoplasm and were treated through the cold snare method in Sir Run Run Shaw Hospital, affiliated with the Zhejiang University, were retrospectively analyzed. The relief of the symptoms and occurrence of complications were observed and evaluated. All the tumors were benign and removed by cold snare. Postoperatively, we found that the treatment was completely effective in 12 patients, and there was a significant improvement in 7 patients and a moderate improvement in 2 patients, and no recurrence in follow-up visit. In conclusion, the cold snare technique is an economically feasible, safe, and effective method in the treatment of airway neoplasms.
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Broncoscopia/métodos , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Traqueia/cirurgia , Neoplasias da Traqueia/cirurgia , Prega Vocal/cirurgia , Adulto , Idoso , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traqueia/patologia , Resultado do Tratamento , Prega Vocal/patologiaRESUMO
This work describes a novel non-chromatographic approach for the accurate and selective determining As species by modified graphite electrode-based electrolytic hydride generation (EHG) for sample introduction coupled with atomic fluorescence spectrometry (AFS) detection. Two kinds of sulfydryl-containing modifiers, l-cysteine (Cys) and glutathione (GSH), are used to modify cathode. The EHG performance of As has been changed greatly at the modified cathode, which has never been reported. Arsenite [As(III)] on the GSH modified graphite electrode (GSH/GE)-based EHG can be selectively and quantitatively converted to AsH3 at applied current of 0.4A. As(III) and arsenate [As(V)] on the Cys modified graphite electrode (Cys/GE) EHG can be selectively and efficiently converted to arsine at applied current of 0.6A, whereas monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) do not form any or only less volatile hydrides under this condition. By changing the analytical conditions, we also have achieved the analysis of total As (tAs) and DMA. Under the optimal condition, the detection limits (3s) of As(III), iAs and tAs in aqueous solutions are 0.25µgL(-1), 0.22µgL(-1) and 0.10µgL(-1), respectively. The accuracy of the method is verified through the analysis of standard reference materials (SRM 1568a).
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Arsênio/análise , Técnicas de Química Analítica/métodos , Eletrodos , Grafite/química , Oryza/química , Espectrometria de Fluorescência , Água/química , Arsênio/química , Técnicas de Química Analítica/instrumentaçãoRESUMO
OBJECTIVES: Previous studies have shown duodenal-jejunal exclusion (DJE) results in the rapid resolution of type 2 diabetes; however, the underlying mechanism is unknown. This study aimed to measure the hepatic expression of insulin receptor substrate-2 (IRS-2) and glucose transporter-2 (GLUT-2) in type 2 diabetic rats post-DJE, and to investigate their roles in improved hepatic insulin resistance and glucose intolerance. METHODS: Type 2 diabetic Sprague-Dawley (SD) rats were randomly divided into DJE operation (DO) and control (DC) groups. Normal SD rats were also divided into DJE operation and control groups. Fasting plasma glucose and insulin concentrations were measured, and the quantitative insulin sensitivity check index (QUICKI) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were calculated. Eight weeks postoperation, the hepatic IRS-2 and GLUT-2 protein and mRNA levels were measured using western blotting and reverse transcription polymerase chain reaction, respectively. RESULTS: The fasting blood glucose in the DO group decreased from a preoperative level of 20.21 ± 2.14 mmol/L to 8.50 ± 2.19 mmol/L (P < 0.05) 8 wk post-DJE. A change in the QUICKI revealed a dramatic increase, and HOMA-IR showed a significant decrease in the DO group (P < 0.05). Additionally, the IRS-2 and GLUT-2 protein and mRNA levels at 8 wk postoperation were significantly increased in the DO group compared with the DC group. CONCLUSIONS: DJE led to upregulated hepatic IRS-2 and GLUT-2 expression in the hepatic insulin signaling pathway and improved insulin sensitivity in type 2 diabetic rats.
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Diabetes Mellitus Experimental/cirurgia , Duodeno/cirurgia , Derivação Gástrica/métodos , Resistência à Insulina , Jejuno/cirurgia , Fígado/metabolismo , Transdução de Sinais , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Transportador de Glucose Tipo 2/metabolismo , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Regulação para CimaRESUMO
OBJECTIVE: To investigate the expression of apolipoprotein A-I(ApoA-I) in eight histological types of renal neoplasms and to explore a new biomarker for differential diagnosis. METHODS: The immunochemistry was used to detect the expression of ApoA-I in 23 cases of renal tumors, including clear cell carcinoma,papillary cell carcinoma, chromophobe cell carcinoma, oncocytoma,multilocular cystic carcinoma, renal pelvis invasive urothelial carcinoma,metanephric adenoma and collecting ducts carcinoma. Five cases of cancer-adjacent normal tissues were obtained from another five renal tumor patients and were chosen as control group. RESULTS: In the 23 cases of renal tumors, ApoA-I was expressed in 21 cases (positive rate was 91.3%). There were only two in five cases of normal tissues which expressed this protein (positive rate was 40.0%). A significant differentiation was observed between the two groups(Z=-2.829,P=0.003). In renal clear cell carcinoma (RCC), ApoA-I expression level was correlated with the grade and stage of tumor tissues. ApoA-I was stained much more stronger in RCC II-III than in RCC I (Z=-2.070,P=0.038).In various histological types of renal cancer, ApoA-I was all expressed to some degrees. CONCLUSION: ApoA-I can be chosen as a tumor biomarker to differentiate various histological types of renal neoplasms.
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Apolipoproteína A-I/metabolismo , Neoplasias Renais/metabolismo , Adenoma Oxífilo/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células de Transição/metabolismo , Diagnóstico Diferencial , Humanos , Neoplasias Epiteliais e Glandulares/metabolismoRESUMO
Bronchioloalveolar carcinoma is a subtype of the lung adenocarcinoma. Early stage bronchioloalveolar carcinoma is usually asymptomatic, especially in the peripheral lung. Rarely, urticaria has been described occurring with lung cancer, usually small-cell lung cancer, but no case has been reported of the bronchioloalveolar carcinoma yet. We report here a unique and initial urticaria on a patient, lasting for 6 months, who finally was diagnosed as early stage bronchioloalveolar carcinoma (T1aN0M0). After treatment of surgery, the symptom of urticaria disappeared and did not recur. Therefore, we consider that utricaria is a possibly clinical manifestation in early stage bronchioloalveolar carcinoma.