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1.
Front Med (Lausanne) ; 11: 1370674, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988358

RESUMO

A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.

2.
Mol Cell ; 84(10): 1917-1931.e15, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38723633

RESUMO

Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Retículo Endoplasmático , Proteínas de Membrana , ATPases do Tipo-P , Dobramento de Proteína , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/química , Retículo Endoplasmático/metabolismo , Células HEK293 , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/química , Domínios Proteicos , Processamento de Proteína Pós-Traducional , ATPases Translocadoras de Prótons/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/química , ATPases do Tipo-P/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
3.
Sci Rep ; 14(1): 7594, 2024 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556542

RESUMO

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral/genética , Prognóstico , Ritmo Circadiano/genética , Neoplasias de Cabeça e Pescoço/genética
4.
Phytomedicine ; 123: 155190, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37972468

RESUMO

BACKGROUND: Acute lung injury (ALI) is distinguished by rapid and severe respiratory distress and prolonged hypoxemia. A traditional Chinese medicine (TCM), known as the Fuzhengjiedu formula (FZJDF), has been shown to have anti-inflammatory benefits in both clinical and experimental studies. The precise underlying processes, nevertheless, are yet unclear. PURPOSE: This study sought to enlighten the protective mechanism of FZJDF in ALI through the standpoint of the gut-lung crosstalk. METHODS: The impact of FZJDF on lipopolysaccharide (LPS)-induced ALI murine model were investigated, and the lung injury score, serum interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) expression were measured to confirm its anti-inflammatory effects. Additionally, gut microbiota analysis and serum and fecal samples metabolomics were performed using metagenomic sequencing and high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, respectively. RESULTS: FZJDF significantly induced histopathological changes caused by LPS-induced ALI as well as downregulated the serum concentration of IL-1ß and TNF-α. Furthermore, FZJDF had an effect in gut microbiota disturbances, and linear discriminant effect size analysis identified signal transduction, cell motility, and amino acid metabolism as the potential mechanisms of action in the FZJDF-treated group. Several metabolites in the LPS and FZJDF groups were distinguished by untargeted metabolomic analysis. Correlations were observed between the relative abundance of microbiota and metabolic products. Comprehensive network analysis revealed connections among lung damage, gut microbes, and metabolites. The expression of glycine, serine, glutamate, cysteine, and methionine in the lung and colon tissues was dysregulated in LPS-induced ALI, and FZJDF reversed these trends. CONCLUSION: This study revealed that FZJDF considerably protected against LPS-induced ALI in mice by regulating amino acid metabolism via the gut-microbiota-lung axis and offered thorough and in-depth knowledge of the multi-system linkages of systemic illnesses.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Pulmão/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aminoácidos/metabolismo , NF-kappa B/metabolismo
5.
São Paulo med. j ; 142(3): e2022264, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1515597

RESUMO

ABSTRACT BACKGROUND: The cardiopulmonary function of patients with obstructive sleep apnea (OSA) is significantly lower than that of patients with simple snoring and is significantly related to the severity of OSA. Currently, only a few studies have been conducted on cardiopulmonary exercise testing in overweight patients with OSA. OBJECTIVE: To analyze the correlation between cardiopulmonary exercise test (CPET) indices and the condition of overweight patients with OSA. DESIGN AND SETTING: Retrospective study in Guangdong Provincial Hospital of Chinese Medicine. METHODS: This study included 73 hospitalized overweight patients. The patients were divided into no, mild, moderate, and severe OSA groups. Differences in the CPET indices among the four groups were compared. The correlation between the CPET indices and conditions was analyzed. RESULTS: No, mild, moderate, and severe OSA groups had 18 men and 5 women, 11 men and 3 women, 12 men and 2 women, and 21 men and 1 woman, respectively (P > 0.05). No significant difference was observed in resting pulmonary function among the four groups (P > 0.05). In the CPET, the anaerobic threshold, maximum oxygen uptake, and oxygen pulse were significantly lower in the severe OSA group than those in the normal OSA group (P < 0.05). Moreover, CPET indices negatively correlated with the apnea-hypopnea index. CONCLUSION: Changes in CPET indices occurred earlier than changes in resting pulmonary function in patients with OSA. CPET might be a potential method for evaluating the severity of OSA combined with overweight status.

