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Background: Currently, there are few studies on immune-related prognostic analysis of hepatocellular carcinoma (HCC). Our aim was to establish an immune-correlated prognostic model for HCC. Methods: Immune-associated cells were obtained from the scRNA-seq dataset (GSE149614) of HCC. Differentially expressed genes between normal and tumor cells from immune-associated cells and the immune-related genes from the ImmPort database were used to identify immune-related differentially expressed genes (IRDEGs). Subsequently, the risk model was established in the TCGA-LIHC cohort (n = 438) from the Cancer Genome Atlas (TCGA) database by using Kaplan-Meier (K-M) survival curve, univariate/multivariate Cox regression analysis. Subsequently, we further analyzed tumor immune microenvironment characteristics, somatic mutation, immune checkpoint and its ligand expression levels between high- and low-risk groups, as well as drug sensitivity prediction. ICGC cohort was set as the validation cohort. TCGA-LIHC cohort and three independent the Gene Expression Omnibus (GEO) datasets (GSE54236, GSE14520, and GSE64041) was used to verify IRDEGs expression, as well as PCR assays using clinical samples. Results: The IRDEGs was composed of 4 genes, namely B2M, SPP1, PPIA, and HRG. The 438 HCC patients were divided into high- and low-risk group. The high-risk group was associated with poor prognosis, including higher T stage, advanced pathological stages, less immune cell infiltration, higher TP53 mutation rate, the high expression of CTLA4 and HAVCR2. Besides, high-risk populations benefit from most chemotherapy drugs. Similarly, the performance of the risk model was validated in the ICGC. All four datasets (TCGA-LIHC cohort, GSE54236, GSE14520, and GSE64041) and clinical q-PCR results demonstrated that, compared with normal samples, the expressions of B2M and HRG were lower in tumor samples, and the expression of SPP1 was higher. Conclusion: In summary, the immune-related prognostic signature had a good predictive performance on prognosis and immunotherapy for HCC patients.
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BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.
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BACKGROUND: This study was to explore the causal associations of sleep traits including sleep duration, snoring, chronotype, sleep disorders, getting up in the morning, sleeplessness/insomnia and nap during day with the risk of thyroid cancer based on Mendelian randomization (MR) analysis. METHOD: Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published genome-wide association studies (GWASs) using the FinnGen and UK Biobank databases. A series of screening processes were performed to select qualified SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the Mendelian Randomization robust adjusted profile score (MR-RAPS), the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and the Weighted Median to estimate the causal links between sleep traits and the risk of thyroid cancer. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: The IVW results showed that getting up in the morning (OR = 0.055, 95%CI: 0.004-0.741) and napping during day (OR = 0.031, 95%CI: 0.002-0.462) were associated with decreased risk of thyroid cancer in the Italian population. A 1.30-h decrease of sleep duration was associated with 7.307-fold of thyroid cancer risk in the Finnish population (OR = 7.307, 95%CI: 1.642-32.519). Cronotype could decrease the risk of thyroid cancer in the Finnish population (OR = 0.282, 95%CI: 0.085-0.939). Sleep disorders increased the risk of thyroid cancer in the Finnish population (OR = 2.298, 95%CI: 1.194-4.422). The combined results revealed that sleep duration was correlated with increased risk of thyroid cancer (OR = 5.600, 95%CI: 1.458-21.486). CONCLUSION: Decreased sleep duration was associated with increased risk of thyroid cancer, which indicated the importance of adequate sleep for the prevention of thyroid cancer.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Sono , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/epidemiologia , Fatores de Risco , Predisposição Genética para Doença , Transtornos do Sono-Vigília/genética , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/complicaçõesRESUMO
Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.
