[Correlation between adipokine and clinicopathological features and prognosis in upper tract urothelial carcinoma].

OBJECTIVE: To investigate the correlation between expression levels of adipokine and clinicopathological features and prognosis of patients with upper tract urothelial carcinoma (UTUC) based on immunohistochemical staining and bioinformatics analysis. METHODS: The 8 adipokines in this study included adiponectin (AdipoQ), leptin (LEP), interleukin (IL)-6, IL-10 and their receptors (AdipoR1, AdipoR2, LEPR, IL-6R, IL-10RA, IL-10RB). Tissue samples of patients with UTUC who underwent surgical treatment in Peking University People's Hospital from January 2014 to April 2021 were selected for immunohistochemical staining. Their quantitative gene expression data were calculated by H-Score, and relevant clinical and follow-up data were collected retrospectively. Transcription group sequencing data of UTUC patients in Gene Expression Omnibus database (GSE134292 dataset) were downloaded for comparison. Chi-square test or t-test was used to compare the expression level of adipokine between non-muscle invasive group and muscle invasive group. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were utilized to analyze independent predictors of overall survival (OS), disease-free survival (DFS), intravesical recurrence-free survival (IVRFS) in the both cohorts. The P < 0.05 was considered statistically significant. RESULTS: In the study, 63 tissue samples of the patients with UTUC who underwent surgical treatment in Peking University People's Hospital and 57 UTUC patients in GSE134292 dataset were selected. In immunohistochemical cohort, the expressions of AdipoQ (P=0.003 6), AdipoR1 (P=0.006 5), LEP (P=0.007 7), IL-10 (P=0.006 9), and IL-10RA (P=0.008 9) were statistically higher in muscle invasive group. In GSE134292 cohort, the expressions of AdipoR1 (P=0.000 4), AdipoR2 (P=0.000 4), IL-6 (P=0.005 0), IL-10 (P=0.001 7), and IL-10RA (P=0.008 1) were statistically higher in muscle invasive group. Kaplan-Meier survival curve and multivariate Cox regression analysis showed that high IL-10RA expression was an independent predictive factor of IVRFS (P=0.044, HR=0.996, 95%CI: 0.992-0.998) in immunohistochemical cohort, which was confirmed in GSE134292 cohort (P=0.014, HR=0.515, 95%CI: 0.304-0.873). CONCLUSION: The expression levels of AdipoQ, AdipoR1, IL-10, and IL-10RA were correlated with tumor stage, suggesting that these adipokines played important roles in tumor progression. IL-10RA was an independent predictor of IVRFS, suggesting that IL-10 and its receptor played a critical role in tumor recurrence.

[Establishment of a mutation prediction model for evaluating the efficacy of immunotherapy in renal carcinoma].

OBJECTIVE: To establish a mutation prediction model for efficacy assessment, the genomic sequencing data of renal cancer patients from the MSKCC (Memorial Sloan Kettering Cancer Center) pan-cancer immunotherapy cohort was used. METHODS: The genomic sequencing data of 121 clear cell renal cell carcinoma patients treated with immune checkpoint inhibitors (ICI) in the MSKCC pan-cancer immunotherapy cohort were obtained from cBioPortal database (http://www.cbioportal.org/) and they were analyzed by univariate and multivariate Cox regression analysis to identify mutated genes associated with ICI treatment efficacy, and we constructed a comprehensive prediction model for drug efficacy of ICI based on mutated genes using nomogram. Survival analysis and time-dependent receiver operator characteristic curves were performed to assess the prognostic value of the model. Transcriptome and genomic sequencing data of 538 renal cell carcinoma patients were obtained from the TCGA database (https://portal.gdc.cancer.gov/). Gene set enrichment analysis was used to identify the potential functions of the mutated genes enrolled in the nomogram. RESULTS: We used multivariate Cox regression analysis and identified mutations in PBRM1 and ARID1A were associated with treatment outcomes in the patients with renal cancer in the MSKCC pan-cancer immunotherapy cohort. Based on this, we established an efficacy prediction model including age, gender, treatment type, tumor mutational burden (TMB), PBRM1 and ARID1A mutation status (HR=4.33, 95%CI: 1.42-13.23, P=0.01, 1-year survival AUC=0.700, 2-year survival AUC=0.825, 3-year survival AUC=0.776). The validation (HR=2.72, 95%CI: 1.12-6.64, P=0.027, 1-year survival AUC=0.694, 2-year survival AUC=0.709, 3-year survival AUC=0.609) and combination (HR=2.20, 95%CI: 1.14-4.26, P=0.019, 1-year survival AUC=0.613, 2-year survival AUC=0.687, 3-year survival AUC=0.526) sets confirmed these results. Gene set enrichment analysis indicated that PBRM1 was involved in positive regulation of epithelial cell differentiation, regulation of the T cell differentiation and regulation of humoral immune response. In addition, ARID1A was involved in regulation of the T cell activation, positive regulation of T cell mediated cyto-toxicity and positive regulation of immune effector process. CONCLUSION: PBRM1 and ARID1A mutations can be used as potential biomarkers for the evaluation of renal cancer immunotherapy efficacy. The efficacy prediction model established based on the mutation status of the above two genes can be used to screen renal cancer patients who are more suitable for ICI immunotherapy.