6.
Immunotherapy ; 15(10): 737-750, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37139963

RESUMO

Aim: To evaluate the efficacy and safety of first-line immunochemotherapy in the treatment of advanced esophageal squamous cell carcinoma (CRD42021287033). Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched to obtain randomized controlled trials, and the outcome indicators of the reports were compared and analyzed. Results: A total of 3163 patients from five reported randomized controlled trials were included in the meta-analysis. The results showed the comprehensive benefits of toripalimab combined with chemotherapy, in terms of overall survival (hazard ratio: 0.59; 95% CI: 0.43-0.81) and progression-free survival (hazard ratio: 0.58; 95% CI: 0.46-0.73). Conclusion: Toripalimab combined with chemotherapy may be a better choice for first-line immunochemotherapy, although this needs to be verified by clinical studies.


The treatment of cancer is an issue of importance to the general public. A number of drugs are available to treat cancer, including those that enhance the body's natural defense. Such drugs are also the first choice for cancer of the esophagus, which cannot be removed surgically. In this study, we analyzed five different first-choice drugs in different ways, including how long the patient survives and how long the patient lives without their disease getting worse. We found that toripalimab, which strengthens the body's natural defense, may be the best combination choice for use in combination with chemotherapy. Although further studies are needed to increase the reliability of the conclusions, we preliminarily consider that this drug is particularly promising.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Metanálise em Rede , Imunoterapia/métodos
7.
J Gastrointest Cancer ; 54(3): 693-702, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36243897

RESUMO

OBJECTIVE: Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. METHOD: In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. RESULTS: Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09-2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37-2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71-1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52-1.85), rates of R0 resection (RR 0.74; 95% CI 0.55-1.10), compliance (RR 0.52; 95% CI 0.12-2.26), and grade 3--4 toxicities (RR 0.78; 95% CI 0.57-1.06) were all similar between the two groups. CONCLUSION: In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3-4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Quimiorradioterapia , Reto/patologia , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Intervalo Livre de Doença , Resultado do Tratamento
8.
Mol Cell ; 82(18): 3453-3467.e14, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35961308

RESUMO

Membrane protein clients of endoplasmic reticulum (ER)-associated degradation must be retrotranslocated from the ER membrane by the AAA-ATPase p97 for proteasomal degradation. Before direct engagement with p97, client transmembrane domains (TMDs) that have partially or fully crossed the membrane must be constantly shielded to avoid non-native interactions. How client TMDs are seamlessly escorted from the membrane to p97 is unknown. Here, we identified ER-anchored TMUB1 as a TMD-specific escortase. TMUB1 interacts with the TMD of clients within the membrane and holds ∼10-14 residues of a hydrophobic sequence that is exposed out of membrane, using its transmembrane and cytosolic regions, respectively. The ubiquitin-like domain of TMUB1 recruits p97, which can pull client TMDs from bound TMUB1 into the cytosol. The disruption of TMUB1 escortase activity impairs retrotranslocation and stabilizes retrotranslocating intermediates of client proteins within the ER membrane. Thus, TMUB1 promotes TMD segregation by safeguarding the TMD movement from the membrane to p97.


Assuntos
Retículo Endoplasmático , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ubiquitina/metabolismo , Proteína com Valosina/genética , Proteína com Valosina/metabolismo
9.
Front Pharmacol ; 13: 900699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35668930

