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The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.
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Bactérias , Bacteriófagos , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Bactérias/virologia , Bactérias/genética , Bactérias/imunologia , Bacteriófagos/genética , Bacteriófagos/imunologia , Chryseobacterium/genética , Chryseobacterium/imunologia , Chryseobacterium/virologia , Proteína 9 Associada à CRISPR/química , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Sistemas CRISPR-Cas/imunologia , Clivagem do DNA , Loci Gênicos/genética , Modelos Moleculares , Domínios ProteicosRESUMO
In populations in China, colorectal cancer (CRC) screening can be mainly accessed through organized screening, opportunistic screening, and physical examination. This screening intervention is found to be effective but the exact coverage rate is difficult to measure. Based on data from published articles, official websites, and available program reports, the screening coverage rate and related indicators were quantified. A rapid review was then conducted to estimate the overall and the breakdown coverage rates of the sub-type screening services, by leveraging the numbers of articles and the by-type median sample sizes. Up to 2020, two central government-funded and four provincial/municipal-level organized CRC screening programs have been initiated and included in this analysis. For populations aged 40-74, the estimated coverage rate of organized programs in China was 2.7% in 2020, and the 2-year cumulative coverage rate in 2019-2020 was 5.3% and the 3-year cumulative coverage rate in 2018-2020 was 7.7%. The corresponding coverage rates of 50-74-year-olds were estimated to be 3.4%, 7.1%, and 10.3%, respectively. Based on the rapid review approach, the overall screening coverage rate for 40-74 years, considering organized screening programs, opportunistic screening, and physical examinations, was then estimated to be 3.0% in China in 2020. However, comparing the findings of this study with the number of health check-ups reported in the local national health statistics yearbooks suggests that the number of CRC physical examinations may be underestimated in this study. The findings suggest that further efforts are needed to improve population access to CRC screening in China. Furthermore, evidence for access to opportunistic CRC screening and physical examination is limited, and more quantitative investigation is needed.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Acessibilidade aos Serviços de Saúde , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Feminino , Masculino , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodosRESUMO
Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.
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Cistanche , Bactérias/genética , Meio Ambiente , Fazendas , Caules de PlantaRESUMO
Background: Cardiovascular implantable electronic devices (CIED) are more and more widely used in the clinical treatment of cardiovascular diseases. However, CIED implantation may also result in a variety of physical, psychological, and social problems among patients. To help patients adapt to life after CIED implantation, it is important to know patients' needs from their perspectives. Explore the needs of CIED patients from their perspectives to guide healthcare providers to improve their quality of life. Methods: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, the VIP database, the Wanfang database, and the China Biomedical Literature database were searched for qualitative studies on the experience of patients with CIED dating from January 2000 to August 2022. The quality of each article was evaluated according to the 2016 edition of the Joanna Briggs Institute Evidence-Based Health Care Center Qualitative Research Quality Evaluation Criteria and an integrative meta-synthesis was undertaken. Results: A total of 18 documents were included, and 111 categories were extracted. Analysis of the data resulted in the identification of 3 themes and 12 subthemes. The first theme, Equipment Symbiosis, included "Mixed feelings about the device as part of the body", "Mixed feelings about the patient's role", and "Mixed feelings about an electrical stimulus". The second theme, External Support, included "Husband and wife relationship damaged", "Eager to participate, unwilling to be overprotected", "Want to return to work but are forced to leave", and "Information supply and demand mismatch". The third theme, Self-coping, included "How to face a doctor", "How to deal with activity restrictions", "How to face yourself", "How to face the future", and "How to face death". Conclusions: Healthcare providers need to accelerate technological innovation and clinical adoption of CIED. Additionally, healthcare providers need to establish a diverse support system led by medical staff, with family members, peers, and society working together, and improve CIEDs remote monitoring to help patients improve their quality of life.
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The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.