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DNA Viral , Vírus da Hepatite B , Hepatite B Crônica , Fígado , Humanos , Hepatite B Crônica/patologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Masculino , Feminino , DNA Viral/sangue , Adulto , Fígado/patologia , Fígado/virologia , Estudos Retrospectivos , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Pessoa de Meia-Idade , Carga Viral , Biópsia , Tolerância Imunológica , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Cirrose Hepática/imunologia , Adulto JovemRESUMO
PURPOSE: To review the resections of endolymphatic sac tumor (ELST) and describe our experience in the surgical management of ELST. METHODS: Retrospective investigation of consecutive patients who underwent resection of ELSTs at our hospital between 1999 and 2019. The symptoms, diagnosis, surgical findings, and outcomes were analyzed to develop a tumor staging system and corresponding surgical strategy. RESULTS: Retrospective review revealed the surgical treatment of 22 ELSTs. Based on intraoperative findings of tumor extent and size, ELSTs were classified into two types. Type-I (n = 6) referred to the small tumors that were locally confined with limited invasion of semicircular canals and dura; type-II (n = 16) referred to the large tumors that presented extensive erosion of at least one anatomic structure apart from the semicircular canals and the dura around endolymphatic sac. In this case series, Type-I ELST is amenable to resection through a transmastoidal approach, and subtotal petrosectomy is appropriate for the resection of type-II ELST. Sensorineural hearing loss (SNHL) is the most commonly preoperative symptom in both two types of cases. Five type-II ELSTs experienced recurrence and underwent reoperation, whereas all type-I ELSTs did not. CONCLUSION: ELST usually results in SNHL (95%) at the time of diagnosis. The surgical strategy and prognosis of ELST resections are different between type-I and type-II: type-I ELST is amenable to transmastoidal approach with the preservation of facial nerve, whereas type-II ELST increase the surgical difficulty and the risk of recurrence, and subtotal petrosectomy is the basic requirement for the resection of type-II ELST.
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Neoplasias da Orelha , Saco Endolinfático , Perda Auditiva Neurossensorial , Doenças do Labirinto , Doença de von Hippel-Lindau , Humanos , Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/cirurgia , Saco Endolinfático/cirurgia , Saco Endolinfático/patologia , Doenças do Labirinto/cirurgia , Estudos Retrospectivos , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/patologia , Doença de von Hippel-Lindau/cirurgiaRESUMO
Background: There is little evidence exploring prognostic effects of surgery and radiotherapy on adenoid cystic carcinoma (ACC) of the head and neck. This study sought to evaluate the prognostic effects of surgery or radiotherapy on ACC of the salivary gland, oropharynx, and nose, nasal cavity, and middle ear. Methods: In this cohort study, the data of 2,392 participants with ACC of the head and neck were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Participants were divided into the salivary gland group (n=1,351), the mouth and oropharynx group (n=563), and the nose, nasal cavity, and middle ear group (n=478). Baseline characteristics were assessed via questionnaires or laboratory analysis and outcome variables were all-cause death and cancer-specific death of patients. Baseline data were collected in 2004, and patients were followed-up to 2016. The survival time of patients were recorded. Univariate and multivariate Cox regression analyses explored the effects of surgery and radiotherapy on overall prognosis of ACC patients. Fine-Gray test assessed the effects of surgery and radiotherapy on cancer-specific mortality of ACC patients. Results: In total, 766 died and 1,626 survived with a median survival time of 9.92 years. After adjusting for confounders, patients with ACC of the salivary gland who underwent surgery had a decreased risk of all-cause mortality [hazard ratio (HR) =0.51; 95% confidence interval (CI): 0.36-0.71] and cancer-specific mortality (HR =0.57; 95% CI: 0.34-0.97). Surgery was found to be a protective factor for the risk of all-cause mortality (HR =0.47; 95% CI: 0.28-0.78) and cancer-specific mortality (HR =0.70; 95% CI: 0.33-1.50) of patients with ACC of the mouth and oropharynx after adjusting for confounders. After adjusting for confounders, patients with ACC of the nose, nasal cavity, and middle ear who underwent surgery had a decreased risk of all-cause mortality (HR =0.46; 95% CI: 0.30-0.70) and cancer-specific mortality (HR =0.35; 95% CI: 0.20-0.61). Conclusions: Surgery was associated with a decreased risk of mortality in patients with ACC of the salivary gland, oropharynx, and nose, nasal cavity, and middle ear, which suggested the value of surgery for improving their prognosis.
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Background: Patients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC. Methods: Genes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined. Results: The detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells. Conclusion: The response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.