RESUMO

Background: Fc gamma receptor 3A (FCGR3A) encodes a receptor for the Fc portion of immunoglobulin G, which plays a significant role in the immune response. However, the role of FCGR3A in cancers remains unclear. This study aimed to visualize the prognostic landscape of FCGR3A in pan-cancer and investigate the relationship between FCGR3A expression and tumor microenvironment. Method: Based on the TCGA database, GTEx database, and GDSC database, we analyzed the expression of FCGR3A in pan-cancers and adjacent normal tissues and its relationship with prognosis, immune cells infiltration, immune-related genes, DNA mismatch repair (MMR) genes, DNA methylation, and drugs sensitivity. The gene alteration frequency of FCGR3A was acquired on the cBioportal website. Moreover, we constructed PPI networks, performed GO and KEGG analysis to illustrate the function, and signaling pathways of FCGR3A-related genes, and conducted gene set enrichment analysis (GSEA) of FCGR3A to further explore its potential biological functions. Result: The differential analysis results of the publicly available databases showed that FCGR3A was generally highly expressed in pan-cancer. Survival analysis revealed that FCGR3A predominated as a risk prognostic factor in most cancers. Additionally, the expression of FCGR3A was confirmed to be associated with several immune cells infiltration, multiple immune checkpoint genes, and DNA mismatch repair genes expression in generalized carcinoma. We also identified a negative correlation between FCGR3A and DNA methylation levels. Through GO/KEGG and GESA, we found that FCGR3A was involved in many pathologic and physiological processes, and was most closely related to tumor immune-related pathways. Drug sensitivity analysis showed that higher FCGR3A expression predicts a low IC50 value for the vast majority of drugs. Conclusions: FCGR3A may be an immune-oncogenic molecule that correlates with tumor immune infiltration levels and affects drug sensitivity, thus it can be served as a promising biomarker for cancer detection, prognosis, therapeutic design, and follow-up.

10.
Complement Ther Clin Pract ; 46: 101510, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34749040

RESUMO

BACKGROUND: Many middle-aged and older adults have more than one chronic health condition. It is therefore important to explore the effectiveness of interventions for multiple chronic conditions. Tai Chi is widely used in China and other countries, and many studies have examined the effect of Tai Chi on anxiety and depression. However, there are no systematic reviews of the effect of Tai Chi on anxiety and depression in various chronic conditions. This systematic review and meta-analysis aimed to evaluate the effects of Tai Chi on anxiety and depression symptoms in four chronic conditions: cancer, stroke, heart failure (HF), and chronic obstructive pulmonary disease (COPD). METHODS: We searched Chinese and English databases (Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Sinomed) from inception to October 2020. Review Manager version 5.2 and Stata version 12.0 were used to perform a systematic review. The quality of the included studies was evaluated using the Cochrane risk of bias tool. The study was registered with the PROSPERO database (number CRD42020209594). RESULTS: Of the 596 studies identified, we included 25 randomized controlled trials involving 1819 participants. Combined analysis of the four diseases showed statistically significant differences between the Tai Chi and control groups for anxiety symptoms (SMD -0.99, 95%CI: -1.5, -0.47; P < 0.01) and depressive symptoms (SMD 0.70, 95%CI: -1.01, -0.39; P < 0.01). Subgroup analyses showed statistically significant differences between the Tai Chi and control groups for depressive symptoms in stroke (SMD -0.43, 95%CI: -0.67, -0.18; P < 0.01) and HF (SMD -0.57, 95%CI: -0.8, -0.33; P < 0.01). However, no statistically significant differences were found for depressive symptoms in COPD or cancer. There were statistically significant differences between the Tai Chi and control groups for anxiety symptoms in stroke (SMD -0.60, 95%CI: -0.88, -0.32; P < 0.01) and cancer (SMD -0.69, 95%CI: -1.22, -0.17; P < 0.01), but not in COPD or HF. Subgroup, sensitivity, meta regression, and publication bias analyses showed high heterogeneity correlated with a single study and study quality. Sensitivity analysis showed that most meta-analysis results had good stability, but those for anxiety symptoms in COPD were unstable; therefore, careful interpretation is required. CONCLUSION: Tai Chi has a positive effect on anxiety and depression, especially for patients with cancer, stroke, and HF. However, given the weak evidence, this approach is not a substitute for psychiatric treatment.


