Identification and quantification of immune infiltration landscape on therapy and prognosis in left- and right-sided colon cancer.

BACKGROUND: The left-sided and right-sided colon cancer (LCCs and RCCs, respectively) have unique molecular features and clinical heterogeneity. This study aimed to identify the characteristics of immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. METHODS: The independent gene datasets, corresponding somatic mutation and clinical information were collected from The Cancer Genome Atlas and Gene Expression Omnibus. The ICI contents were evaluated by "ESTIMATE" and "CIBERSORT." We performed two computational algorithms to identify the ICI landscape related to prognosis and found the unique infiltration characteristics. Next, principal component analysis was conducted to construct ICI score based on three ICI patterns. We analyzed the correlation between ICI score and tumor mutation burden (TMB), and stratified patients into prognostic-related high- and low- ICI score groups (HSG and LSG, respectively). The role of ICI scores in the prediction of therapeutic benefits was investigated by "pRRophetic" and verified by Immunophenoscores (IPS) (TCIA database) and an independent immunotherapy cohort (IMvigor210). The key genes were preliminary screened by weighted gene co-expression network analysis based on ICI scores. And they were further identified at various levels, including single cell, protein and immunotherapy response. The predictive ability of ICI score for prognosis was also verified in IMvigor210 cohort. RESULTS: The ICI features with a better prognosis were marked by high plasma cells, dendritic cells and mast cells, low memory CD4+ T cells, M0 macrophages, M1 macrophages, as well as M2 macrophages. A high ICI score was characterized by an increased TMB and genomic instability related signaling pathways. The prognosis, sensitivities of targeted inhibitors and immunotherapy, IPS and expression of immune checkpoints were significantly different in HSG and LSG. The genes identified by ICI scores and various levels included CA2 and TSPAN1. CONCLUSION: The identification of ICI subtypes and ICI scores will help gain insights into the heterogeneity in LCC and RCC, and identify patients probably benefiting from treatments. ICI scores and the key genes could serve as an effective biomarker to predict prognosis and the sensitivity of immunotherapy.

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/ß-catenin signaling.

BACKGROUND: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC. METHODS: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells. RESULTS: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/ß-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/ß-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p. CONCLUSIONS: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/ß-catenin signaling.

Proteins differentially expressed during limonene biotransformation by Penicillium digitatum DSM 62840 were examined using iTRAQ labeling coupled with 2D-LC-MS/MS.

This study focused on the differences in protein expression at various periods during limonene biotransformation by Penicillium digitatum DSM 62840. A total of 3644 protein-species were quantified by iTRAQ during limonene biotransformation (0 and 12 h). A total of 643 proteins were differentially expressed, 316 proteins were significantly up-regulated and 327 proteins were markedly down-regulated. GO, COG, and pathway enrichment analysis showed that the differentially expressed proteins possessed catalytic and binding functions and were involved in a variety of cellular and metabolic process. Furthermore, the enzymes involved in limonene transformation might be related to cytochrome P-450. This study provided a powerful platform for further exploration of biotransformation, and the identified proteins provided insight into the mechanism of limonene transformation.

Effect of Food Emulsifiers on Aroma Release.

This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release.

Expression and clinicopathological significance of Mel-18 mRNA in colorectal cancer.

Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in colorectal cancer (CRC) patients. For this purpose, expression of Mel-18 mRNA was evaluated in 82 primary CRC and paired noncancerous mucosa samples by qRT-PCR and Western blotting. We found that overall Mel-18 mRNA expression in the CRC tissue was significantly lower than in the noncancerous mucosal tissue (p = 0.007, Wilcoxon matched-pairs signed-ranks test). Mel-18 was conversely correlated with the pathological classifications (p = 0.003 for T, p < 0.001 for N, and p = 0.015 for M classifications, respectively) and clinical AJCC stage (p < 0.001). Furthermore, CRC patients with a higher level of Mel-18 showed prolonged disease-free survivals (DFS) (p < 0.001). In multivariate analysis, the diminished Mel-18 expression may be a risk factor for the patients' 3-year DFS (HR = 1.895; 95 % CI 1.032, 3.477; p = 0.039). It was therefore concluded that the lower Mel-18 expression might contribute to the CRC development/progression.

Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy.

BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan-Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement. RESULTS: The Cox proportional hazards regression showed pN as significantly associated with disease-specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables. CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model.

Sensitive determination of polychlorinated biphenyls in environmental water samples by headspace solid-phase microextraction with bamboo charcoal@iron oxide black fibers prior to gas chromatography with tandem mass spectrometry.

We have investigated the feasibility of bamboo charcoal@iron oxide black for the headspace solid-phase microextraction of polychlorinated biphenyls in environmental water samples. Bamboo charcoal@iron oxide black was prepared and used as a solid-phase microextraction coating material, and gas chromatography with tandem mass spectrometry was used for detection. Several important factors affecting the extraction efficiency were systematically investigated and optimized. Under the optimum conditions, the experimental data exhibited wide linear range over the range 0.2-1000 ng/L and low limits of detection in the range of 4.7-22.2 pg/L. The novel coating was successfully used for the enrichment and determination of polychlorinated biphenyls in real environmental water samples. All these results indicated that bamboo charcoal@iron oxide black-based headspace solid-phase microextraction coupled to gas chromatography with tandem mass spectrometry was an excellent alternative for the sensitive analysis of polychlorinated biphenyls at ultratrace levels in the environment.

Genistein induces G2/M arrest in gastric cancer cells by increasing the tumor suppressor PTEN expression.

Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN.

Bamboo charcoal as a novel solid-phase microextraction coating material for enrichment and determination of eleven phthalate esters in environmental water samples.

This study demonstrates the potential of bamboo charcoal as a novel and inexpensive solid-phase microextraction (SPME) coating material for enrichment and determination of organic pollutants in water samples. Bamboo charcoal was prepared and used as a SPME coating material. Eleven phthalate esters (PAEs) were used as model analytes, and gas chromatography-mass spectrometry was used for separation and detection. Important extraction conditions (ionic strength, stirring rate, and extraction time) and desorption conditions (desorption temperature and time) were systematically investigated and optimized. Linearity of 0.1-100 µg L(-1) and correlation coefficients of 0.9992-0.9998 were obtained under optimum conditions. Inter-day and intra-day repeatability were 2.15-9.93 % and 1.89-9.85 %, respectively, and fiber-to-fiber reproducibility was 5.42-9.66 %. On the basis of a chromatographic signal-to-baseline noise ratio of three, the limits of detection reached 0.004-0.023 µg L(-1). Satisfactory results were achieved when the bamboo coating was used for determination of 11 PAEs in real water samples. The experimental results indicate that bamboo charcoal has significant potential as a SPME coating material for rapid enrichment and sensitive determination of organic pollutants in environmental samples.

Will male semen quality improve with environmental quality?

Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30-35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.

Identification and initial validation of maximal tumor area as a novel prognostic factor for overall and disease-free survival in patients with resectable colon cancer: a retrospective study.

BACKGROUND: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer. METHODS: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P <0.05 was considered statistically significant. RESULTS: A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P <0.001; iAUC for DFS, 0.694, P <0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort. CONCLUSIONS: Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system.

Using Zn/Al layered double hydroxide as a novel solid-phase extraction adsorbent to extract polycyclic aromatic hydrocarbons at trace levels in water samples prior to the determination of gas chromatography-mass spectrometry.

This paper demonstrates, for the first time, the great potential of using Zn/Al layered double hydroxide intercalated sodium dodecyl benzene sulfonate (Zn/Al-SDBS-LDH) as a solid-phase extraction (SPE) material in the extraction of persistent organic pollutants prior to the determination of gas chromatography-mass spectrometry in environmental water samples. Zn/Al-SDBS-LDH, a relatively inexpensive and simply prepared material, was synthesized and used as a SPE adsorbent to quantitatively determine the concentration of five polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. Factors affecting extraction efficiency, such as, eluent type, eluent volume, flow rate of sample, sample volume, and amount of adsorbent, were investigated and optimized in detail. Experimental results indicate that there is an excellent linear relationship between peak area and the concentration of PAHs over the range of 5-500 ng L(-1), and the precisions (relative standard deviation (RSD)) were 2.5-6.3% under the optimum conditions. Based on the ratio of chromatographic signal-to-base line noise (S/N = 3), the limits of detection could reach 1.2-3.2 ng L(-1). This novel method was successfully applied to the analysis of PAHs in environmental water samples. As such, we show here that the use of Zn/Al-SDBS-LDH as SPE adsorbent materials, coupled with gas chromatography-mass spectrometry, is an excellent improvement in the routine analysis of PAHs at trace levels in the environment.

Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth.

PURPOSE: Increasing experimental evidences suggest that ubiquitin-specific protease 22 (USP22), a cancer stem cell marker, plays a crucial role in pathological processes of epithelial malignancies and other solid tumors, which makes it a potential target for cancer therapy. The aim of this study was to study the roles of USP22 in human colorectal cancer cell line HCT116 by suppressing USP22 expression with micro-interfering RNA (miRNA). METHODS: With the knock-down of USP22, the changes of cellular proliferation, cell cycle, cell apoptosis, and major vault protein (MVP) expression were investigated. Furthermore, a tumor xenograft model in nude mice was injected with USP22 miRNA silencing vector and the immunohistochemical staining was performed to evaluate the USP22 expression in the tumor. RESULTS: The knock-down of USP22 protein expression by miRNA resulted in the inhibition of cellular proliferation, the accumulation of cells in the G1 phase, the reduction of apoptosis, and the down-regulation of MVP expression. Furthermore, with orthotopic mice as a model, tumor growth was suppressed when USP22 miRNA silencing vector was injected. Immunohistochemical analyses of tumor sections revealed that USP22 expression in animals decreased when USP22 expression was inhibited by miRNA. CONCLUSION: These results support the hypothesis that USP22 plays a crucial role in tumor formation and growth by regulating cell proliferation with USP22-dependent signaling pathway. Furthermore, USP22 acts as a major transcriptional factor to regulate MVP drug resistant gene. Taken together, targeting USP22 may offer additional possibilities in cancer therapy.

[Water Quality Assessment and Spatial-temporal Variation Analysis in Yellow River Basin].

During the implementation of ecological protection in the Yellow River basin, understanding the water pollution status and spatio-temporal variation of water quality has become the most important thing for water safety in the basin. To analyze the water quality in recent years, the water quality data in the Yellow River basin from 2004 to 2018 were firstly collected from eight typical monitoring stations. Using a combination of multivariate data analysis methods including the Mann-Kendall (M-K) trend test, hierarchical clustering analysis (HCA), principal component analysis (PCA), and modified comprehensive water quality identification index (WQI), the spatio-temporal variation characteristics of the water quality were then explored in the Yellow River basin. The results indicated that in terms of time variation, the HCA from the water quality time series showed that the water quality of the Yellow River basin could be divided into the wet season, normal season, and dry season, being basically consistent with the hydrological period. Combined with the M-K trend test and WQI-based water quality assessment, the water quality of the Yellow River basin was improving gradually, with 2010 as the critical year. The water quality in the wet season was superior to that in the dry season. The pollution indicator NH4+-N and permanganate index were dominant in both the wet season and dry season. According to the spatial variation analysis, the water quality for all the studied stations improved significantly. Spatial clustering showed that the S6 (Shanxi Yuncheng Hejin Bridge) was obviously different from others, and further comparative study demonstrated that S6 was constantly seriously polluted. The S7 (Henan Jiyuan Xiaolangdi) exhibited different characteristics in the wet and dry season. In all stations, NH4+-N was considered to be the most common pollution indicator, whereas the permanganate index and DO were also relatively serious for S6. In different hydrological seasons, NH4+-N and the permanganate index showed different characteristics, and their variety was related to the fact that the former mainly came from domestic and industrial sources, whereas the latter was mainly derived from agricultural sources. The modified WQI showed obvious advantages over single-factor water quality assessment, and the findings from this study can provide scientific evidence for water pollution control and comprehensive water quality management in the Yellow River basin.

Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration.

