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This meta-analysis aimed to compare the efficacy of robot-assisted vs. laparoscopic adrenalectomy in individuals with obesity. We performed an extensive review of the PubMed, Embase, and Cochrane Library databases for research on adrenalectomy in individuals with obesity up to August 2024. Only studies comparing robot-assisted surgery with laparoscopic surgery were included. Only articles written in English were included. We utilized established criteria for inclusion and exclusion, concentrating on randomized controlled trials and cohort studies. The ROBINS-I instrument was employed to assess the bias risk in non-randomized control studies. Review Manager 5.4.1 was utilized to conduct the meta-analysis. The final analysis incorporated four retrospective cohort studies with a total of 492 individuals with obesity (261 receiving RA and 231 undergoing LA). The results showed that RA was linked to a shorter duration of hospitalization and less estimated blood loss in comparison to LA. Nonetheless, there were no notable distinctions between the two surgical methods in terms of OT, laparotomy conversion rates, overall postoperative complications, or death rates after surgery. In conclusion, RA is a reliable and safe choice for individuals with obesity. It offers notable advantages over LA in terms of LOHS and EBL.
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Adrenalectomia , Laparoscopia , Obesidade , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Adrenalectomia/métodos , Laparoscopia/métodos , Obesidade/complicações , Obesidade/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Masculino , Feminino , Duração da CirurgiaRESUMO
BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, Pâ =â .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, Pâ =â .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.
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Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.
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Norovirus (NoV) is a common pathogen that can cause infectious diarrhea. This study aimed to determine the prevalence, clinical features, and genotypes of NoV-associated diarrhea in Wuxi, China. A total of 4,416 stool samples were collected from patients with diarrhea at enteric disease clinics of sentinel hospitals in Wuxi from February 1, 2013 to December 31, 2020. Univariate and Akaike information criterion stepwise logistic regression were used to identify differences as integrated within a clinical setting (NoV positive [+] versus NoV negative [-], NoV+ versus rotavirus [RV]+, NoV+ versus bacteria+, genogroup [G] I and GII genotypes). Norovirus was detected in 9.85% of stool samples, which was greater than other tested pathogens. Excluding coinfection of NoV and other viruses or bacteria, patients infected with NoV had a lower chance of acquiring the virus in summer (P < 0.001; odds ratio [OR], 0.257; 95% CI, 0.189-0.36) when compared with patients without NoV. Patients with diarrhea infected with NoV featured nausea and vomiting (P < 0.001; OR, 2.297, 95% CI, 1.85-2.86) and loose stools (P = 0.006; OR, 2.247; 95% CI, 1.30-4.10), but less abdominal cramping (P = 0.001; OR, 0.676; 95% CI, 0.54-0.84). Patients infected with RV (P < 0.001; OR, 0.413; 95% CI, 0.25-0.68) or bacteria (P < 0.001; OR, 0.422; 95% CI, 0.26-0.67) were more vulnerable to fever than those infected with NoV. A total of 379 GII strains were detected concomitant with 48 GI strains, and there was a seasonal difference between the GI and GII genotypes. Strengthening pathogen detection for infectious diarrhea was helpful for understanding the epidemiological characteristics of infections with NoV and, potentially, for preventing disease outbreaks.
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Infecções por Caliciviridae , Disenteria , Gastroenterite , Norovirus , Rotavirus , Humanos , Lactente , Norovirus/genética , Gastroenterite/epidemiologia , Prevalência , Infecções por Caliciviridae/epidemiologia , Diarreia/epidemiologia , China/epidemiologia , Genótipo , FezesRESUMO
Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.
