Genetic association study of TERT gene variants with chronic kidney disease susceptibility in the Chinese population.

The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the progression of CKD. Telomerase reverse transcriptase (TERT) may be implicated in the development of CKD. This study aimed to investigate the correlation between TERT gene variants and susceptibility to CKD in the Chinese population. A total of 507 patients with CKD and 510 healthy controls were recruited for this case-control study. Four candidate loci were identified using the MassARRAY platform. Logistic regression analysis was employed to assess the association between TERT gene variants and the risk of CKD. The false positive reporting probability (FPRP) method was utilized to evaluate the validity of statistically significant associations. The multifactorial dimensionality reduction (MDR) method was used to evaluate the interaction between SNPs and the risk of CKD. Furthermore, discrepancies in the clinical features of subjects with diverse genotypes were evaluated using one-way analysis of variance (ANOVA). Our findings revealed a correlation between rs2735940 and rs4635969 and an increased risk of CKD. Stratification analysis indicated that rs4635969 was related to an increased risk of CKD in different subgroups (age ≤ 50 years and male). MDR analysis indicated that the two-site model (rs2735940 and rs4635969) was the best prediction model. Furthermore, the rs2735940 GG genotype was found to be linked to an increased level of microalbuminuria (MAU) in patients with CKD. Our study is the first to reveal a connection between TERT gene variants and susceptibility to CKD, providing new insights into the field of nephrology.

Association of glycemic variability with death and severe consciousness disturbance among critically ill patients with cerebrovascular disease: analysis of the MIMIC-IV database.

BACKGROUND: The association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death. METHOD: We extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves. RESULTS: The present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality. CONCLUSION: High glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.

The mutation features and geographical distributions of the surface glycoprotein (S gene) in SARS-CoV-2 strains: A comparative analysis of the early and current strains.

The surface glycoprotein (S protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to develop coronavirus disease 2019 (COVID-19) vaccines. However, SARS-CoV-2, especially the S protein, has undergone rapid evolution and mutation, which has remained to be determined. Here, we analyzed and compared the early (12 237) and the current (more than 10 million) SARS-CoV-2 strains to identify the mutation features and geographical distribution of the S gene and S protein. Results showed that in the early strains, most of the loci were with relative low mutation frequency except S: 23403 (4486 strains), while in the current strains, there was a surge in the mutation strains and frequency, with S: 23403 constantly being the highest one, but tremendously increased to approximately 1050 times. Furthermore, D614 (S: 23403) was one of the most highly frequent mutations in the S protein of Omicron as of March 2022, and most of the mutant strains were still from the United States, and the United Kingdom. Further analysis demonstrated that in the receptor-binding domain, most of the loci with low mutation frequency in the early strains, while S: 22995 was nowadays the most prevalent loci with 3 122 491 strains in the current strains. Overall, we compare the mutation features of the S region in SARS-CoV-2 strains between the early and the current stains, providing insight into further studies in concert with emerging SARS-CoV-2 variants for COVID-19 vaccines.

Prediction of Patient Survival with Psoas Muscle Density Following Transjugular Intrahepatic Portosystemic Shunts: A Retrospective Cohort Study.

BACKGROUND Psoas muscle density (PMD) as a nutritional indicator is a tool to evaluate sarcopenia, which is commonly diagnosed in patients with liver cirrhosis. However, there are limited data on its role in patients who have received a transjugular intrahepatic portosystemic shunt (TIPS). We aimed to determine the utility of PMD in predicting mortality of patients with TIPS implantation and to compare the clinical value of PMD, Child-Pugh score, model for end-stage liver disease (MELD) score, and MELD paired with serum sodium measurement (MELD-Na) score in predicting post-TIPS survival in 1 year. MATERIAL AND METHODS This retrospective study included 273 patients who met the criteria for study inclusion. All participants underwent computed tomography (CT) scans, Child-Pugh score evaluation, MELD-Na scoring, and MELD scoring. Post-TIPS survival time was estimated using the Kaplan-Meier survival curve. The prognostic values of scoring models such as the Child-Pugh score, MELD, MELD-Na, and PMD were evaluated using receiver operating characteristic curves. RESULTS During the 1-year follow-up period, 31 of 273 (11.36%) post-TIPS patients died. Multivariate analysis identified PMD as an independent protective factor. PMD showed a good ability to predict the occurrence of an endpoint within 1 year after TIPS. The area under the receiver operating characteristic curves for PMD, Child-Pugh score, MELD score, and MELD-Na for predicting mortality were, respectively, 0.72 (95% confidence interval [CI]: 0.663-0.773), 0.59 (95% CI: 0.531-0.651), 0.60 (95% CI: 0.535-0.655), and 0.58 (95% CI: 0.487-0.608). CONCLUSIONS PMD has appreciable clinical value for predicting the mortality of patients with TIPS implantation. In addition, PMD is superior to established scoring systems for identifying high-risk patients with a poor prognosis.