Introduction: This study aimed to identified the key genes and sequencing metrics for predicting prognosis and efficacy of neoadjuvant chemotherapy (nCT) in rectal cancer (RC) based on genomic DNA sequencing in samples with different origin and multi-omics association database. Methods: We collected 16 RC patients and obtained DNA sequencing data from cancer tissues and plasma cell-free DNA before and after nCT. Various gene variations were analyzed, including single nucleotide variants (SNV), copy number variation (CNV), tumor mutation burden (TMB), copy number instability (CNI) and mutant-allele tumor heterogeneity (MATH). We also identified genes by which CNV level can differentiate the response to nCT. The Cancer Genome Atlas database and the Clinical Proteomic Tumor Analysis Consortium database were used to further evaluate the specific role of therapeutic relevant genes and screen out the key genes in multi-omics levels. After the intersection of the screened genes from differential expression analysis, survival analysis and principal components analysis dimensionality reduction cluster analysis, the key genes were finally identified. Results: The genes CNV level of principal component genes in baseline blood and cancer tissues could significantly distinguish the two groups of patients. The CNV of HSP90AA1, EGFR, SRC, MTOR, etc. were relatively gained in the better group compared with the poor group in baseline blood. The CNI and TMB was significantly different between the two groups. The increased expression of HSP90AA1, EGFR, and SRC was associated with increased sensitivity to multiple chemotherapeutic drugs. The nCT predictive score obtained by therapeutic relevant genes could be a potential prognostic indicator, and the combination with TMB could further refine prognostic prediction for patients. After a series of analysis in multi-omics association database, EGFR and HSP90AA1 with significant differences in multiple aspects were identified as the key predictive genes related to prognosis and the sensitivity of nCT. Discussion: This work revealed that effective combined application and analysis in multi-omics data are critical to search for predictive biomarkers. The key genes EGFR and HSP90AA1 could serve as an effective biomarker to predict prognose and neoadjuvant chemosensitivity.

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer.

Background: This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively). Methods: We comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs. Results: Two ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses. Conclusion: This work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.

Hypnotics Use Is Associated with Elevated Incident Atrial Fibrillation: A Propensity-Score Matched Analysis of Cohort Study.

We aimed to investigate the association between either or both of benzodiazepines (BZDs) and non-BZDs and the incidence of atrial fibrillation (AF) in the Taiwan National Health Insurance Database. The participants with at least two prescriptions of BZDs and/or non-BZDs were identified as hypnotics users, whereas those without any prescription of hypnotics were non-hypnotics users. The hypnotics and non-hypnotics cohorts were 1:1 matched on their propensity scores. A total of 109,704 AF-free individuals were included; 610 AF cases occurred in the 54,852 hypnotics users and 166 in the 54,852 non-hypnotics users during the 602,470 person-years of follow-up, with a higher risk of new-onset AF in the users than the non-users (hazard ratio (HR): 3.61, 95% confidence interval [CI]: 3.04−4.28). The users at the highest tertiles of the estimated defined daily doses per one year (DDD) had a greater risk for AF than the non-users, with the risk increasing by 7.13-fold (95% CI: 5.86−8.67) for >0.74-DDD BZDs, 10.68-fold (95% CI: 6.13−18.62) for >4.72-DDD non-BZDs, and 3.26-fold (95% CI: 2.38−4.47) for > 1.65-DDD combinations of BZDs with non-BZDs, respectively. In conclusion, hypnotics use was associated with elevated incidence of AF in the Taiwanese population, which highlighted that the high-dose usage of hypnotics needs more caution in clinical cardiological practice.

Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer.

BACKGROUND: The present study was aimed at clarifying the expression of ubiquitin carboxyl-terminal hydrolase 22 (USP22), a novel deubiquitinating enzyme gene, in colorectal cancer (CRC) and its clinical significance. METHODS: USP22 expression was detected with quantitative RT-PCR, Western blot, and immunohistochemistry (IHC) in 43 CRCs and non-cancerous matched tissues. Furthermore, USP22 protein expression was analyzed in 192 CRC tumors by IHC to evaluate the association with survival. RESULTS: In 43 paired fresh tissues, the expression level of USP22 was significantly higher in primary CRCs than that in the paired non-cancerous tissues at both mRNA and protein levels (P < 0.0001). Nuclear USP22 expression significantly increased from normal mucosa through adenoma to primary carcinoma (P < 0.0001) and from primary carcinoma to liver metastasis (P = 0.021). The incidence of positive USP22 expression was 54.16% in 192 conventional CRC tissues. Notably, high USP22 expression was significantly associated with shorter disease-specific survival (P < 0.0001) and shorter disease-free survival (P < 0.0001). Cox regression analysis showed USP22 was an independent prognostic parameter for CRC patients. CONCLUSION: USP22 might be an independent predictive factor for CRC prognosis and aberrant expression of USP22 may play an essential role in colorectal carcinogenesis and liver metastasis.