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Carcinogênese , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Neoplasias , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinogênese/genética , Dano ao DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Neoplasias/genética , Neoplasias/patologiaRESUMO
Streptococcus suis (S. suis) is widely acknowledged as a significant zoonotic pathogen in Southeast Asia and China, which has led to a substantial number of fatalities in both swine and humans. Despite the prevalent use of mice as the primary animal model to study S. suis pathogenesis, the substantial differences in the major histocompatibility complex (MHC) between humans and mice underscore the ongoing exploration for a more suitable and effective animal model. In this study, humanized transgenic HLA-A11/DR1 genotypes mice were used to evaluate the differences between humanized HLA and murine H2 in S. suis infection. Following intravenous administration of S. suis suspensions, we investigated bacterial load, cytokine profiles, pathological alterations, and immune cell recruitment in both Wild-type (WT) and humanized mice across different post-infection time points. Relative to WT mice, humanized mice exhibited heightened pro-inflammatory cytokines, exacerbated tissue damage, increased granulocyte recruitment with impaired resolution, notably more pronounced during the late infection stage. Additionally, our examination of bacterial clearance rates suggests that HLA-A11/DR1 primarily influences cell recruitment and mitochondrial reactive oxygen species (ROS) production, which affects the bacterial killing capacity of macrophages in the late stage of infection. The reduced IL-10 production and lower levels of regulatory T cells in humanized mice could underlie their compromised resolution ability. Intervention with IL-10 promotes bacterial clearance and inflammatory regression in the late stages of infection in transgenic mice. Our findings underscore the heightened sensitivity of HLA-A11/DR1 mice with impaired resolution to S. suis infection, effectively mirroring the immune response seen in humans during infection. The humanized HLA-A11/DR1 mice could serve as an optimal animal model for investigating the pathogenic and therapeutic mechanisms associated with sepsis and other infectious diseases.
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Infecções Estreptocócicas , Streptococcus suis , Humanos , Animais , Camundongos , Suínos , Interleucina-10 , Streptococcus suis/genética , Sorogrupo , Antígeno HLA-A11 , Camundongos Transgênicos , Imunidade , Infecções Estreptocócicas/microbiologiaRESUMO
Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.
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Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Reparo de Erro de Pareamento de DNA/genética , População do Leste Asiático , Neoplasias Colorretais Hereditárias sem Polipose/genéticaRESUMO
Carbapenem-resistant Enterobacteriaceae strains have emerged as a serious threat to global public health. In recent years, blaIMI, a carbapenemase gene that drew less attention before, has been increasingly detected in both clinical and environmental settings. However, the environmental distribution and transmission of blaIMI, especially in aquaculture, require systematic investigation. In this study, the blaIMI gene was detected in fish (n = 1), sewage (n = 1), river water (n = 1), and aquaculture pond water samples (n = 17) collected from Jiangsu, China, demonstrating a relatively high sample-positive ratio of 12.4% (20/161). Thirteen blaIMI-2- or blaIMI-16-carrying Enterobacter asburiae strains were isolated from blaIMI-positive samples of aquatic products and aquaculture ponds. We also identified a novel transposon (Tn7441) carrying blaIMI-16 and a conserved region containing several truncated insertion sequence (IS) elements harboring blaIMI-2, all of which may play important roles in blaIMI mobilization. The occurrence of blaIMI-carrying Enterobacter asburiae in aquaculture-related water samples and fish samples highlights the risk of transmission of blaIMI-carrying strains through the food chain and the need for effective measures to prevent further dissemination. IMPORTANCE IMI carbapenemases have been detected in clinical isolates of many bacterial species with systemic infection and cause a further burden on clinical treatment in China, but their source and distribution are still unclear. The study systematically investigated the distribution and transmission of the blaIMI gene in aquaculture-related water bodies and aquatic products in Jiangsu Province, China, which is famous for its rich water resources and developed aquaculture industry. The relatively high prevalence of blaIMI in aquaculture samples and the identification of novel mobile elements harboring blaIMI enhance our knowledge of blaIMI gene distribution and highlight the public health risk and urgency of surveillance of aquaculture water systems in China.
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[This corrects the article DOI: 10.3389/pore.2022.1610638.].
