Dexamethasone inhibits androgen receptor-negative prostate cancer cell proliferation via the GR-FOXO3a-GAS5 axis.

Background: Studies have shown that glucocorticoid receptor (GR) has inconsistent effects on the proliferation of prostate cancer cells, we found dexamethasone inhibited the proliferation of androgen receptor-negative prostate cancer cells, but the underlying mechanisms remain to be illustrated. Methods: GR expression and its prognosis role were analyzed based on the TCGA dataset. Bioinformatic analysis was performed to identify the candidate of GR downstream, which includes FOXO3a. After overexpressing FOXO3a in PC-3 cells, cell counting kit-8 (CCK-8) and migration assays were performed to evaluate cell proliferation and migration ability. Regulation of FOXO3a on GAS5 was also analyzed by JASPAR and PCR. Results: GR had low expression in prostate cancer and predicted poor prognosis. FOXO3a was identified as the downstream of GR to inhibit the proliferation of prostate cancer cells. Moreover, FOXO3a directly induces GAS5 expression, forming the GR-FOXO3a-GAS5 signaling pathway. Conclusion: Our study showed that GR played a role as a tumor suppressor gene in androgen receptor-negative prostate cancer cells via the GR-FOXO3a-GAS5 axis. Our results suggested patients with prostate cancer should be classified and develop a treatment plan according to the expression of AR and GR.

Analysis of biopsy pathology and risk factors of lymph node metastasis in prostate cancer.

OBJECTIVE: To explore the relationship between biopsy pathology and lymph node metastasis in patients with prostate cancer (PCa), and to identify risk factors of lymph node metastasis (LNM). PATIENTS AND METHODS: Patients diagnosed with prostate cancer were respective screened between Jan 2015 and May 2022. Patients diagnosed PCa via 13-core ultrasound-guided biopsies and underwent radical prostatectomy and lymph node dissection were identified. The clinicopathological characteristics of the patients were recorded. Relationships between LNM and non-LNM were analyzed using chi-square and independent samples t-test. Logistic regression model was fitted to analyze the risk factors of lymph node metastases. RESULTS: Two hundreds and fifteen patients were included, sixty-seven patients had lymph node metastasis. Gleason scores in LNM group were higher than that in non-LNM group (8.5 ± 0.9 VS 7.5 ± 1.5, p < 0.001), positive biopsy in non-LNM group was significantly lower than that in LNM group (p < 0.001), Binary logistic regression analysis indicated number of positive biopsy and number of removed lymph nodes increased the risks of LNM (odds ratio, OR = 1.28, 95% confidence interval, CI = 1.16-1.42, p < 0.001; OR = 1.11, 95% CI = 1.06-1.17, p < 0.001; respectively). Number of positive biopsy in internal gland but not external gland was significant associated with LNM (OR = 1.66, 95% CI = 1.34-2.06, p < 0.001; OR = 1.19, 95% CI = 0.88-1.61, p = 0.262; respectively). The patients with lymph nodes dissection more than 13 were about four times more likely to detect lymph node metastasis than those fewer than 13 (OR = 3.92, 95% CI = 2.10-7.33, p < 0.001). CONCLUSIONS: The risk of lymph node metastasis increased with the number of positive prostate biopsy cores, and tumors in the internal gland were more likely to cause lymph node metastasis. In addition, lymph node metastasis was more likely to be found when the number of lymph nodes dissection was greater than 13.

Social capital and loneliness among older adults in community dwellings and nursing homes in Zhejiang Province of China.

Background: Loneliness is an important problem afflicting the health of older adults, and has been proven to be associated with social capital. Previous research in China rarely investigated the differences of social capital and loneliness between older adults living in community dwellings and nursing homes. This study aims to examine the status of social capital and loneliness among older adults living in community dwellings and nursing homes, and analyze the relationship between them. Methods: A total of 1,278 older adults were recruited for the study from the cities of Hangzhou, Huzhou, and Lishui in Zhejiang Province of China from July to October 2021 by using multi-stage stratified random sampling. Questionnaires were used to collect data on the participants' sociodemographic characteristics, social capital, and loneliness. Hierarchical multiple regression was used to examine the relationship between social capital and loneliness. The interaction of social capital and institutionalization on loneliness was also explored. Results: Compared with community-dwelling older adults, institutionalized older adults had higher levels of loneliness and lower degrees of social support, social connection, trust, cohesion, and reciprocity. A further analysis of the social capital showed that low levels of social support, trust, and cohesion were related to high levels of loneliness among adults in both community dwellings and nursing homes. Social connection was negatively correlated with loneliness among older adults living in community dwellings. Institutionalization itself demonstrated a strong effect on loneliness. Conclusion: Health-related policies should help older adults gain more social support, trust and cohesion to alleviate their loneliness. This is particularly crucial for older adults living in nursing homes, as they have higher levels of loneliness and lower levels of social capital than noninstitutionalized older adults.