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Hipotálamo , Neurônios , Ansiedade , Metabolismo Energético , Neurônios/metabolismoRESUMO
PURPOSE: Gestational diabetes mellitus (GDM) negatively affects the quality of life of pregnant women and is influenced by several factors. Research to date treats pregnant women with gestational diabetes as a homogeneous group based on their quality of life. We attempted to identify subgroups based on self-reported quality of life and explored variables associated with subgroups. METHODS: From September 1, 2020 to November 29, 2020, pregnant women with GDM from two hospitals in Guangdong Province were selected as subjects by convenience sampling method. Medical records provided sociodemographic data, duration of GDM, pregnancy status, and family history of diabetes. Participants completed validated questionnaires for quality of life, anxiety and depression. Latent profile analysis was used to identify profiles of quality of life in pregnant women with GDM, and then a mixed regression method was used to analyze the influencing factors of different profiles. RESULTS: A total of 279 valid questionnaires were collected. The results of the latent profile analysis showed that the quality of life of pregnant women with GDM could be divided into two profiles: C1 "high worry-high support" group (75.6%) and C2 "low worry-low support" group (24.4%). Daily exercise duration and depression degree are negative influencing factors, making it easier to enter the C1 group (p < 0.05). Disease duration and family history of diabetes are positive influencing factors, making it easier to enter the C2 group (p < 0.05). CONCLUSION: The quality of life of pregnant women with GDM had obvious classification characteristics. Pregnant women with exercise habits and depression are more likely to enter the "high worry-high support" group, and health care providers should guide their exercise according to exercise guidelines during pregnancy and strengthen psychological intervention. Pregnant women with a family history of diabetes and a longer duration of the disease are more likely to fall into the "low worry-low support" group. Healthcare providers can strengthen health education for them and improve their disease self-management abilities.
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Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/psicologia , Gestantes , Qualidade de Vida , Exercício FísicoRESUMO
AIM: To explore why young- and middle-aged adults ignore prodromal myocardial infarction symptoms from a life course and sociocultural perspective. DESIGN: A qualitative descriptive study. METHODS: We applied purposeful sampling to recruit participants from a tertiary hospital in Guangzhou from July to November 2021. Face-to-face interviews were performed. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods. RESULTS: Twenty-four young- and middle-aged adults diagnosed with acute myocardial infarction participated in this study. Analysis revealed three main themes: I'm still young, it will not happen to me; to be somebody and different roles, multiple pressures. Age-related self-confidence led to inappropriate perceptions and responses to prodromal symptoms among young- and middle-aged adults. These individuals strived to align their behaviours and attention with social expectations and self-expectations, underestimating the importance of perceiving the warning signs of acute myocardial infarction and seeking medical treatment. Pressure from social roles also prevented them from paying enough attention to prodromal symptoms. CONCLUSION: Targeted social support, public education and technologies should be provided to these individuals since they are pillars of the family and society. We also highlight how nurses can function these strategies appropriately. IMPACTS: This study contributes to a better understanding of the neglect of prodromal symptoms among young- and middle-aged adults. Its results enhance our understanding of the perception of and coping with prodromal symptoms among this population, which will help avoid the burden caused by acute myocardial infarction. PATIENT OR PUBLIC CONTRIBUTION: The patients involved in our study shared their experiences and insights to provide new perspectives regarding the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.
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Infarto do Miocárdio , Sintomas Prodrômicos , Pessoa de Meia-Idade , Adulto , Humanos , Infarto do Miocárdio/diagnóstico , Pesquisa QualitativaRESUMO
Palmitoyl protein thioesterase 1(PPT1) is a lysosomal enzyme that catalyzes the protein depalmitoylation. It is considered to play a crucial role in regulating lysosomes, mitochondria and lipid metabolism. PPT1 has been reported to play an important role in the occurrence and progression of diseases, such as neurological diseases and cancers. However, the regulatory mechanisms remain unknown. In this review, we summarize the progress of PPT1 function and mechanisms in neurological disorders and cancers, which will provide as reference and guidance for exploring the regulatory mechanisms of PPT1 and developing new drugs for treating related diseases in the future.
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Neoplasias , Humanos , Homeostase , Lisossomos , Proteínas de Membrana , Tioléster Hidrolases/genéticaRESUMO
BACKGROUND: While single-method studies have reported on the effectiveness of simulated interprofessional teaching, our understanding of its full effects remains incomplete. Teaching design also provides no relevant theoretical guidance, which reduces the scientific quality and rigor of research. The purpose of this work was to study the effects of the simulated interprofessional education (SIPE) teaching model based on the 3P theory on the course of "Clinical Critical Thinking Training" through a convergent mixed method, and to provide the basis for future teaching design. METHODS: A convergent mixed-method design was used, which consisted of a survey and a semi-structured interview. Data collection took place from September 2021 to July 2022. A cluster sampling method was used to select 60 full-time nursing students from a school in China, and randomly divide them into a control group of 36 and an experimental group of 24. According to the principle of voluntary participation, 6 students majoring in clinical medicine and 6 students majoring in pharmacy were recruited to join the experimental group to form an interprofessional team. The students studied "Clinical Critical Thinking Training" together, in which the control group used traditional simulation teaching and the experimental group used SIPE. The CCTDI (California Critical Thinking Disposition Inventory) and AITCS-II Student (Assessment of Interprofessional Team Collaboration in Student Learning Scale) were used for quantitative evaluation before and after the course, and descriptive statistics and Mann-Whitney U test were used to compare the critical thinking and interprofessional collaboration skills of the two groups of students. Semi-structured interviews were used for qualitative evaluation. Thematic analysis was used to understand student development on the basis of inter-professional core competencies and learning experience. RESULTS: The students' interprofessional cooperation abilities and critical thinking scores improved compared with the beginning of the course, but the scores of the experimental group were significantly higher than the control group (p < 0.05). Three themes emerged regarding simulated interprofessional teaching: clarifying team positioning, improving team efficiency, and optimizing the learning experience. CONCLUSION: SIPE can build students' critical thinking, teamwork, and interprofessional core competencies, which makes it a useful teaching design.