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Background: Anoikis is a form of programmed cell death or programmed cell death(PCD) for short. Studies suggest that anoikis involves in the decisive steps of tumor progression and cancer cell metastasis and spread, but what part it plays in bladder cancer remains unclear. We sought to screen for anoikis-correlated long non-coding RNA (lncRNA) so that we can build a risk model to understand its ability to predict bladder cancer prognosis and the immune landscape. Methods: We screened seven anoikis-related lncRNAs (arlncRNAs) from The Cancer Genome Atlas (TCGA) and designed a risk model. It was validated through ROC curves and clinicopathological correlation analysis, and demonstrated to be an independent factor of prognosis prediction by uni- and multi-COX regression. In the meantime, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, and half-maximal inhibitory concentration prediction (IC50) were implemented with the model. Moreover, we divided bladder cancer patients into three subtypes by consensus clustering analysis to further study the differences in prognosis, immune infiltration level, immune checkpoints, and drug susceptibility. Result: We designed a risk model of seven arlncRNAs, and proved its accuracy using ROC curves. COX regression indicated that the model might be an independent prediction factor of bladder cancer prognosis. KEGG enrichment analysis showed it was enriched in tumors and immune-related pathways among the people at high risk. Immune correlation analysis and drug susceptibility results indicated that it had higher immune infiltration and might have a better immunotherapy efficacy for high-risk groups. Of the three subtypes classified by consensus clustering analysis, cluster 3 revealed a positive prognosis, and cluster 2 showed the highest level of immune infiltration and was sensitive to most chemistries. This is helpful for us to discover more precise immunotherapy for bladder cancer patients. Conclusion: In a nutshell, we found seven arlncRNAs and built a risk model that can identify different bladder cancer subtypes and predict the prognosis of bladder cancer patients. Immune-related and drug sensitivity researches demonstrate it can provide individual therapeutic schedule with greater precision for bladder cancer patients.
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RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Bexiga Urinária , ApoptoseRESUMO
In 2016, an outbreak of paratyphoid fever occurred in 40 cases at Qingyang town, in China. A case-control study was carried out to determine the source of this outbreak. Case-control study was conducted to identify the risk factors of this outbreak. The cases were identified as patients with isolation of S. Paratyphi, controls were confirmed cases' healthy classmates, colleagues or neighbors and matched by age (±5 y) and gender. Pulsed-field gel electrophoresis was performed to source tracking. Totally, 40 cases were reported: 24 cases were students, and 20 (20/24) of them were Qingyang High School students. For the case-control study, consuming Chinese egg pancakes was detected as a risk factor (OR1:1 = 5.000; 95% CI: 1.710-14.640), and hand-washing before meals was protective behavior compared with seldom hand-washing (OR1:1 = 23.256; 95% CI: 2.451-200.000). S. Paratyphi was cultured from a well water sample used for washing contents of the pancakes. Isolates from well water and paratyphoid cases showed the same PFGE patterns. Contaminated well water and Chinese egg pancakes were likely source and vehicle of this outbreak. Health education, especially handwashing, and food safety supervision should be promoted particularly in schools.
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Febre Paratifoide , Humanos , Febre Paratifoide/epidemiologia , Febre Paratifoide/etiologia , Estudos de Casos e Controles , Surtos de Doenças , China/epidemiologia , ÁguaRESUMO
Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.
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Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Neoplasias da Bexiga Urinária , Feminino , Humanos , Instabilidade de Microssatélites , Receptor de Morte Celular Programada 1 , Reparo de Erro de Pareamento de DNA , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Imunoterapia , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients. OBJECTIVE: Potential therapeutic biomarkers are urgently needed for future clinical treatment. METHODS: We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays. RESULTS: We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes. CONCLUSIONS: Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease.
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This work aimed to characterize a 29-kb blaKPC-2-carrying plasmid, pR31-KPC, from a multidrug resistant strain of Pseudomonas aeruginosa isolated from the sputum of an elderly patient with multiple chronic conditions in China. The backbone of pR31-KPC is closely related to four other blaKPC-2-carrying plasmids, YLH6_p3, p1011-KPC2, p14057A, and pP23-KPC, none of which have been assigned to any of the known incompatibility groups. Two accessory modules, the IS26-blaKPC-2-IS26 unit and IS26-ΔTn6376-IS26 region, separated by a 5.9-kb backbone region, were identified in pR31-KPC, which was also shown to carry the unique resistance marker blaKPC-2. A comparative study of the above five plasmids showed that p1011-KPC2 may be the most complete plasmid of this group to be reported, while pR31-KPC is the smallest plasmid having lost most of its conjugative region. Regions between the iterons and orf207 in the backbone may be hot spots for the acquisition of exogenous resistance entities. The accessory regions of these plasmids have all undergone several biological events when compared with Tn6296. The further transfer of blaKPC-2 in these plasmids may be initiated by either the Tn3 family or IS26-associated transposition or homologous recombination. The data presented here will contribute to a deeper understanding of blaKPC-2 carrying plasmids in Pseudomonas.