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The members of the glutathione S-transferase (GST) superfamily often exhibit functional overlap and can compensate for each other. Their concentrations in serum are considered as disease biomarkers. A global and quantitative evaluation of serum GSTs is therefore urgent, but there is a lack of efficient approaches due to technological limitations. GSH magnetic beads were examined for their affinity to enrich GSTs in serum, and the enriched GSTs were quantitatively targeted using a Q Exactive HF-X mass spectrometer in parallel reaction monitoring (PRM) mode. To optimize the quantification of GST peptides, sample types, trypsin digestion, and serum loading were carefully assessed; a biosynthetic method was employed to generate isotope-labeled GST peptides, and instrumental parameters were systematically optimized. A total of 134 clinical sera were collected for GST quantification from healthy donors and patients with four liver diseases. Using the new approach, GSTs in healthy sera were profiled: 14 GST peptides were quantified, and the abundance of five GST families was ranked GSTM > GSTP > GSTA > MGST1 > GSTT1, ranging from 0.1 to 4 pmol/L. Furthermore, combining the abundance of multiple GST peptides could effectively distinguish different types of liver diseases. Quantification of serum GSTs through targeted proteomics, therefore, has apparent clinical potential for disease diagnosis.
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Glutationa Transferase , Espectrometria de Massas em Tandem , Cromatografia Líquida , Glutationa , Glutationa Transferase/análise , Humanos , Fígado , Peptídeos , Proteômica/métodosRESUMO
OBJECTIVE: To update the recognition of the trends in the incidence of childhood thyroid cancer (TC) and its prognosis. METHODS: A large-scale sample based on long time-line public database was recruited. Join-point regression model was used to analyze the incidence trend of childhood TC. Univariable and multivariable Cox regression model analyses were applied to explore the survival situation and prognostic factors. RESULTS: The incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95% CI 2.6-5.5) to 11.5/million (95% CI 9.2-14.1), AAPC = 2.38% (95% CI 1.98-9.65) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975-2005) increased slowly (APC = 1.08%, 95% CI 0.38-1.82) while Trend2 (2005-2016) increased dramatically (APC = 6.77%, 95% CI 4.30-9.28). Annual incidence rate of small size tumor (< 4 cm) and local stage childhood TC increased significantly. The overall cumulative survival rate for childhood TC was high up to 97-99%. Males, black race, MTC type, distant metastasis, tumor size ≥ 4 cm, non-primary cancer were the independent risk factors of childhood TC prognosis. CONCLUSION: A contribution of overdetection to rising pediatric TC rates might not be able to rule out. For clinical implications, screening TC in children with potential specific risk factors is feasible. Over-treatment to small size and local stage TC in children should be avoided.
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Neoplasias da Glândula Tireoide , Criança , Humanos , Incidência , Masculino , Prognóstico , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/epidemiologiaRESUMO
Objective:To explore the clinical feature and surgical treatment of patients with parapharyngeal space tumors. Method:A retrospective review of 214 cases with parapharygeal space tumors treated. The data on clinical manifestations, imaging examinations, pathological types, surgical approach, and postoperative complications were reviewed. Result:Of the 214 cases, the tumor was benign in nature in 135 casesï¼63.1%ï¼ and malignant in 79 casesï¼36.9%ï¼. There was no gender difference in the incidence of benign tumors, and the ratio of male to female was 1:1. The incidence of malignant tumors was higher in males than in females, and the ratio was 3.3:1. Regardless of benign and malignant tumors, the high incidence age is 40-59. Two-thirds of cases of parapharyngeal space tumors had different degrees of peripheral structural invasion. The most common cases involving the skull base were 76 casesï¼35.5%ï¼, followed by blood vessels and nerves, 24 casesï¼11.2%ï¼ and 16 casesï¼7.5%ï¼,respectively. Complications occurred in 65 patientsï¼31.4%ï¼, the most common complications were hoarseness caused by X-cranial nerve palsy. Conclusion:There are various pathological types of parapharyngeal space tumors, and surgery is the first choice for parapharyngeal space tumors. The surgical plan should be made according to the imaging examinations, lesions, and the pathology et al. The risk of complications should be fully informed before the operation, and the cooperation of the patients should be obtained.