Data Mining the Prognostic Biomarkers: miRNAs Targeting the Chemotherapeutic Agent 5-Fluorouracil in Colon Cancer.

BACKGROUND: Colon cancer is one of the most common and has the highest mortality rate in the world. MicroRNAs (miRNAs) as potential biomarkers play crucial roles in diagnosis, prognosis, and drug-response prediction of colon cancer. METHODS: In this study, we collected miRNA expression data from the Broad GDAC Firehose and screened specific miRNA-gene pairs after treatment with 5-fluorouracil treatment and used COAD analysis to study the association of miRNAs and inhibitor of the inhibitory genes. Potential drug-related miRNAs were further extracted via hypergeometric testing. RESULTS: The results showed that 13,651 miRNA-gene pairs were retrieved, including 242 miRNAs and 5,179 genes. The association between miRNAs and the inhibitor of inhibitory genes DPYD, TYMS, UNG was indicated. We further extracted 4 potential drug-related miRNAs, including hsa-mir-551a, hsa-mir-144, hsa-mir-519b, hsa-mir-506. The miRNA-gene pairs associated with 5-fluorouracil exhibit better prognosis in patients with CRC. CONCLUSIONS: We expected that up-regulation of hsa-mir-551a, hsa-mir-144, and hsa-mir-506 and down-regulation of hsa-mir-519b would exhibit better prognosis. The findings would underpin the fundamental hypothesis of mi-RNAs being prognostic signal biomarkers in therapy of 5-fluorouracil in CRC.

Prognostic Value of Acute-On-Chronic Liver Failure (ACLF) Score in Critically Ill Patients with Cirrhosis and ACLF.

BACKGROUND In the intensive care unit (ICU), critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF) continue to have high mortality rates. The AARC ACLF score is a simple, newly-developed score based on Asian ACLF patients, which performs well in prognosis. The present study attempted to verify the prognostic ability of AARC ACLF in non-Asian critically ill patients with cirrhosis and ACLF. MATERIAL AND METHODS We enrolled 786 patients. Relevant clinical data were collected within 24 h after admission to compare the differences between survivors and non-survivors, and all the patients were followed up for at least 180 days. RESULTS The 28-day, 90-day, and 180-day mortality rates were 28.9% (227/786), 36.4% (286/786), and 40.3% (317/786), respectively. Multivariate Cox regression analysis showed that AARC ACLF score (HR: 1.375, 95% CI: 1.247-1.516, P<0.001) was an independent predictive factor of 28-day mortality, and the AUROC of the predictive ability in 28-day mortality of the AARC ACLF score was 0.754. In addition, the AARC ACLF score was regraded into 3 classes (low risk: AARC ACLF <9, intermediate risk: 9≤ AARC ACLF <12, and high risk: AARC ACLF ≥12). The AARC ACLF score can be used for dynamic assessment by retest at days 4-7. CONCLUSIONS The AARC ACLF score has a good predictive value for 28-day, 90-day, and 180-day mortality in non-Asian critically ill patients with cirrhosis and ACLF, which is not inferior to CLIF-C ACLFsLact and other models. It is easy to use at bedside, and it is dynamic and reliable.