[Application of apparent diffusion coefficient combined with serum tumor markers detection in evaluating neoadjuvant chemotherapy for osteosarcoma].

Objective: To discuss application of apparent diffusion coefficient (ADC) in diffusion weighted imaging (DWI) combined with serum alkaline phosphatase (ALP) and tumor specific growth factor (TSGF) in evaluating neoadjuvant chemotherapy for osteosarcoma. Methods: A total of 78 patients with osteosarcoma who were admitted to People's Hospital of Gansu from January 2016 to August 2018 were collected as study subjects. All the patients were treated with neoadjuvant chemotherapy. Before chemotherapy, at the end of 4 courses of chemotherapy, before and after surgery, MRI examination and detection of serum ALP and TSGF were performed. According to results of pathological examination, the 78 patients were divided into effective chemotherapy group (n=54) and ineffective chemotherapy group (n=24). ADC values, levels of serum ALP and TSGF, change rates of ADC values and levels of serum ALP and TSGF were compared between the two groups. The value of ADC value combined with serum ALP and TSGF in evaluating curative effect of neoadjuvant chemotherapy for osteosarcoma was analyzed with receiver operating characteristic curve (ROC). Results: After chemotherapy, ADC value in effective chemotherapy group increased significantly, while levels of serum ALP and TSGF decreased significantly (t=7.269, 18.778, 23.237, all P<0.05). Only after surgery, ADC value, levels of serum ALP and TSGF increased or decreased significantly in ineffective chemotherapy group (t=7.316, 15.083, 20.930, all P<0.05). Before and after chemotherapy, change rates of ADC values and levels of serum ALP and TSGF in effective chemotherapy group were all significantly higher than those in ineffective chemotherapy group (t=7.604, 5.482, 5.048, all P<0.05). ROC curve analysis showed that area under the curve (AUC) of ADC value combined with serum ALP and TSGF for evaluating curative effect of neoadjuvant chemotherapy was 0.912, which was higher than that of ADC value, ALP, TSGF, ADC value combined with ALP, ADC value combined with TSGF (0.847, 0.787, 0.701, 0.885, 0.876, respectively). Conclusion: ADC value combined with serum tumor markers ALP and TSGF is reliable in evaluating curative effect of neoadjuvant chemotherapy for osteosarcoma.

Long non-coding RNA Dleu2 affects proliferation, migration and invasion ability of laryngeal carcinoma cells through triggering miR-16-1 pathway.

OBJECTIVE: Laryngeal cancer is a common malignant tumor in the head and neck, which affects swallowing, breathing, and pronunciation function. In recent years, many long non-coding RNAs (lncRNAs) have been shown to be involved in the progression of cancer with the development of gene sequencing, transcriptomics, and bioinformatics. LncRNA Dleu2 is a cancer-related lncRNA that down-regulates tumor progression in a variety of cancers. However, its possible effects and related signaling pathway in the development of laryngeal cancer are not clear. PATIENTS AND METHODS: Real-time PCR was applied to test lncRNA Dleu2 and microRNA-16-1 (miR-16-1) expressions in laryngeal carcinoma tissues. LncRNA Dleu2 and miR-16-1 levels were over-expressed by transfection. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration was evaluated by using wound-healing assay. Cell invasion was determined by using transwell assay. RESULTS: LncRNA Dleu2 and miR-16-1 levels were significantly declined in the laryngeal carcinoma tissue compared to para-carcinoma tissue (p < 0.05). LncRNA Dleu2 and miR-16-1 up-regulation significantly reduced cell proliferation, migration, and invasion compared to the control group (p < 0.05). Ago-miR16-1 transfection significantly enhanced the luciferase activity of wild-type Dleu2 compared to control group (p < 0.05), suggesting their interaction with each other. CONCLUSIONS: LncRNA Dleu2 influences the proliferation, migration, and invasion of laryngeal cancer cells through miR-16-1. Therefore, lncRNA Dleu2 and miR-16-1 may serve as potential biomarkers and targets for laryngeal cancer diagnosis and treatment.

miR-144-3p serves as a tumor suppressor by targeting FZD7 and predicts the prognosis of human glioblastoma.