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Neoplasias Faríngeas , Feminino , Humanos , Masculino , Espaço Parafaríngeo , Complicações Pós-Operatórias , Estudos Retrospectivos , Base do CrânioRESUMO
Objective:To analyze the causes of misdiagnosis of patients with glomus jugulare tumor. Method:The clinical data of 116 patients with glomus jugulare tumor were retrospectively analyzed. Result:Among the 116 patients, 65 were misdiagnosed, the average duration of misdiagnosis was 4.90 years. The misdiagnosed diseases were chronic otitis media or cholesteatoma in 25 cases, neurological tinnitus or hearing loss in 16 cases, facial paralysis in 6 cases, external auditory canal masses in 4 cases, secretory otitis media in 3 cases, neck mass in 3 cases, intracranial neoplasma in 2 cases, middle ear cancer in 1 case, vocal cord paralysis in 1 case, stomatitis in 1 case, optic nerve head edema in 1 case, middle ear hemangioma in 1 case and vascular tinnitus in 1 case. Conclusion:The misdiagnosis of glomus jugulare tumor can be summarized as follows: the patients' first symptoms were not specific; lack of auxiliary examination, especially imaging examination; physicians have insufficient understanding of imaging and pathological examination of glomus jugulare tumor.
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Paralisia Facial , Tumor do Glomo Jugular , Zumbido , Erros de Diagnóstico , Humanos , Estudos RetrospectivosRESUMO
The underlying mechanism involved in auditory neuropathy spectrum disorder (ANSD) remains largely unclear. It has been previously reported that mutations in the apoptosisinducing factor (AIF) gene are associated with auditory neuropathy and delayed peripheral neuropathy, which can eventually cause ANSD. In the present study, the regulatory effects of AIF knockdown on the cellular functions of spiral ganglion neurons (SNGs) and the molecular mechanism(s) of AIF knockdown in inducing cell apoptosis in SGNs were further investigated. The results showed that the AIF knockdown via siRNA transfection resulted in high levels of oxidative stress, and impaired mitochondrial respiration activity and membrane potential in SGNs. Western blotting further proved that the knockdown of AIF can decrease the content of antiapoptotic and antioxidative proteins, as well as mitochondrial respiratory chain Complex I proteins. The present experimental data suggested that the abnormal expression of AIF may affect SGNs cellular function, and may contribute to the progress of ANSD.
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Fator de Indução de Apoptose/metabolismo , Apoptose , Cóclea/metabolismo , Técnicas de Silenciamento de Genes , Mitocôndrias/metabolismo , Neurônios/metabolismo , Gânglio Espiral da Cóclea/metabolismo , Trifosfato de Adenosina/biossíntese , Animais , Respiração Celular , Células Cultivadas , Neurônios/patologia , Oxirredução , Estresse Oxidativo , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos Sprague-Dawley , Gânglio Espiral da Cóclea/patologiaRESUMO
BACKGROUND: The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei Province are less understood. METHODS: We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen City, China, from January 11, 2020, to February 6, 2020, and followed until March 6, 2020. RESULTS: Among the 298 confirmed cases, 233 (81.5%) had been to Hubei, while 42 (14%) did not have a clear travel history. Only 218 (73.15%) cases had a fever as the initial symptom. Compared with the nonsevere cases, severe cases were associated with older age, those with underlying diseases, and higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS: In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild, and there are sufficient medical resources to care and treat the disease.
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Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Fatores Etários , Antivirais/uso terapêutico , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Feminino , Hospitalização , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
ABSTRACT Purpose Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic significance of the preoperative serum TC levels for patients with surgically treated RCC. Material and Methods The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance by using random-effects models. Results Nine cohort studies comprising 15.609 patients were identified. Low preoperative serum TC levels were associated with poor cancer-specific survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no significant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. Conclusions Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.
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Humanos , Carcinoma de Células Renais/sangue , Colesterol/sangue , Neoplasias Renais/sangue , Prognóstico , Carcinoma de Células Renais/cirurgia , Biomarcadores Tumorais/sangue , Análise de Sobrevida , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Observacionais como Assunto , Período Pré-Operatório , Neoplasias Renais/cirurgiaAssuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic signifi cance of the preoperative serum TC levels for patients with surgically treated RCC. MATERIAL AND METHODS: The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confi dence intervals (CIs) were calculated through inverse variance by using random effects models. RESULTS: Nine cohort studies comprising 15.609 patients were identifi ed. Low preopera- tive serum TC levels were associated with poor cancer-specifi c survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no signifi cant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. CONCLUSIONS: Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.