Risk Factors and Prediction of 28-Day-All Cause Mortality Among Critically Ill Patients with Acute Pancreatitis Using Machine Learning Techniques: A Retrospective Analysis of Multi-Institutions.

Objective: This study aimed to identify the risk factors and construct a reliable prediction model of 28-day all-cause mortality in critically ill patients with acute pancreatitis (AP) using machine learning techniques. Methods: A total of 534 patients from three different institutions were included. Thirty-eight possible variables were collected from the Intensive care unit (ICU) admission for investigation. Patients were split into a training cohort (n = 400) and test cohort (n = 134) according to their source of hospital. The synthetic minority oversampling technique (SMOTE) was introduced to handle the inherent class imbalance. Six machine learning algorithms were applied in this study. The optimal machine learning model was chosen after patients in the test cohort were selected to validate the models. SHapley Additive exPlanation (SHAP) analysis was performed to rank the importance of variable. The predictive performance of the models was evaluated by the calibration curve, area under the receiver operating characteristics curves (AUROC), and decision clinical analysis. Results: About 13.5% (72/534) of all patients eventually died of all-cause within 28 days of ICU admission. Eight important variables were screened out, including white blood cell count, platelets, body temperature, age, blood urea nitrogen, red blood cell distribution width, SpO2, and hemoglobin. The support vector machine (SVM) algorithm performed best in predicting 28-d all-cause death. Its AUROC reached 0.877 (95% CI: 0.809 to 0.927, p < 0.001), the Youden index was 0.634 (95% CI: 0.459 to 0.717). Based on the risk stratification system, the difference between the high-risk and low-risk groups was significantly different. Conclusion: In conclusion, this study developed and validated SVM model, which better predicted 28-d all-cause mortality in critically ill patients with AP. In the future, we will continue to include patients from more institutions to conduct validation in different contexts and countries.

A nomogram for predicting prognosis in patients with transjugular intrahepatic portosystemic shunt creation based on deep learning-derived spleen volume-to-platelet ratio.

OBJECTIVES: The objective of our study was to develop a nomogram to predict post-transjugular intrahepatic portosystemic shunt (TIPS) survival in patients with cirrhosis based on CT images. METHODS: This retrospective cohort study included patients who had received TIPS operation at the Wenzhou Medical University First Affiliated Hospital between November 2013 and April 2017. To predict prognosis, a nomogram and Web-based probability were developed to assess the overall survival (OS) rates at 1, 3, and 5 years based on multivariate analyses. With deep learning algorithm, the automated measurement of liver and spleen volumes can be realized. We assessed the predictive accuracy and discriminative ability of the nomogram using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Age, total bilirubin, and spleen volume-to-platelet ratio (SVPR) were identified as the independent risk factors for OS. The nomogram was constructed based on the above risk factors. The C-index (0.80, 0.74, 0.70), ROC curve (area under curve: 0.828, 0.761, 0.729), calibration curve, and DCA showed that nomogram good at predictive value, stability, and clinical benefit in the prediction of 1-, 3-, 5-year OS in patients with TIPS creation. CONCLUSIONS: We constructed a nomogram for predicting prognosis in patients with TIPS creation based on risk factors. The nomogram can help clinicians in identifying patients with poor prognosis, eventually facilitating earlier treatment and selecting suitable patients before TIPS. ADVANCES IN KNOWLEDGE: This study developed the first nomogram based on SVPR to predict the prognosis of patients treated with TIPS. The nomogram could help clinician in non-invasive decision-making.

Predicting ICU Interventions: A Transparent Decision Support Model Based on Multivariate Time Series Graph Convolutional Neural Network.