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OBJECTIVES: To evaluate the diagnostic value and reproducibility of T2 mapping versus apparent diffusion coefficients (ADC) for identifying malignant lymph nodes in patients with non-mucinous rectal adenocarcinoma. METHODS: High-resolution magnetic resonance imaging, diffusion-weighted imaging, and T2 mapping were performed on patients with suspected metastatic lymph nodes in the mesorectum or around the superior rectal artery with a short-axis diameter of 4-10 mm. The T2 and ADC values of pathology-confirmed metastatic versus non-metastatic lymph nodes were compared using the independent-samples t test and receiver operating characteristic curves. Intra- and inter-observer reproducibility were tested. The cutoff value for T2 relaxation time was determined. RESULTS: In total, 67 lymph nodes underwent histological analysis, with 24 in the non-metastatic and 43 in the metastatic groups. Intra- and inter-observer agreements for T2 values were 0.999 and 0.998, respectively, which were higher than the ADC values of 0.924 and 0.844, respectively. The mean T2 and ADC values for metastatic lymph nodes (65 ± 7.8 ms and 1.17 ± 0.16 × 10-3 mm2/s, respectively) were significantly lower than for benign lymph nodes(83 ± 5.7 ms and 1.29 ± 0.15 × 10-3 mm2/s, respectively). T2 values had a higher AUC value of 0.990 than the AUC value for ADC of 0.729. With a cutoff value of 77 ms, sensitivity and specificity for T2 values were 95% and 96%, respectively. CONCLUSIONS: T2 mapping had higher diagnostic efficacy and reproducibility than ADC and may be useful in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. KEY POINTS: ⢠Mean T2 values were significantly shorter for malignant versus benign LNs in patients with non-mucinous rectal adenocarcinoma. ⢠The diagnostic efficacy and reproducibility of T2 values were excellent and superior to ADC values.
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Linfonodos , Neoplasias Retais , Imagem de Difusão por Ressonância Magnética , Estudos de Viabilidade , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Curva ROC , Neoplasias Retais/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with high mortality. The incidence of HCC is increasing in China. Abnormal activation of glucose-6-phosphate dehydrogenase (G6PD) exists in all malignant tumors, including HCC, and is closely related to the development of HCC. In addition, the differential expression of non-coding RNAs is closely related to the development of HCC. This systematic review focuses on the relationship between G6PD, HCC, and non-coding RNA, which form the basis for the circRNA/miRNA/G6PD axis in HCC. The circular RNA (circRNA)/microRNA (miRNA)/G6PD axis is involved in development of HCC. We proposed that non-coding RNA molecules of the circRNA/miRNA/G6PD axis may be novel biomarkers for the pathological diagnosis, prognosis, and targeted therapy of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genéticaRESUMO
OBJECTIVES: This study aims to evaluate diagnostic performance of radiomic analysis using computed tomography (CT) to identify lymphovascular invasion (LVI) in patients diagnosed with rectal cancer and assess diagnostic performance of different lesion segmentations. METHODS: The study is applied to 169 pre-treatment CT images and the clinical features of patients with rectal cancer. Radiomic features are extracted from two different volumes of interest (VOIs) namely, gross tumor volume and peri-tumor tissue volume. The maximum relevance and the minimum redundancy, and the least absolute shrinkage selection operator based logistic regression analyses are performed to select the optimal feature subset on the training cohort. Then, Rad and Rad-clinical combined models for LVI prediction are built and compared. Finally, the models are externally validated. RESULTS: Eighty-three patients had positive LVI on pathology, while 86 had negative LVI. An optimal multi-mode radiology nomogram for LVI estimation is established. The area under the receiver operating characteristic curves of the Rad and Rad-clinical combined model in the peri-tumor VOI group are significantly higher than those in the tumor VOI group (Rad: peri-tumor vs. tumor: 0.85 vs. 0.68; Rad-clinical: peri-tumor vs. tumor: 0.90 vs 0.82) in the validation cohort. Decision curve analysis shows that the peri-tumor-based Rad-clinical combined model has the best performance in identifying LVI than other models. CONCLUSIONS: CT radiomics model based on peri-tumor volumes improves prediction performance of LVI in rectal cancer compared with the model based on tumor volumes.