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Carcinoma de Células Renais/sangue , Colesterol/sangue , Neoplasias Renais/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Estudos Observacionais como Assunto , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Reprodutibilidade dos Testes , Análise de SobrevidaRESUMO
BACKGROUND: The molecular and genetic research showed the association between DFNA11 and mutations in MYO7A. This research aimed to identify a MYO7A mutation in a family with nonsyndromic autosomal dominant hearing loss. METHODS: We have ascertained one large multigenerational Chinese family (Z029) with autosomal dominant late-onset progressive non-syndromic sensorineural hearing loss. Genome-wide linkage analysis of the family mapped the disease locus to the DFNA11 interval, where the MYO7A was considered as a candidate gene. Sequencing of the PCR products was carried out for each sample. One hundred and fifty one control subjects with normal hearing functions were also evaluated. RESULTS: The pathogenic mutation (c.2011G>A) was identified in the family. This mutation co-segregated with hearing loss in this family. No mutation of MYO7A gene was found in the 151 controls. CONCLUSIONS: The missense mutation of MYO7A is identified in the family displaying the pedigree consistent with DFNA11. We not only examined the clinical and genetic characteristics of the family, but also provided a basis for genetic counseling. We also summarized and analyzed the phenotypes and genotypes of all DFNA11 families, four of nine are Chinese families, suggesting that MYO7A mutations are not rare. Therefore, we should pay more attention to Chinese patients.
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Perda Auditiva Neurossensorial/genética , Miosinas/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Miosina VIIa , Fenótipo , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to explore the pathway cross-talks and key pathways in non-small cell lung cancer (NSCLC) to better understand the underlying pathological mechanism. METHODS: Integrated gene expression data, pathway data and protein-protein interaction (PPI) data were assessed to identify the pathway regulatory interactions in NSCLC, and constructed the background and disease pathway crosstalk networks, respectively. In this work, the attractor method was implemented to identified the differential pathways, and the rank product (RP) algorithm was used to determine the importance of pathways. RESULTS: Based on 787,896 PPI interactions from STRING database and 300 human pathways from KEGG, we constructed the back pathway cross-talk network with 300 nodes and 42239 edges. Integrating with expression data of NSCLC, each pathway cross-talk endowed with a weight value, and disease pathway cross-talks were identified. By RP algorithm and topology analysis of network, we selected 5 key pathways, including Alanine, DNA replication, Fanconi anemia pathway, Cell cycle and MicroRNAs in cancer under the pre-set thresholds. CONCLUSION: We successfully revealed the disease pathway cross-talks and explored 5 key pathways in NSCLC, which may be the underlying therapeutic targets for lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Redes Reguladoras de Genes/genética , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologiaRESUMO
OBJECTIVE: To evaluate the therapeutic effects, larynx preservation and adverse events of non-surgical combined treatments for laryngeal organ preservation in locally advanced laryngeal squamous cell carcinomas(SCCs). METHODS: Forty-six patients with locally advanced laryngeal carcinoma (T2-4, N0-N3) were treated individually with non-surgical combined treatments for larynx preservation (LP). These treatments included concurrent chemoradiotherapy (CCRT)(±epidermal growth factor receptor (EGFR) inhibitor), induction chemotherapy (ICT) followed by CCRT(± EGFR inhibitor), or concurrent radiotherapy and EGFR inhibitor. Radiation therapy was given to a total dose of 60-70 Gy. The Kaplan-Meier method was used to determine the overall survival. Side-effects were evaluated with the established Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. RESULTS: The average follow-up time was 31.8 months (range 6-95 months). All patients completed the planned radiotherapy without treatment breaks, and 45(97.8%) of 46 patients completed the planned chemotherapy.The 3-year and 5-year overall survival rates were 87.3%and 67.2%, respectively.The 5-year larynx preservation rate was 100.0%. The 3-year and 5-year progression free survival rates were 95.1% and 87.7%, respectively. The most common acute side effect in grade 3 was oropharyngeal mucositis. After treatment, tracheotomy was still required in 2 patients with glottis cancer for laryngeal edema or stenosis. No patient depended on a percutaneous gastrostomy and experienced speech impairment. CONCLUSION: Patients with locally advanced laryngeal cancer can be offered non-surgical combined treatments for laryngeal preservation and the high quality of life, showing a higher laryngeal preservation survival rate with minimal toxicities.