Assuntos
Insuficiência Cardíaca , Neoplasias , Doença Pulmonar Obstrutiva Crônica , Acidente Vascular Cerebral , Tai Chi Chuan , Idoso , Ansiedade/etiologia , Ansiedade/terapia , Depressão/etiologia , Depressão/terapia , Insuficiência Cardíaca/terapia , Humanos , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia
11.
PLoS Genet ; 17(11): e1009879, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34735437

RESUMO

The utilization of heterosis is a successful strategy in increasing yield for many crops. However, it consumes tremendous manpower to test the combining ability of the parents in fields. Here, we applied the genomic-selection (GS) strategy and developed models that significantly increase the predictability of heterosis by introducing the concept of a regional parental genetic-similarity index (PGSI) and reducing dimension in the calculation matrix in a machine-learning approach. Overall, PGSI negatively affected grain yield and several other traits but positively influenced the thousand-seed weight of the hybrids. It was found that the C subgenome of rapeseed had a greater impact on heterosis than the A subgenome. We drew maps with overviews of quantitative-trait loci that were responsible for the heterosis (h-QTLs) of various agronomic traits. Identifications and annotations of genes underlying high impacting h-QTLs were provided. Using models that we elaborated, combining abilities between an Ogu-CMS-pool member and a potential restorer can be simulated in silico, sidestepping laborious work, such as testing crosses in fields. The achievements here provide a case of heterosis prediction in polyploid genomes with relatively large genome sizes.


Assuntos
Brassica napus/genética , Vigor Híbrido , Poliploidia , Variação Genética , Genoma de Planta , Modelos Genéticos , Locos de Características Quantitativas
12.
Ann Transl Med ; 9(20): 1546, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790752

RESUMO

BACKGROUND: Current prediction models of esophageal cancer (EC) are limited to predicting at a specific time point, and ignore changes in hazard ratios of predictive variables, known as time-varying effects. Our study aimed to investigate variables with time-varying effects in EC and to develop a prediction model that can update the 5-year predicted dynamic overall survival (DOS) probability during the follow-up period. METHODS: Firstly, the clinicopathological information and survival data of 4,541 patients with EC was obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2007 and 2011 for modeling. Secondly, the time-varying effect of variables was assessed and the dynamic prediction model was developed based on the proportional baselines landmark supermodel. RESULTS: Here, we found that age at diagnosis, sex, location of primary tumor, histological type, chemotherapy, surgery, and T stage showed significant time-varying effects on overall survival. Thirdly, the prediction model was validated by an internal SEER validation cohort and a Chinese patient cohort, respectively, and achieved promising results as follows: area under the curve (AUC) =0.733 (internal validation) and 0.864 (external validation). The heuristic shrinkage factor was 0.995. Finally, several clear cases were selected as examples for model application to map the patient's 5-year DOS curves and to respectively demonstrate the impact of different variables' time-varying effect on survival. CONCLUSIONS: Overall, our results suggest that the existence of time-varying effect highlights the importance of updating the predicted survival probability during the follow-up period. Moreover, this prediction model can be used to assist doctors in making more-individualized treatment decisions based on a dynamic assessment of patient prognosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33758502

RESUMO

OBJECTIVE: To investigate the prevalence and the risk factors of COPD in the Uyghur population in the Kashi region. METHODS: From August 2018 to March 2019, we recruited participants of Uyghur ethnicity and aged ≥40 years old from the Kashi region using a combined cluster sampling and random sampling method. We collected potential risk factors using questionnaire, and conduced lung function using a portable pulmonary function instrument. RESULTS: A total of 2963 participants were included in this analysis, of whom 1268 were males and 1695 were females. There were 504 participants with COPD, generating a prevalence of 17.01%. With the increase of age, the prevalence of COPD in different genders increased significantly. The results of different regions were χ2= 627.89, p < 0.01, indicating significant differences in the prevalence in different regions. Among them, based on the existing survey data, it is speculated that Shache county has the highest crude prevalence, but the sample size needs to be further expanded. The participants with high age, smoking, lower BMI, high waist circumference, systolic blood pressure, fried cooking and barbecue share more COPD than those who partake of fruits and vegetables in this study. CONCLUSION: The prevalence of COPD among the Uyghur population in the Kashi region is higher than the national rural average. Among them, high age, smoking, low BMI, high waist circumference, high systolic blood pressure, cooking methods that may be stir-fried and deep-fried barbecue are risk factors for COPD, and vegetable and fruit intake may be a protective factor for COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Inquéritos e Questionários
14.
Technol Cancer Res Treat ; 19: 1533033820957005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33034270