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Neoplasias Retais , Humanos , Nomogramas , Prognóstico , Neoplasias Retais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Cone-rod dystrophy (CORD) is an inherited retinal degenerative disease characterized by progressive loss of cone and rod photoreceptors. Although several genes have been reported to cause autosomal dominant CORD (adCORD), the genetic causes of adCORD have not been fully elucidated. Here, we identified the ATP1A3 gene, encoding the α3 subunit of Na+, K+-ATPase, as a novel gene associated with adCORD. Using whole-exome sequencing (WES), we found a candidate mutation of ATP1A3 that co-segregated with the disease in an analysis of two affected patients and one healthy relative in an adCORD family. According to our RNA-seq data, we demonstrated that the Atp1a3 mRNA level was extremely high in the murine retina. Overexpression of mutant ATP1A3 in vitro led to a reduced oxygen consumption rate (OCR), reflecting the limited mitochondrial reserve capacity. Furthermore, we generated transgenic mice expressing the ATP1A3 cDNA with patient variant and found decreased electroretinogram (ERG) responses. Moreover, the mutant ATP1A3 is highly expressed in photoreceptor inner segment, where mitochondria are enriched. These results suggest that the ATP1A3 mutation is a new genetic cause responsible for adCORD and indicate that ATP1A3 plays an important role in retinal function.
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Distrofias de Cones e Bastonetes/genética , Genes Dominantes/genética , Mutação/genética , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Animais , Linhagem Celular Tumoral , Eletrorretinografia/métodos , Feminino , Células HeLa , Humanos , Masculino , Camundongos , Linhagem , Fenótipo , Retina/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/genética , Células Fotorreceptoras Retinianas Bastonetes/patologia , Retinose Pigmentar/genética , Acuidade Visual , Sequenciamento do Exoma/métodos , Adulto JovemRESUMO
The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5+ or MYC+ or CD5-MYC- patients. Furthermore, patients with DECM showed a similar outcome to MYC+BCL2+ lymphoma patients who have extremely poor survival rates. Multivariate analysis demonstrated that DECM was a significant independent predictor for overall survival (Pâ¯<â¯.0001) and progression-free survival (Pâ¯<â¯.0001) in DLBCL. DLBCL patients with DECM showed significantly inferior clinical outcomes compared to the CD5+, MYC+ or CD5-MYC- patients. Combinational therapeutic modalities might be a candidate approach to improve the prognosis of these patients.
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Antígenos CD5/genética , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Idoso , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. METHODS: We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/ ). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). RESULTS: By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P < 0.001), TNM-EC (P = 0.001) in training cohort and TNM-GC (P < 0.001) TNM-EC (P < 0.001) in the validation cohort were both independent prognostic factors. The C-index value for the TNM-GC scheme was larger than that of TNM-EC system in both training (0.721 vs. 0.690, P < 0.001) and validation (0.721 vs. 0.696, P < 0.001) cohorts. After stratification analysis for Siewert type II, the C-index for TNM-GC scheme was still larger than that of TNM-EC in both training (0.724 vs. 0.694, P = 0.005) and validation (0.723 vs. 0.699, P < 0.001) cohorts. CONCLUSIONS: The 8th TNM-GC scheme is superior to TNM-EC in predicting the prognosis of AEG especially for type II among patients underwent transhiatal approaches.