Effectiveness of mHealth management with an implantable glucose sensor and a mobile application among Chinese adults with type 2 diabetes.

INTRODUCTION: This study aimed to evaluate the effectiveness of mHealth management with an implantable glucose sensor and a mobile application among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: A randomised controlled trial was carried out to compare the effectiveness of usual health management to mHealth management based on a model that consisted of the network platform, an implantable glucose sensor and a mobile app featuring guidance from general practitioners (GPs) over a four-week period. Patients (N=68) with T2DM were randomly divided into an intervention group and a control group. Before the intervention, there was no difference in body mass index (BMI), fasting blood glucose (FBG), postprandial two-hour blood glucose (2hPG) and glycosylated haemoglobin (HbA1c) between the intervention group and the control group (p>0.05). Patients in the control group received their usual health management, while patients in the intervention group received mHealth management. RESULTS: After health management, the mean BMI, FBG, 2hPG and HbA1c of the intervention group patients were all lower than those of the control group patients (p < 0.05), and the quality of life and self-management of the intervention group patients had significantly improved. DISCUSSION: mHealth management effectively showed significant reductions in BMI, FBG, 2hPG and HbA1c and improved quality of life and self-management among patients, which may be related to real-time feedback from an implantable glucose sensor and guidance from GPs through a mobile app. mHealth management is a very promising way to promote the health management of T2DM in China, and this study provides a point of reference for mHealth management abroad.

The Effectiveness of a Specialized Nursing Team Intervention in the Unplanned Interruption of Continuous Renal Replacement Therapy.

Background: To explore the application of specialist nursing teams in patients undergoing unplanned interruptions in continuous renal replacement therapy. Methods: Sixty-six patients admitted to the intensive care unit of Jiangsu Province Hospital, China for continuous renal replacement therapy (CRRT) and experienced unplanned interruptions from Aug 2020 to Mar 2021 were enrolled as study subjects. Twenty four patients with conventional care were taken as the control group, and 42 patients in the specialized nursing team were taken as the experimental group. The age, type of disease, and degree of illness of the two groups were statistically processed and the differences were not significant (P>0.05) and were comparable. The control group received routine CRRT care after CRRT rescue, and the experimental group received CRRT care model from a specialized nursing team. Results: Patients in the group with specialized nursing care had 49 instances of CRRT unplanned interruptions, and the routine care group had 79 instances of CRRT unplanned interruptions. The number of unplanned interruptions in the experimental group was less than that of the control group, and the difference was statistically significant (P<0.001). The incidence of complications in the experimental group were lower than that of the control group (P<0.05). The satisfaction and quality of life of nurses in the specialist nursing group were clearly lower than those of the control group, and the difference was statistically significant (P<0.05). Conclusion: Specialist nursing teams could reduce the occurrence of unplanned interruptions in CRRT patients in intensive care and allow patients to receive continuity of care.

Status of traditional Chinese medicine healthcare services in nursing homes across China.

This study aimed to elucidate the status of traditional Chinese medicine (TCM) healthcare services provided in nursing homes across China. We investigated 484 nursing homes using self-compiled questionnaires with a convenient sampling method. Chi-squared and Wilcoxon rank-sum tests were used for univariate analysis and binary logistic regression for multi-factor analysis. Of the 443 nursing homes finally included, 215 (48.5%) provided TCM healthcare services. Nursing home leaders majored in integrated TCM and Western medicine, leaders with a better understanding of TCM and government policies, nursing homes charging over 5,000 CNY/month, and those with ≥500 beds were more likely to provide improved TCM healthcare services. Massage, moxibustion, cupping or scraping, plaster therapy, decocting pieces, and acupuncture were the most prevalent and popular TCM services. Lack of professionals, financial investment, and policy support were the most common factors limiting the provision of TCM healthcare services in Chinese nursing homes.