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) hold huge potential for both clinical applications and basic research into the management of cancer, but the relationship between CTC count and cervical cancer prognosis remains unclear. Therefore, research on this topic is urgently required. OBJECTIVE: This study investigated whether CTCs were detectable in patients with cervical cancer and whether CTC count was an indicator of prognosis. METHODS: We enrolled 107 patients with pathologically confirmed cervical cancer. CTCs were detected after radiotherapy or concurrent cisplatin-containing chemotherapy in all patients. We evaluated all medical records and imaging data as well as follow-up information to calculate progression-free survival (PFS). PFS was defined as the time until first diagnosis of tumor progression or death. We also analyzed the relationship between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. RESULTS: CTCs were identified in 86 of 107 patients (80%), and the CTC count ranged from 0 to 27 cells in 3.2 mL blood. The median progression-free survival (PFS) was 43.1 months. Patients in which CTCs were detected had a significantly shorter PFS than CTC-negative patients (P = 0.018). Multivariate analysis indicated that CTC count was an independent negative prognostic factor for survival. However, no correlation was observed between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. CONCLUSION: CTC count is an independent negative prognostic factor for cervical cancer.


Assuntos
Células Neoplásicas Circulantes/patologia , Intervalo Livre de Progressão , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Contagem de Células , Cisplatino/uso terapêutico , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Radioterapia/métodos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia
16.
J Biol Chem ; 294(52): 20084-20096, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31748412

RESUMO

The endoplasmic reticulum-associated degradation (ERAD) pathway mediates the endoplasmic reticulum-to-cytosol retrotranslocation of defective proteins through protein complexes called retrotranslocons. Defective proteins usually have complex conformations and topologies, and it is unclear how ERAD can thread these conformationally diverse protein substrates through the retrotranslocons. Here, we investigated the substrate conformation flexibility necessary for transport via retrotranslocons on the ERAD-L, ERAD-M, and HIV-encoded protein Vpu-hijacked ERAD branches. To this end, we appended various ERAD substrates with specific domains whose conformations were tunable in flexibility or tightness by binding to appropriate ligands. With this technique, we could define the capacity of specific retrotranslocons in disentangling very tight, less tight but well-folded, and unstructured conformations. The Hrd1 complex, the retrotranslocon on the ERAD-L branch, permitted the passage of substrates with a proteinase K-resistant tight conformation, whereas the E3 ligase gp78-mediated ERAD-M allowed passage only of nearly completely disordered but not well-folded substrates and thus may have the least unfoldase activity. Vpu-mediated ERAD, containing a potential retrotranslocon, could unfold well-folded substrates for successful retrotranslocation. However, substrate retrotranslocation in Vpu-mediated ERAD was blocked by enhanced conformational tightness of the substrate. On the basis of these findings, we propose a mechanism underlying polypeptide movement through the endoplasmic reticulum membrane. We anticipate that our biochemical system paves the way for identifying the factors necessary for the retrotranslocation of membrane proteins.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático/efeitos dos fármacos , Células HEK293 , Proteínas do Vírus da Imunodeficiência Humana/genética , Proteínas do Vírus da Imunodeficiência Humana/metabolismo , Humanos , Leupeptinas/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Desdobramento de Proteína , Receptores do Fator Autócrino de Motilidade/genética , Receptores do Fator Autócrino de Motilidade/metabolismo , Especificidade por Substrato , Trimetrexato/farmacologia , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/metabolismo
18.
Curr Med Sci ; 38(5): 880-887, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341524