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Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Estadiamento de Neoplasias/normas , Neoplasias Gástricas/patologia , Adenocarcinoma/classificação , Adenocarcinoma/cirurgia , China , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/cirurgia , Esofagectomia , Junção Esofagogástrica/cirurgia , Feminino , Seguimentos , Gastrectomia , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
OBJECTIVE: To explore the role of bone marrow mesenchymal stem cells (BMSC)ï¼an essential element of the bone marrow microenvironment, in multidrug resistance(MDR) of K562 cells, as well as the reversal effect of tetrandrine (TET) on BMSC-mediated MDR and its potential mechanism. METHODS: A mixed co-culture system and a transwell co-culture system for BMSC and K562 cells were established, and the cells were divided into different groups and treated with daunorubicin (DNR) alone or combined with TET and DNR. The CCK-8 assay was used to detect the proliferation of K562 cells in each group, and the cell inhibition rate was calculated. Cytometric bead array (CBA) was used to detect the expression levels of IFN, IL-2, IL-6 and IL-10 in the supernatant of different groups. RT-qPCR and Western blot were used to detected the expression of STAT3 at mRNA and protein levels, respectively. RESULTS: Compared with K562+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR group was significantly decreased (P < 0.05), while the levels of IL-6 in the culture supernatant and phosphorylated STAT3 in K562 cells were significantly increased (P < 0.05). Compared with K562+BMSC+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR+TET group was significantly increased (P < 0.05), while the level of IL-6 and phosphorylated STAT3 was significantly decreased (P < 0.05). CONCLUSION: BMSC can promote the drug resistance of leukemia cells, and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.
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Benzilisoquinolinas , Leucemia , Humanos , Interleucina-6 , Resistencia a Medicamentos Antineoplásicos , Benzilisoquinolinas/farmacologia , Benzilisoquinolinas/uso terapêutico , Daunorrubicina/farmacologia , Células K562 , Leucemia/tratamento farmacológico , Microambiente TumoralRESUMO
The competition among drugs for binding to plasma proteins is regarded as a pharmacokinetic drug interaction. Competition between antitumor agents and other drugs for plasma protein binding can alter the free concentration of the drug, potentially impacting its efficacy and increasing the risk of toxic side effects. Through a range of spectroscopic techniques, this study examined the interaction between limonin and human serum albumin (HSA) in the context of berberine (Ber) and curcumin (Cur) under physiological conditions to clarify the binding mechanisms of binary and ternary systems at the molecular level. As demonstrated by fluorescence quenching experiments, Static quenching was identified as the mechanism of interaction between HSA and limonin. The results of site competition experiments indicated that the binding site between limonin and HSA was site I, a result further supported by molecular docking simulations. Through the use of thermodynamic data calculations, it was determined that limonin forms a stable complex with HSA by establishing hydrogen bonds and van der Waals forces. Circular dichroism (CD) spectroscopy, three-dimensional (3D) fluorescence spectroscopy, and synchronous fluorescence spectroscopy (SFS) employed to validate the notion that limonin perturbed the microenvironment of amino acids and induced conformational changes in HSA. What's more, the presence of Ber or Cur was found to have further modified the alterations observed in the interaction between the original HSA-limonin binary system. In vitro cellular experiments showed that interaction with HSA reduced the antitumor activity of limonin. In contrast, adding Ber or Cur increased the inhibition rate of tumor cells. The coexistence of both Ber and Cur significantly diminished limonin's binding affinity to HSA. The current investigation enhances comprehension regarding the binding characteristics and interaction mechanisms involving limonin, Ber, Cur, and HSA. It explores the potential of HSA as a versatile drug carrier and furnishes theoretical underpinnings for co-administrative strategies.
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AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.
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Urinary tract infections (UTIs) are prevalent and recurrent bacterial infections that affect individuals worldwide, posing a significant burden on healthcare systems. The present study aimed to explore the epidemiology of UTIs, investigating the seasonal, gender-specific and age-related bacterial pathogen distribution to guide clinical diagnosis. Data were retrospectively collected from electronic medical records and laboratory reports of 926 UTIs diagnosed in Fuding Hospital (Fujian University of Traditional Chinese Medicine, Fuding, China). Bacterial isolates were identified using standard microbiological techniques. χ2 tests were performed to assess associations between pathogens and the seasons, sex and age groups. Significant associations were found between bacterial species and seasons. Enterococcus faecium exhibited a substantial prevalence in spring (χ2, 12.824; P=0.005), while Acinetobacter baumannii demonstrated increased prevalence in autumn (χ2, 16.404; P=0.001). Female patients showed a higher incidence of UTIs. Gram-positive bacteria were more prevalent in males, with Staphylococcus aureus showing significant male predominance (χ2, 14.607; P<0.001). E. faecium displayed an age-related increase in prevalence (χ2, 17.775; P<0.001), whereas Escherichia coli tended to be more prevalent in younger patients (χ2, 12.813; P=0.005). These findings highlight the complex nature of UTIs and offer insights for tailored diagnostic and preventive strategies, potentially enhancing healthcare outcomes.
RESUMO
BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.