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OBJECTIVES: Some studies have identified tumour-infiltrating lymphocytes (TILs) in H&E-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between H&E-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Library, PubMed and Embase databases were searched through 25 February 2020. ELIGIBILITY CRITERIA: Studies evaluating the correlations between TILs assessed by H&E-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included. DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively. RESULTS: We enrolled nine studies including 2835 cases for the present meta-analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3-T4 vs T1-T2) (RR=0.58, 95% CI 0.50 to 0.66, p<0.001), less lymph node involvement (presence vs absence) (RR=0.68, 95% CI 0.56 to 0.81, p<0.001) and earlier TNM (tumour, node, metastasis) stage (III-IV vs I-II) (RR=0.68, 95% CI 0.55 to 0.83, p<0.001). TIL density was not associated with age, gender, Lauren classification or histological grade. The methodology for evaluating TIL and its cut-off value varied across different studies, which might affect the results of our meta-analysis. CONCLUSIONS: Our meta-analysis suggests that H&E-based TIL density is a reliable biomarker to predict the clinical outcomes of patients with gastric cancer. Multicentre, prospective studies are needed to further confirm our findings. PROSPERO REGISTRATION NUMBER: CRD42020169877.
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Linfócitos do Interstício Tumoral , Neoplasias Gástricas , Idoso , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologiaRESUMO
A multiplex PCR (mPCR) assay was established to detect five pathogenic Vibrio species and Plesiomonas shigelloides. Twelve genes were included: ompW, ctxA, rfbN, and wbfR from V. cholerae; tl, tdh, and trh from V. parahaemolyticus; toxR and vmhA from V. mimicus; toxR from V. fluvialis; vvhA from V. vulnificus; and the 23S rRNA gene from P. shigelloides. The specificity of the mPCR assay was 100% for the detection of 136 strains and the limits of detection (LoD) were 12.5-50 pg/reaction. The assay exhibited higher sensitivity than cultivation methods in the detection of APW cultures of 113 diarrhea samples. In the analysis of 369 suspected Vibrio populations from estuarine water samples, the specificity of the mPCR for V. cholerae and V. parahaemolyticus was 100% for both, while the sensitivities were 100% and 96.1%, respectively. The assay can be applied to screen enrichment cultures and suspected colonies from environmental and clinical samples.
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Reação em Cadeia da Polimerase Multiplex/métodos , Plesiomonas/genética , Plesiomonas/isolamento & purificação , Vibrio/genética , Vibrio/isolamento & purificação , Eletroforese Capilar , Estuários , Humanos , Sensibilidade e Especificidade , Microbiologia da ÁguaRESUMO
Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, varies across malignancies. Panel sequencing-based estimates of TMB have largely replaced whole-exome sequencing-derived TMB in the clinic. Retrospective evidence suggests that TMB can predict the efficacy of immune checkpoint inhibitors, and data from KEYNOTE-158 led to the recent FDA approval of pembrolizumab for the TMB-high tumor subgroup. Unmet needs include prospective validation of TMB cutoffs in relationship to tumor type and patient outcomes. Furthermore, standardization and harmonization of TMB measurement across test platforms are important to the successful implementation of TMB in clinical practice. SIGNIFICANCE: Evaluation of TMB as a predictive biomarker creates the need to harmonize panel-based TMB estimation and standardize its reporting. TMB can improve the predictive accuracy for immunotherapy outcomes, and has the potential to expand the candidate pool of patients for treatment with immune checkpoint inhibitors.