RESUMO

The efficacy and applied value of endoscopic hematoma evacuation vs. external ventricular drainage (EVD) in the treatment of severe ventricular hemorrhage (IVH) were explored and compared. From Jan. 2015 to Dec. 2016, the clinical data of 42 cases of IVH were retrospectively analyzed, including 18 patients undergoing endoscopic hematoma evacuation (group A), and 24 patients receiving EVD (group B). The hematoma clearance rate was calculated by 3D Slicer software, and complications and outcomes were compared between the two groups. There were no significant differences in age, sex and Graeb score between groups A and B (P>0.05). The hematoma clearance rate was 70.81%±27.64% in group A and 48.72%±36.58% in group B with a statistically significant difference (P<0.05). The operative time in groups A and B was 72.45±25.26 min and 28.54±15.27 min, respectively (P<0.05). The Glasgow Coma Scale (GCS) score increased from 9.28±2.72 at baseline to 11.83±2.91 at 1 week postoperatively in group A, and from 8.25±2.62 at baseline to 10.79±4.12 at 1 week postoperatively in group B (P<0.05). The length of hospital stay was 12.67±5.97 days in group A and 17.33±8.91 days in group B with a statistically significant difference (P<0.05). The GOS scores at 6 months after surgery were 3.83±1.12 in group A, and 2.75±1.23 in group B (P<0.05). These results suggested that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate, fewer complications and better outcomes in the treatment of severe IVH, indicating it is a safe, effective and promising approach for severe IVH.


Assuntos
Hemorragia Cerebral Intraventricular/cirurgia , Ventrículos Cerebrais/cirurgia , Drenagem/métodos , Endoscopia/métodos , Idoso , Hemorragia Cerebral Intraventricular/fisiopatologia , Ventrículos Cerebrais/fisiopatologia , Drenagem/efeitos adversos , Endoscopia/efeitos adversos , Feminino , Fibrinolíticos/administração & dosagem , Escala de Coma de Glasgow , Hematoma/fisiopatologia , Hematoma/cirurgia , Humanos , Injeções Intraventriculares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Int Med Res ; 46(7): 2976-2982, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29756504

RESUMO

Although the infectious diseases tuberculosis (TB) and cryptococcosis both cause formation of single or multiple nodules in immunodeficient hosts, cases of co-infection of these diseases are rarely seen. We report a patient who was co-infected with TB and cryptococcosis. A male patient with no clinical evidence of immunodeficiency presented with a 3-week history of abdominal distension accompanied by oedema of recurring lower extremities. The patient was diagnosed with tuberculous peritonitis and tuberculous pleurisy by an abdominal puncture biopsy. Several months after being treated for TB, the patient was diagnosed with Cryptococcus infection and received antifungal treatment. Computed tomographic and magnetic resonance imaging findings suggested that treatment was effective. This case illustrates the challenges encountered during assessment of neoplasms associated with TB and cryptococcosis. Differential diagnosis requires an abdominal puncture biopsy. Diagnosis of Cryptococcus infection also requires a positive cryptococcal culture and positive India ink staining analysis. Notably, our patient also showed no obvious symptoms of cryptococcosis after receiving anti-TB treatment. Accordingly, in this report, we discuss the possible pathogenic mechanisms that underlie the coincidence of both types of inflammatory lesions. We emphasize the need for a greater awareness of atypical presentations of TB accompanied by Cryptococcus infection.


Assuntos
Coinfecção/diagnóstico , Criptococose/diagnóstico , Pneumopatias/diagnóstico , Peritonite Tuberculosa/diagnóstico , Pleurisia/diagnóstico , Tuberculose Pleural/diagnóstico , Antifúngicos/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção/tratamento farmacológico , Criptococose/tratamento farmacológico , Humanos , Pneumopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Peritonite Tuberculosa/tratamento farmacológico , Pleurisia/tratamento farmacológico , Tuberculose Pleural/tratamento farmacológico
20.
Chem Commun (Camb) ; 54(7): 778-781, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29308791

RESUMO

An ultra-high fluorescence enhancement for two dyes on photonic crystal films was achieved to construct a two-color immuno-dot blot assay. This assay was demonstrated to simultaneously detect chemokine receptor co-expressed in cancer cells and reveal their co-operative and subtle changes after binding with respective ligands and drugs.


Assuntos
Cor , Fluorescência , Corantes Fluorescentes/química , Hibridização in Situ Fluorescente , Receptores de Quimiocinas/análise , Células HeLa , Humanos , Receptores de Quimiocinas/biossíntese
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