OBJECTIVE: Previous research indicated that miR-144-3p was associated with the regulation of the carcinogenic processes, but the role of miR-144-3p in glioblastoma (GBM) remains unclear. In this study, we aimed to analyze the role of miR-144-3p in GBM. PATIENTS AND METHODS: The expression of miR-144-3p was measured in GBM tissues and adjacent non-malignant tissues using qRT-PCR. The correlation of miR-144-3p with clinicopathological features and prognosis was also analyzed. Cell proliferation, invasion, and migration assay were applied to assess the function of miR-144-3p in vitro. Bioinformatics prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Frizzled-7 (FZD7). The levels of FZD7 and FZD7 mRNA were determined by Western blot and RT-PCR. RESULTS: The results showed that the miR-144-3p expression was significantly downregulated in tumor tissues and GBM cell lines compared with that in normal brain tissues and the normal human astrocytes. The levels of miR-144-3p were negatively correlated with the status of WHO grade and recurrence. Furthermore, patients with low serum levels of miR-144-3p had a significantly shorter median overall survival rate. Multivariate Cox regression analysis confirmed that low level of miR-144-3p expression predicted poor prognosis independently. Further function assays showed that miR-144-3p inhibited proliferation invasion and migration of GBM cells. Finally, miR-144-3p was demonstrated to bind to the wild-type 3' untranslated region of FZD7 but not with its mutant. CONCLUSIONS: The results of the present study indicate that miR-144-3p suppresses tumor metastasis by targeting FZD7. This work also provides strong evidence that miR-144-3p is an independent prognostic factor for patients with GBM.

miR-182 selectively targets HOXA10 in goat endometrial epithelium cells in vitro.

Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.

Underwater superoleophobicity, anti-oil and ultra-broadband enhanced absorption of metallic surfaces produced by a femtosecond laser inspired by fish and chameleons.

Reported here is the bio-inspired and robust function of underwater superoleophobic, anti-oil metallic surfaces with ultra-broadband enhanced optical absorption obtained through femtosecond laser micromachining. Three distinct surface structures are fabricated using a wide variety of processing parameters. Underwater superoleophobic and anti-oil surfaces containing coral-like microstructures with nanoparticles and mount-like microstructures are achieved. These properties of the as-prepared surfaces exhibit good chemical stability when exposed to various types of oils and when immersed in water with a wide range of pH values. Moreover, coral-like microstructures with nanoparticle surfaces show strongly enhanced optical absorption over a broadband wavelength range from 0.2-25 µm. The potential mechanism for the excellent performance of the coral-like microstructures with a nanoparticle surface is also discussed. This multifunctional surface has potential applications in military submarines, amphibious military aircraft and tanks, and underwater anti-oil optical counter-reconnaissance devices.

Association of Resting Heart Rate with Infrarenal Aortic Diameter: A Cross Sectional Study in Chinese Hypertensive Adults.

OBJECTIVE: Elevated resting heart rate (RHR) has been shown to be a risk marker for cardiovascular disease. Results from studies on the effects of RHR in large arteries are limited to the functional changes of those arteries, while the association between RHR and aortic diameter remains largely understudied. METHODS: This was a cross sectional study of hypertensive Chinese adults from rural areas. The maximum infrarenal aortic diameter (maxIAD) from renal arteries to the iliac bifurcation was obtained by ultrasound. MaxIADs in different RHR groups were compared in males and females separately because of the significant differences between sexes. Multiple regression analysis was used to determinate the correlation between RHR and maxIAD. Further interactions between three factors (BMI, smoking, and anti-hypertensive regimens) and RHR for maxIAD were examined using subgroup analysis. RESULTS: 19,200 subjects were enrolled in the study, with an average age of 64.8±7.4 years and 61.6% females. Only 22 cases (0.11%) were detected with AAA, with males (n = 17) presenting a higher AAA incidence than females (n = 5). In subjects ≥65 years, there were 18 (0.19%) AAA, and 15 (83.3%) had a history of smoking. In the total subjects, the mean maxIAD ranged from 15.7±2.1 mm to 15.2±2.2 mm as RHR changed from the lowest quartile to the highest (≥84 bpm) in males, with a similar tendency observed in females. The correlation coefficient of RHR on maxIAD was -0.17 in males and -0.12 in females. Further subgroup analysis revealed that smoking exaggerated the correlation between RHR and maxIAD, but only in females. CONCLUSIONS: A low AAA incidence was observed in this hypertensive Chinese population. There was a negative association between RHR and maxIAD, potentially exaggerated by smoking, especially in females.