In this study, we present a novel approach for predicting interventions for patients in the intensive care unit using a multivariate time series graph convolutional neural network. Our method addresses two critical challenges: the need for timely and accurate decisions based on changing physiological signals, drug administration information, and static characteristics; and the need for interpretability in the decision-making process. Drawing on real-world ICU records from the MIMIC-III dataset, we demonstrate that our approach significantly improves upon existing machine learning and deep learning methods for predicting two targeted interventions, mechanical ventilation and vasopressors. Our model achieved an accuracy improvement from 81.6% to 91.9% and a F1 score improvement from 0.524 to 0.606 for predicting mechanical ventilation interventions. For predicting vasopressor interventions, our model achieved an accuracy improvement from 76.3% to 82.7% and a F1 score improvement from 0.509 to 0.619. We also assessed the interpretability by performing an adjacency matrix importance analysis, which revealed that our model uses clinically meaningful and appropriate features for prediction. This critical aspect can help clinicians gain insights into the underlying mechanisms of interventions, allowing them to make more informed and precise clinical decisions. Overall, our study represents a significant step forward in the development of decision support systems for ICU patient care, providing a powerful tool for improving clinical outcomes and enhancing patient safety.

Vitamin C inhibits NLRP3 inflammasome activation and delays the development of age-related hearing loss in male C57BL/6 mice.

The efficacy of vitamin C in age-related hearing loss, i.e., presbycusis, remains debatable. On a separate note, inflammation induced by the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is involved in the progression of presbycusis. In this study, we investigated the effect of vitamin C on male C57BL/6 mice's presbycusis and NLRP3 inflammasome. The results showed that vitamin C treatment improved hearing, reduced the production of inflammatory factors, inhibited NLRP3 inflammasome activation, and decreased cytosolic mitochondrial DNA (mtDNA) in the C57BL/6 mouse cochlea, inferior colliculus, and auditory cortex. According to this study, vitamin C protects auditory function in male C57BL/6 presbycusis mice through reducing mtDNA release, inhibiting the NLRP3 inflammasome activation in the auditory pathway. Our study provides a theoretical basis for applying vitamin C to treat presbycusis.

Prediction of Patient Hepatic Encephalopathy Risk with Freiburg Index of Post-TIPS Survival Score Following Transjugular Intrahepatic Portosystemic Shunts: A Retrospective Study.

Background: Hepatic encephalopathy is a complication of portal hypertension. The Freiburg index of transjugular portosystemic shunt (TIPS) and patient outcomes have recently been described. This retrospective study was conducted at a single center in China and included 241 patients with portal hypertension who underwent TIPS implantation to evaluate the Freiburg index of post-TIPS survival score (FIPS) to predict hepatic encephalopathy. Methods: A single-center retrospective study including 241 patients who underwent TIPS operation between April 2015 and July 2019 was conducted. Clinical demographics and relevant clinical parameters within 24h after admission were collected. The prediction performances of FIPS, Child-Pugh and the model for end-stage liver disease (MELD) scores were compared by decision curve analysis and receiver operating characteristic (ROC) curve analysis. In addition, multivariate analyses were performed to identify independent predictors. Results: Eighty-three out of 241 patients (34.4%) finally developed post-TIPS hepatic encephalopathy. The area under the ROC curve of FIPS was 0.744 (95% confidence interval: 0.684-0.798). FIPS was identified as an independent risk factor for post-TIPS hepatic encephalopathy (hazard ratio: 2.23, 95% confidence interval: 1.71-2.90, p<0.001). Moreover, we further grouped the FIPS scores into two categories (FIPS ≤-0.97, low-risk; FIPS >-0.97, high risk) to improve its applicability. Patients with high FIPS scores had a significantly higher incidence of hepatic encephalopathy than patients with low FIPS scores (P<0.05). Conclusion: This study showed that FIPS could be used to evaluate the risk of hepatic encephalopathy in this patient group with improved predictive performance when compared with the Child-Pugh and MELD scores.

Psoas Muscle Density Predicts Occurrences of Hepatic Encephalopathy in Patients Receiving Transjugular Intrahepatic Portosystemic Shunts within 1 year.