Prognostic Immunity and Therapeutic Sensitivity Analyses Based on Differential Genomic Instability-Associated LncRNAs in Left- and Right-Sided Colon Adenocarcinoma.

Background: The purpose of our study was to develop a prognostic risk model based on differential genomic instability-associated (DGIA) long non-coding RNAs (lncRNAs) of left-sided and right-sided colon cancers (LCCs and RCCs); therefore, the prognostic key lncRNAs could be identified. Methods: We adopted two independent gene datasets, corresponding somatic mutation and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Identification of differential DGIA lncRNAs from LCCs and RCCs was conducted with the appliance of "Limma" analysis. Then, we screened out key lncRNAs based on univariate and multivariate Cox proportional hazard regression analysis. Meanwhile, DGIA lncRNAs related prognostic model (DRPM) was established. We employed the DRPM in the model group and internal verification group from TCGA for the purpose of risk grouping and accuracy verification of DRPM. We also verified the accuracy of key lncRNAs with GEO data. Finally, the differences of immune infiltration, functional pathways, and therapeutic sensitivities were analyzed within different risk groups. Results: A total of 123 DGIA lncRNAs were screened out by differential expression analysis. We obtained six DGIA lncRNAs by the construction of DRPM, including AC004009.1, AP003555.2, BOLA3-AS1, NKILA, LINC00543, and UCA1. After the risk grouping by these DGIA lncRNAs, we found the prognosis of the high-risk group (HRG) was significantly worse than that in the low-risk group (LRG) (all p < 0.05). In all TCGA samples and model group, the expression of CD8+ T cells in HRG was lower than that in LRG (all p < 0.05). The functional analysis indicated that there was significant upregulation with regard to pathways related to both genetic instability and immunity in LRG, including cytosolic DNA sensing pathway, response to double-strand RNA, RIG-Ⅰ like receptor signaling pathway, and Toll-like receptor signaling pathway. Finally, we analyzed the difference and significance of key DGIA lncRNAs and risk groups in multiple therapeutic sensitivities. Conclusion: Through the analysis of the DGIA lncRNAs between LCCs and RCCs, we identified six key DGIA lncRNAs. They can not only predict the prognostic risk of patients but also serve as biomarkers for evaluating the differences of genetic instability, immune infiltration, and therapeutic sensitivity.

Analysis of semen quality of 38 905 infertile male patients during 2008-2016 in Wenzhou, China.

This study analyzed the trend in semen quality of infertile male patients in Wenzhou, China, based on the data obtained from 38 905 patients during 2008-2016 in The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). The results showed that only 24.9% of the patients had normal semen quality. For the semen quality of infertile male patients, that of the workers and 40-year-olds was significantly worse than the other occupational and age groups. For all the infertile patients, low semen volume, asthenozoospermia, and teratozoospermia accounted for 8.4%, 50.5%, and 54.1%, respectively. During 2008-2016, the annual mean percentage of fast forward motile spermatozoa, percentage of total forward motile spermatozoa, and percentage of spermatozoa with normal morphology decreased linearly with slopes of -2.11, -2.59, and -0.70, respectively. The proportion of patients with asthenozoospermia and multi-abnormal spermatozoa increased during 2008-2016 with slopes of 4.70 and 4.87, respectively, while for low semen volume, it decreased with a slope of -0.47 in the same time period. The proportion of patients with teratozoospermia increased from 2008 to 2011 and from 2011 to 2016 with slopes of 17.10 and 2.09, respectively. In general, the deteriorating trend of semen quality of infertile male patients in Wenzhou was obvious. Future efforts should be made to reveal the adverse influences on semen quality, such as occupational exposure, environmental quality, and living habits. Furthermore, more pervasive reproduction health education is necessary.