Analysis of related factors of radiation pneumonia caused by precise radiotherapy of esophageal cancer based on random forest algorithm.

The precise radiotherapy of esophageal cancer may cause different degrees of radiation damage for lung tissues and cause radioactive pneumonia. However, the occurrence of radioactive pneumonia is related to many factors. To further clarify the correlation between the occurrence of radioactive pneumonia and related factors, a random forest model was used to build a risk prediction model for patients with esophageal cancer undergoing radiotherapy. In this study, we retrospectively reviewed 118 patients with esophageal cancer confirmed by pathology in our hospital. The health characteristics and related parameters of all patients were analyzed, and the predictive effect of radiation pneumonia was discussed using the random forest algorithm. After treatment, 71 patients developed radioactive pneumonia (60.17%). In univariate analyses, age, planning target volume length, Karnofsky performance score (KPS), pulmonary emphysema, with or without chemotherapy, and the ratio of planning target volume to planning gross tumor volume (PTV/PGTV) in mediastinum were significantly associated with radioactive pneumonia (P < 0.05 for each comparison). Multivariate analysis revealed that with or without pulmonary emphysema (OR = 7.491, P = 0.001), PTV/PGTV (OR = 0.205, P = 0.007), and KPS (OR = 0.251, P = 0.011) were independent predictors for radiation pneumonia. The results concluded that the analysis of radiation pneumonia-related factors based on the random forest algorithm could build a mathematical prediction model for the easily obtained data. This algorithm also could effectively analyze the risk factors of radiation pneumonia and formulate the appropriate treatment plan for esophageal cancer.

Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors.

Objective: A low concentration of plasma triiodothyronine (T3) indicates euthyroid sick syndrome (ESS), which could be associated with a poor outcome in patients in intensive care units (ICUs). This study evaluated the relationship between ESS and prognostic indicators in patients admitted to an ICU and examined the free T3 (FT3) cut-off points that could be associated with 28-day mortality. Methods: This prospective observational study included patients admitted to the ICU of The Third Hospital of Hebei Medical University between February and November 2018. Baseline variables and data on the occurrence of low FT3 were collected. The patients were divided into ESS (FT3 < 3.28 pmol/L) and non-ESS groups. The relationship between ESS and prognostic indicators in patients admitted to the ICU was evaluated, and the FT3 cut-off points that could be associated with 28-day mortality were examined. Results: Out of a total of 305 patients, 118 (38.7%) were in the ESS group. Levels of FT3 (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and hospitalization expenses in the ICU (P = 0.001) were higher in the ESS group. A univariable analysis identified ESS, FT3, free thyroxine (FT4)/FT3, the APACHE II score, the sequential organ failure (SOFA) score, the duration of mechanical ventilation, creatinine (CREA) levels, the oxygenation index (HGB), white blood cells, albumin (ALB) levels, age, and brain natriuretic peptide (BNP) levels as factors associated with 28-day mortality (all P < 0.05). The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L, and the 28-day mortality rate and hospitalization expenses in the ICU were higher in patients with ESS. The syndrome was confirmed to be independently associated with 28-day mortality. Conclusion: This study determined the incidence of ESS in the comprehensive ICU to be 38.7%. APACHE II, SOFA, BNP, APTT, HGB, PLT, CREA, ALB, FT4, SBP, and DBP are closely related to ESS, while BNP, PLT, and ALB are independent risk factors for the syndrome.

Percutaneous vs Laparoscopic Treatment for Simple Renal Cysts: A Meta-analysis.