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Biomarcadores Tumorais/metabolismo , Neoplasias/genética , Carga Tumoral/genética , HumanosRESUMO
OBJECTIVE: To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa). METHODS: We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6ï¼76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups. RESULTS: After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ï¼»3.77 ± 4.14ï¼½ vs ï¼»5.96 ± 7.01ï¼½ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (ï¼»5.19 ± 2.83ï¼½ vs ï¼»6.52 ± 3.34ï¼½ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P < 0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P < 0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P > 0.05) or between the two groups before and after treatment (P > 0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (ï¼»37.29 ± 15.73ï¼½ vs ï¼»29.41 ± 14.37ï¼½ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105). CONCLUSIONS: Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.
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Inibidores da Angiogênese , Braquiterapia , Radioisótopos do Iodo , Neoplasias da Próstata , Inibidores da Angiogênese/administração & dosagem , Terapia Combinada/normas , Humanos , Estimativa de Kaplan-Meier , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Based on one year real-time measurements from a seven-wavelength Aethalometer combined with an Aethalometer model, the measured aerosol absorption coefficients at different wavelengths have been used to apportion the contribution of fossil fuel and biomass burning sources to the total black carbon (BC) mass concentration in the north suburb of Nanjing. Good consistency in the relationship between the Angstrom absorption exponent(α)and the ratio of BC from biomass burning sources to total BC (BB) was obtained during this period. The α was highest in winter and lowest in summer, which indicates the change in the source of the absorbing aerosols and their relative source strength. The BC and the BC from fossil fuel (BCff) and biomass burning (BCbb) mass concentrations exhibit significant diurnal variation, with higher values during 07:00 to 09:00 (local time) and 18:00 to 21:00. The BCff was three to five times higher than the BCbb and contributes greatest to the BC mass concentrations throughout the day. Night time BC values were about a factor of 1.2 higher than day time BC values. Meanwhile, the concentration weighted trajectory (CWT) analysis indicates that the highest value of BC was concentrated in the Zhejiang, Anhui, Jiangxi, and Fujian provinces.
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Using a wide-range particle spectrometer (WPS), an environmental management system (EMS), KC-120H middle volume sampler, a 850 professional ion chromatography analyzer, and heat/light carbon analyzer (DRI2001A), we observed the number concentration of aerosols with sizes ranging from 10 nm to 10 µm, gas concentrations, and concentrations of PM2.5, water-soluble ions, OC, and EC in a Lin'an atmospheric background station from January 9 to 31, 2015. The positive matrix factorization (PMF) model was applied for source apportionment, and the size distribution and diurnal variations of emission sources were analyzed based on the meteorological data. The average aerosol concentration was 5062 cm-3·nm-1 and PM2.5 mass concentration was 123.6 µg·m-3. The average concentrations of NO3-, SO42-, and NH4+, the main water-soluble ions in PM2.5 were 19.2, 15.4, and 10.8 µg·m-3, which accounted for 37.9%, 30.4%, and 21.4% of total water-soluble ions, respectively. Theaverage concentrations of OC and EC were 24.4 µg·m-3 and 6.6 µg·m-3. Secondary aerosol formation, coal combustion, motor vehicle emissions, dust, andbiomass burning were the main sources of PM2.5 in Lin'an during winter with contributions of 42.3%, 21.4%, 17.1%, 8.7%, and 10.6%, respectively. Different sources had different aerosol number concentration distributions. The aerosol number concentration spectra of secondary sources, vehicle emissions, dust, and biomass burning followed unimodal-type distributions with peaks at 120, 50, 100, and 90 nm. Coal particle number concentration was a bimodal distribution which exhibited peak values at 25 nm and 100 nm (19842 cm-3·nm-1 and 18372 cm-3·nm-1, respectively). The spectra of surface concentrations of secondary sources, coal combustion, motor vehicle emissions, dust, and biomass burning followed a three-peak distribution. The peaks were at 650, 210, 160, 180, and 575 nm. The diurnal variations of particle number concentrations influenced by diurnal variations in the boundary layer and human activities were consistent with the variations in surface concentrations, which displayed bimodal-type distribution.