PURPOSE: We aimed to assess the efficacy of psoas density (PD) for predicting hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) procedures. METHODS: Data were collected from patients who underwent TIPS procedures at a single institution between 2013 and 2019. PD was manually measured using software on unenhanced CT scans at the level of third lumbar vertebra. Laboratory and physical examination data were collected within 24 h after admission in order to compare the differences between patients with and without post-TIPS HE. RESULTS: A total of 251 patients were included in this study. Among these patients, 77 (30.7%) developed post-TIPS HE within one year after TIPS creation. The threshold of PD for predicting HE was 51.24 Hounsfield unit (HU). PD values less than this threshold were correlated with an increased risk of HE (hazard ratio 0.92; 95% CI 0.89-0.95, P < 0.001). The area under the receiver operating characteristic curve (AUROC) of PD was 0.743 (95% CI 0.685-0.796), which was superior to Model for End-stage Liver Disease (MELD) (0.569, P = 0.007), albumin-bilirubin score (ALBI) (0.641, P = 0.018), and Child-Pugh score (0.583, P = 0.003). CONCLUSION: PD measurement showed good HE predictive value in cirrhotic patients who underwent TIPS. This measure also performed better than MELD, ALBI and Child-Pugh.

Clinical Outcome of Day-3 Cleavage Slow-Growing Embryos at Different Cleavage Rates after Overnight Culture: A Cohort Retrospective Study.

INTRODUCTION: We explored the association between clinical outcomes and the cleavage rate of day-3 cleavage slow-growing embryos after overnight culture. METHODS: The data collected from 303 frozen embryo transfer (FET) cycles with 606 4-cell or 5-cell embryos cultured overnight (18-22 h) after thawing were analyzed. Based on the growth rate after the overnight culture, the embryos were divided into three groups: no embryo reaching eight cells (Group I), either one of the two embryos reaching eight cells (Group II), and both two embryos reaching eight cells or more (Group III). A statistical analysis of the different clinical outcomes from the three groups was performed. RESULTS: Biochemical pregnancy rate (OR 3.22; p = 0.001), implantation rate (OR 2.44; p = 0.002), clinical pregnancy rate (OR 3.04; p = 0.001), ongoing pregnancy rate (OR 3.14; p = 0.001), and live birth rate (OR 2.78; p = 0.004) were significantly higher in Group III as compared to Group I. Group II had a significantly higher biochemical pregnancy rate (OR 2.02; p = 0.013) and implantation rate (OR 1.77; p = 0.019) than Group I. CONCLUSIONS: The capability of day-3 cleavage slow-growing embryos to reach eight cells, especially that of two embryos reaching eight cells by overnight culture, appear to result in a better pregnancy outcome.

Efficacy of albumin-bilirubin score to predict hepatic encephalopathy in patients underwent transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: The occurrence of hepatic encephalopathy is one of the main factors limiting the development and application of transjugular intrahepatic portosystemic shunt (TIPS). Our study aimed to verify the efficacy of the albumin-bilirubin score, an objective and simple scoring system, to predict post-TIPS hepatic encephalopathy. METHODS: From February 2014 to July 2019, a total of 224 patients who underwent TIPS procedure were entered into the study. All patients were followed up after TIPS placement. Relevant clinical data within 24 h after admission were collected to compare the differences between patients with and without hepatic encephalopathy after TIPS placement. RESULTS: A total of 82 (36.6%) patients developed post-TIPS hepatic encephalopathy. Age and albumin-bilirubin score was found to be independent risk factors for post-TIPS hepatic encephalopathy. The albumin-bilirubin score shows a good ability to predict the occurrence of hepatic encephalopathy within 1 year after TIPS. The area under the receiver operating characteristic curve is 0.74 (95% confidence interval: 0.673-0.806). In addition, in order to improve its feasibility, we regrouped the albumin-bilirubin score into three levels (albumin-bilirubin≤ -1.95, low risk; 1.95 -1.45, high risk). CONCLUSION: The albumin-bilirubin score has a good predictive value for the possibility of post-TIPS hepatic encephalopathy, which is better than the model for end-stage liver disease and Child-Pugh score.

Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome.

Background: rs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined. Methods: Three-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns. Results: Generally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice. Conclusion: Overall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma.