Objective: To compare the percutaneous and laparoscopic treatment for renal cyst to determine the optimal therapy for patients with renal cyst. Materials and Methods: A systematic search of PubMed, Cochrane Library, Web of Science, and EMBASE databases was conducted for articles published through June 3, 2020, using the preferred reporting items for systematic reviews and meta-analyses guidelines. Results: We found 493 studies from databases, and 6 were considered for the evidence synthesis. A total of 1631 cases were included. Of these patients, 488 cases underwent laparoscopic treatment and 1143 cases underwent percutaneous treatment. Symptomatic and radiologic success were higher for laparoscopic treatment (odds ratio [OR], OR = 3.59, confidence interval [95% CI], 1.45-8.88, p = 0.006; and OR = 7.46, 95% CI 3.99-13.94, p < 0.00001, respectively). Minor or severe complications were similar between the two treatments (OR = 1.54, 95% CI 0.40-5.98, p = 0.53; OR = 3.13, 95% CI 0.03-359.76, p = 0.64, respectively). Conclusion: Laparoscopic treatment for renal cyst was associated with better symptomatic and radiologic success, and its complication was no more than percutaneous treatment.

Standard versus mini-percutaneous nephrolithotomy for renal stones: a meta-analysis.

OBJECTIVES: To compare the standard percutaneous nephrolithotomy and mini-percutaneous nephrolithotomy in order to determine the optimal tract size for patients with renal stones. METHODS: A systematic search of Web of Science, EMBASE, Cochrane Library, and PubMed databases was conducted for articles published through 20 August 2019, reporting on a comparison of the standard percutaneous nephrolithotomy and mini-percutaneous nephrolithotomy using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 763 studies, 14 were considered for the evidence synthesis. A total of 1980 cases were included. Of these patients, 897 cases underwent standard percutaneous nephrolithotomy, and 1083 cases underwent mini-percutaneous nephrolithotomy. Stone-free rates were 87.6% (786 of 897 patients) for standard percutaneous nephrolithotomy and 87.8% (951 of 1083 patients) for mini-percutaneous nephrolithotomy (p = 0.57). Tract sizes of 30F and 22-26F in standard percutaneous nephrolithotomy group shorten operation time compared with mini-percutaneous nephrolithotomy (p = 0.02; p = 0.004; respectively). Leakage (p = 0.04), bleeding (p = 0.01), blood transfusion (p < 0.00001), and renal pelvis perforation (p = 0.02) were more common in standard percutaneous nephrolithotomy group than in mini-percutaneous nephrolithotomy group. Subgroup analysis showed only blood transfusion for 30F and 22-26F standard percutaneous nephrolithotomy group was more common than mini-percutaneous nephrolithotomy (p < 0.0001, p = 0.005, respectively). CONCLUSIONS: Standard percutaneous nephrolithotomy was associated with higher leakage, bleeding, blood transfusion, and renal pelvis perforation, but had a shorter operation time. Tract size of 30F improved the stone-free rate compared with mini-percutaneous nephrolithotomy, but led to more complications. Tract size of 22-26F was no better than 30F or mini-percutaneous nephrolithotomy.

Prognostic value of serum aquaporin-1, aquaporin-3 and galectin-3 for young patients with colon cancer.

BACKGROUND: This study aimed to investigate the long-term prognosis value of serum galectin-3, aquaporin (AQP)-1 and AQP-3 in young patients with colon cancer. METHODS: A total of 100 young patients with colon cancer, 100 cases of benign colon and 100 healthy people were collected. All colon cancer patients were followed up for 42 months. RESULTS: Compared with the benign lesion group and the control group, preoperative serum galectin-3, AQP-1 and AQP-3 concentrations were significantly increased in patients with colon cancer (P < 0.05). The immunohistochemistry scores of galectin-3, AQP-1 and AQP-3 in colon cancer patients were positively correlated with serum galectin-3, AQP-1 and AQP-3 concentrations (P < 0.05). Serum galectin-3, AQP-1 and AQP-3 concentrations were positively correlated with TNM staging (galectin-3: rPearson = 0.502, P < 0.001; AQP-1: rPearson = 0.415, P < 0.001; AQP-3: rPearson = 0.454, P < 0.001) and differentiation (galectin-3: rPearson = 0.377, P = 0.004; AQP-1: rPearson = 0.411, P = 0.001; AQP-3: rPearson = 0.483, P < 0.001). Receiver operator characteristic curve (ROC) analysis showed that the area under ROC curve (AUC) of the combination of galectin-3, AQP-1 and AQP-3 in distinguishing colon cancer was 0.907. The sensitivity in the parallel mode was 87.6%, and the specificity in the serial mode was 98.2%. Compared with the low galectin-3 group, low AQP-1 group and low AQP-3 group, the survival time of patients in the high galectin-3 group (χ2 = 13.929, P < 0.001), high AQP-1 group (χ2 = 10.157, P = 0.001) and high AQP-3 group (χ2 = 4.364, P = 0.037) were significantly shortened. CONCLUSION: Galectin-3 combined with AQP-1 and AQP-3 had important value in the identification of young patients with colon cancer and was of great value in evaluating long-term prognosis.

Prognostic Value of Thyroid Hormone FT3 in General Patients Admitted to the Intensive Care Unit.

Low plasma triiodothyronine (T3) concentration indicates nonthyroidal illness syndrome (NTIS), which might be associated with a poor outcome in patients in the intensive care unit (ICU). This study evaluated the relationship between NTIS and prognostic indicators in patients admitted to the ICU and examined the fT3 cut-off points that could be associated with 28-day mortality. This prospective observational study included patients admitted to the ICU of The Third Hospital of Hebei Medical University from February to November 2018. The baseline variables and the occurrence of low free T3 (FT3) were collected. The patients were divided into the NTIS (FT3 < 3.28) and non-NTIS groups. Among 305 patients, 118 (38.7%) were in the NTIS group. FT3 (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and hospitalization expenses in ICU (P = 0.001) were higher in the NTIS group. The univariable analyses identified NTIS, FT3, free thyroxine/FT3, APACHEII, sequential organ failure score, duration of mechanical ventilation, creatinine, oxygenation index, white blood cells, albumin, age, and brain natriuretic peptide as being associated with 28-day mortality (all P < 0.05). The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L. The 28-day mortality rate and hospitalization expenses in the ICU were higher in patients with NTIS. NTIS was independently associated with 28-day mortality.

Loss-of-function variants in FSIP1 identified by targeted sequencing are associated with one particular subtype of mucosal melanoma.

BACKGROUND: Mucosal melanoma is a tumor caused by the malignant transformation of pigment-producing cells and can arise from any mucosal tissue where melanocytes are present. Due to its rarity, the mucosal melanoma subtype is poorly described, and its genetic characteristics are infrequently studied. The discovery or confirmation of new mucosal melanoma susceptibility genes will provide important insights for the study of its pathogenesis. MATERIALS AND METHODS: We performed deep targeted sequencing of 100 previously reported melanoma-related genes in 39 mucosal melanoma samples and a gene-level loss-of-function (LOF) variant enrichment analysis for mucosal melanoma from different incidence sites. RESULTS: We detected 7,589 variants in these samples, and 484 were LOF variants (gain or loss of a stop codon, missense, and splice site). Four different gene-level enrichment analyses revealed that FSIP1 (fibrous sheath interacting protein 1) is a susceptibility gene for oral mucosal melanoma (OR = 0.33, PChi = 4.05 × 10-2, Pburden = 3.06 × 10-2, Pskat = 3.01 × 10-2, Pskato = 3.01 × 10-2), whereas the different methods did not detect a significant susceptibility gene for the other subtypes. CONCLUSIONS: In our study, a susceptibility gene for oral mucosal melanoma was confirmed in a Chinese Han population, and these findings contribute to a better genetic understanding of mucosal melanoma of different subtypes.

A comparison of the prognosis of papillary and clear cell renal cell carcinoma: Evidence from a meta-analysis.

OBJECTIVE: To compare the prognosis of papillary and clear cell renal cell carcinoma (RCC) in order to determine the optimal follow-up and therapy for patients with RCC. METHODS: A systematic search of Web of Science, EMBASE, Cochrane Library, and PubMed databases was conducted for articles published through July 30, 2018, reporting on a comparison of the prognosis of papillary RCC and clear cell RCC using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Of 1896 studies, 11 were considered for the evidence synthesis. A total of 35,832 patients were included. Of these patients, 6907 patients were diagnosed with papillary renal cell carcinoma, and 28,925 patients were diagnosed with clear cell renal cell carcinoma. The prognosis of papillary RCC was better than that of clear cell RCC (hazard ratio (HR) = 0.50; 95% confidence interval (CI) 0.45 to 0.56; P < .001; I = 91.9%). A subgroup analysis indicated that papillary RCC was associated with better outcomes (HR = 0.76, 95% CI 0.50-1.16), and a trend toward a higher risk of mortality was observed in patients with metastatic RCC presenting with papillary histology, but the difference was not statistically significant (HR = 1.12, 95% CI 0.71-1.76, P = .085). Pooled data suggested a lack of a significant difference between papillary RCC (p-RCC) type 1 and clear cell RCC (cc-RCC) (HR = 0.30, 95% CI 0.12-0.73, P = .085). The pooled HR for the prognosis of p-RCC type 2 compared to cc-RCC was 1.69 (95% CI 0.93-3.08; P = .032). CONCLUSION: Papillary RCC is associated with better outcomes than clear cell RCC in patients without metastases, but not in patients with metastases. Optimal follow-up or therapy for patients with RCC should be assigned according to the tumor stage and subtype.