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC (P=0.040) and HNSCC (P=0.044), especially in HPV 16 integrated CC (P=0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC (P=0.013) and HNSCC (P=0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC (P=1.76e-67) and HNSCC (P<10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status (P<10e-10), higher mutation count (P<10e-10), higher fraction genome altered value (P=2.078e-4), higher aneuploidy score (P=3.362e-4), and earlier started the smoking year (P=2.572e-4), which were associated with shorter overall survival (P=0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC.

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis.

BACKGROUND: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. METHODS: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. RESULTS: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. CONCLUSIONS: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.

Independent effect of alanine transaminase on the incidence of type 2 diabetes mellitus, stratified by age and gender: A secondary analysis based on a large cohort study in China.

BACKGROUND: Previous studies have revealed that alanine aminotransferase (ALT) may be one of the risk factors of developing diabetes. We aimed to demonstrate the independent effect of ALT on incident diabetes and to investigate whether the association between ALT and incident diabetes is modified by age and gender in the general Chinese population. METHODS: The present study was a retrospective cohort study, including 210,051 Chinese adult participants. The primary outcome was developing diabetes. The serum ALT activities were stratified by quintiles. We obtained data from 'DATADRYAD' website and used the data for secondary analysis. RESULTS: At a median follow-up of 3.0 y, 4144 of 210,051 (1.97%) participants developed diabetes. After adjustment for potential confounders, a significantly higher risk of the incident diabetes (HR: 1.43, 95% CI: 1.25-1.63) was found in participants in the fifth quintile (Q5, ≥31 U/L) compared to those in the first to fourth quintiles (Q1-4) for ALT activities. Among males aged 30 to 40 and 40 to 50 y with the fifth quintile of ALT activity had 2.4- and 1.5-fold increased odds of developing diabetes, respectively, in comparison with those in the lower ALT activities. Among females with age 30 to 40 and ≥ 70 y, the fifth quintile of ALT activity had 4.9- and 2.2-fold increased odds for incident diabetes. CONCLUSION: Our result indicated that the ALT activity was positively associated with the incident diabetes among Chinese persons. Moreover, 30-40 y individuals, whether male or female, with elevated ALT activities had the greatest increased risk for diabetes compared with persons with lower ALT activities in the same age group.

[The research of intensity focused ultrasound on the treatment of allergic rhinitis].

Allergic rhinitis is a common disease in otorhinolaryngology, there are lots of physiotherapies now, the overview of the research of intensity focused ultrasound on the treatment of allergic rhinitis was mainly reviewed.

[Detection and correlation of lipopolysaccharide, vitamin D receptor and matrix metalloproteinase-9 in the middle ear cholesteatoma].

OBJECTIVE: To investigate the expression and concentration of lipopolysaccharide (LPS) and matrix metalloproteinase-9 (MMP-9) in middle ear cholesteatoma and discuss their relations. METHOD: Twenty-nine cases of middle ear cholesteatoma tissue, 18 cases of external auditory canal tissue were detected by limulus amebocyte lysate assay (LAL-assay), and expression of MMP-9 protein in formalin-fixed, paraffin-embedded tissues was detected by immunohistochemical method. RESULT: The concentrations of LPS in cholesteatoma were higher than that in external auditory canal tissues. In group of cholesteatoma: M = 0.739 0, IQR = 0.6203, and in group of external auditory canal tissues: M = -0.2538, IQR = 1.1692 (P < 0.01). In cholesteatoma groups, in extensive type: M = 0.8403, IQR = 0.5254; in localized type: M = 0.4048, IQR = 0.6139, the concentrations of LPS were higher in extensive cholesteatoma in comparison with localized cholesteatoma (P < 00.05). In cholesteatoma epithelium samples, MMP-9 were 79.3%. Compared with external auditory canal epithelium, the expression of MMP-9 was higher in middle ear cholesteatoma epithelium (P < 0.05). There was no significant difference in the expression of MMP-9 between two types of cholesteatoma epithelium (P > 0.05). LPS, MMP-9 weren't significantly correlated by Spearman test. CONCLUSION: LPS was responsible for middle ear cholesteatoma and its related bone erosion. MMP-9 was related to the development of middle ear cholesteatoma. There's no correlation between LPS and MMP-9.