Relationship between cFGF23/Klotho ratio and phosphate levels in patients with chronic kidney disease.

PURPOSE: To characterize the relationship between the cFGF23/Klotho ratio and phosphate level in patients with chronic kidney disease (CKD). METHODS: A total of 152 patients with CKD stage 3-5 (CKD stage 3: n = 74; CKD stage 4: n = 60; CKD stage 5: n = 18) were included in the study. Thirty healthy volunteers served as controls. Intact-FGF23, cFGF23, Klotho, serum calcium, serum phosphate, and serum creatinine were measured, and estimated glomerular filtration rate (eGFR) was calculated. The Kruskal-Wallis H test was used for comparison between groups, and the Spearman test was used for correlation analysis. RESULTS: In CKD stage 3-5, creatinine and iFGF23 levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), phosphate levels were higher (P < 0.05), and Klotho levels were lower (P < 0.01), compared with controls. C-terminal-FGF23 levels were higher in CKD phase 4-5 (P < 0.05). In CKD stage 4-5, creatinine, iFGF23, and phosphate levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), cFGF23 levels were higher (P < 0.05), and Klotho levels were lower (P < 0.05), compared with CKD stage 3. In CKD stage 5, creatinine and cFGF23 levels, as well as the cFGF23/Klotho ratio, were higher (P < 0.01), phosphate and iFGF23 levels were higher (P < 0.05), and Klotho levels were lower (P < 0.01), compared with CKD stage 4. Phosphate was positively correlated with the cFGF23/Klotho ratio (r = 0.235, P < 0.01). CONCLUSIONS: EGFR reduction was associated with an increased cFGF23/Klotho ratio, and the cFGF23/Klotho ratio was positively correlated with phosphate. This suggests that the phosphate level can be controlled by modifying the cFGF23/Klotho ratio.

Overexpression of Kin of IRRE-Like Protein 1 (KIRREL) in Gastric Cancer and Its Clinical Prognostic Significance.

BACKGROUND The aim of this study was to examine the expression level of IRRE-like protein 1 (KIRREL) in gastric cancer (GC) and to explore its prognostic significance. MATERIAL AND METHODS Bioinformatics methods were used to predict the differential expression levels of KIRREL mRNA in GC and normal gastric tissues by mining cancer-related databases (TCGA and Oncomine). Immunohistochemistry was done to verify the KIRREL protein expression levels in 71 cases of GC tissues combined with matched normal tissues. The relationship between clinicopathologic parameters and KIRREL differential expression levels in GC was investigated by the chi-square test. Kaplan-Meier univariate and Cox multivariate survival analyses were performed to explore the prognostic significance of KIRREL expression in GC patients. RESULTS TCGA and GEO data analyses showed that KIRREL mRNA expression level was remarkably higher in GC than that in normal gastric tissues (both P<0.05). KIRREL mRNA levels were dramatically increased from stage I to stage IV (P=0.037). Immunohistochemical results showed that the high positive rate of KIRREL staining in GC was 61.97% (44/71). Moreover, GC patients with KIRREL mRNA or protein high levels had significantly shorter overall survival times than those with KIRREL mRNA or low protein levels (All P<0.05). Additionally, Cox multivariate survival analysis revealed that KIRREL differential expression levels (low vs. high) were the only independent parameter predicting the prognosis of GC patients (P=0.000). CONCLUSIONS KIRREL was overexpressed in GC and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in GC patients.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.

Androgen receptor reverts dexamethasone­induced inhibition of prostate cancer cell proliferation and migration.

The aim of the present study was to determine the role of androgen receptor in the effect of dexamethasone on cell proliferation and migration of multiple prostate cancer cells. The prostate cancer cell lines LNCaP, 22Rv1, C4­2 and PC3 were cultured in vitro. For glucocorticoid­induced experiments, the cells were transferred and cultured in RPMI­1640 medium with 10% charcoal­stripped serum from RPMI­1640 medium with 10% fetal bovine serum for at least 24 h. The effects of dexamethasone on the proliferation and migration of various cell lines were analyzed by MTT and migration assays. Dexamethasone exhibited no effect on LNCaP, C4­2 and 22Rv1 cell lines, but suppressed proliferation of glucocorticoid receptor (GR)+ androgen receptor (AR)­ PC3 cell line. Dexamethasone suppressed PC3 cell migration, and did not affect migration of PC3­AR9 cells. Dexamethasone positively or negatively regulated proliferation of various prostate cancer cells based on AR and GR expression profiles. The data presented in the present study indicates that androgen receptor reverts the dexamethasone­induced inhibition of prostate cancer cell proliferation and migration.

Promoter methylation of DAPK gene may contribute to the pathogenesis of nonsmall cell lung cancer: a meta-analysis.

We performed a meta-analysis of cohort studies to determine whether promoter methylation of the death-associated protein kinase (DAPK) gene contributes to the pathogenesis of nonsmall cell lung cancer (NSCLC). A range of electronic databases were searched: MEDLINE (1966 ∼ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ∼ 2013), CINAHL (1982 ∼ 2013), Web of Science (1945 ∼ 2013), and the Chinese Biomedical Database (CBM; 1982 ∼ 2013) without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Our meta-analysis integrated results from 12 clinical cohort studies that met all inclusion criteria with a total of 1,027 NSCLC patients. We observed that the frequency of DAPK gene methylation in cancer tissues were significantly higher than that in the adjacent normal and benign tissues (cancer tissues vs. benign tissues: OR=8.50, 95 % CI=5.88 ∼ 12.28, P<0.001; cancer tissues vs. adjacent tissues: OR=5.95, 95 % CI=4.11 ∼ 8.60, P<0.001; cancer tissues vs. normal tissues: OR=4.75, 95 % CI=3.28 ∼ 6.87, P<0.001; respectively). Subgroup analysis by ethnicity demonstrated that DAPK gene methylation was closely associated with the development and progression of NSCLC among both Asians and Caucasians (all P<0.05). Furthermore, we conducted a subgroup analysis based on sample source and discovered that DAPK gene methylation was implicated in the pathogenesis of NSCLC in both blood and tissue subgroups (all P<0.05). Our results suggest that DAPK promoter methylation may be involved in NSCLC carcinogenesis. Thus, the detection of aberrant DAPK methylation may be helpful in the diagnosis and prognosis of NSCLC.

Molecular cloning, expression and enzymatic characterization of glutathione S-transferase from Antarctic sea-ice bacteria Pseudoalteromonas sp. ANT506.

A glutathione S-transferase (GST) gene from Antarctic sea-ice bacteria Pseudoalteromonas sp. ANT506 (namely PsGST), was cloned and expressed in Escherichia coli. The open reading frame of PsGST comprised 654 bp encoding a protein of 217 amino acids with a calculated molecular size of 24.3 kDa. The rPsGST possesses the conserved amino acid defining the binding sites of glutathione (G-site) and substrate binding pocket (H-site) in GST N_3 family. PsGST was expressed in E. coli and the recombinant PsGST (rPsGST) was purified by Ni-affinity chromatography with a high specific activity of 74.21 U/mg. The purified rPsGST showed maximum activity at 40 °C and exhibited 14.2% activity at 0 °C. It was completely inactivated at 50 °C for 40 min. These results indicated that rPsGST was a typical cold active GST with low thermostability. The enzyme was little affected by H2O2 and Triton X-100, and 50.2% of the remaining activity was detected in the presence of high salt concentrations (2M NaCl). The enzymatic Km values for CDNB and GSH was 0.22 mM and 1.01 mM, respectively. These specific enzyme properties may be related to the survival environment of Antarctic sea ice bacteria.