Association between the epithelial cadherin -160C/A gene polymorphism and diffuse gastric cancer risk: a meta-analysis.

Several previous studies have investigated whether the -160C/A epithelial cadherin promoter polymorphism confers an increased risk of diffuse gastric cancer (DGC), but conflicting results have been reported. To explore further the association of this polymorphism with DGC susceptibility, we performed an extensive search of relevant studies and conducted a meta-analysis to obtain a more precise estimate. We conducted a systematic literature search using the databases EMBASE, PubMed, and Web of Knowledge for reports published before August 2012 that met certain criteria. Information was carefully and independently extracted from all eligible publications by 2 of the authors. Twelve distinct data sets from 10 case-control studies were analyzed. They included 1115 cases of DGC and 2965 controls. Although none of the genotypes was associated with DGC risk, a slight trend of increased risk was found among A allele carriers [odds ratio (OR) = 1.237, 95% confidence interval (95%CI), 0.940-1.627], CA heterozygotes (OR = 1.229, 95%CI = 0.938-1.610), and AA homozygotes (OR = 1.146, 95%CI = 0.684-1.918). However, when the cases were stratified by ethnicity, a diverging trend occurred in AA homozygotes between the Asian group (OR = 0.710, 95%CI = 0.328-1.536) and its Caucasian counterpart (OR = 1.434, 95%CI = 0.657-3.131). Taken together, the summarized analyses of these case-control studies demonstrated that the -160A of the epithelial cadherin gene exhibited no significant association with susceptibility for DGC; however, the results suggested that it is a potential genetic risk factor in both Asians and Caucasians. Additional large-scale, well-designed studies are necessary to confirm whether AA homozygosity is a protective factor in Asians.

Polymorphisms of PRLR and FOLR1 genes and association with milk production traits in goats.

We investigated the polymorphisms of PRLR and FOLR1 genes in Xinong Saanen, Guanzhong, and Boer goat breeds by DNA sequencing and PCR-RFLP. Two novel SNPs were identified: KC109741: g.62130C>T in the 3ꞌ-UTR of goat gene PRLR, and KC136296: g.7884A>C in exon 3 of goat gene FOLR1. In the three goat breeds, the polymorphism information content was 0.20-0.27 at the g.62130C>T locus. At the g.7884A>C locus, it was 0.36 in Boer goats. The three goat breeds were in Hardy-Weinberg disequilibrium at the g.62130C>T locus. The g.62130C>T SNP was found to be significantly associated with milk production traits in Xinong Saanen and Guanzhong breeds. These results are consistent with the regulatory function of PRLR in mammary gland development, milk secretion, and expression of milk protein genes; they extend the spectrum of genetic variation of the goat PRLR gene, which could be useful for breeding programs.

Molecular cloning and characterization of KISS1 promoter and effect of KISS1 gene mutations on litter size in the goat.

Kisspeptins, the product of the KISS1 gene, play an essential role in the regulation of reproductive functions, acting primarily at the hypothalamic level of the gonadotropic axis. We detected polymorphisms of the goat KISS1 gene in 723 individuals from three goat breeds (Xinong Saanen, Guanzhong, and Boer) by DNA pooling, PCR-RFLP, and DNA sequencing methods. We cloned the promoter sequence of this gene and found it to share high similarity with that of the bovine KISS1 promoter. Six TATA boxes were found in the goat KISS1 promoter region. Two novel SNPs (g.2124T>A and g.2270C>T) were identified in the intron 1 of the KISS1 gene of all three goat breeds. The three goat breeds were in Hardy-Weinberg disequilibrium at g.2124T>A and g.2270C>T loci. The g.2124T>A and g.2270C>T loci were closely linked in the three goat breeds (r2 > 0.33). The g.2124T>A and g.2270C>T SNPs were significantly associated with litter size, and the C1 female goats had a larger litter size than did those with the other genotypes. These results extend the spectrum of genetic variation of the goat KISS1 gene, which contributes to our knowledge of goat genetic resources for breeding programs.

Polymorphism identification in goat GNRH1 and GDF9 genes and their association analysis with litter size.

This study investigated the polymorphisms of GNRH1 and GDF9 genes in 641 goats of three breeds: Xinong Saanen, Guanzhong and Boer. Two allelic variants were identified in the GNRH1 gene (JN645280:g.3548A>G and JN645281:g.3699G>A) and one allelic variant was found in the GDF9 gene (JN655693:g.4093G>A). Furthermore, g.4093G>A was a missense mutation (p.Val397Ile of GDF9). Results of an association analysis indicated that SNPs g.3548A>G and g.4093G>A had significant effects on litter size (P < 0.05). The combination genotypes of SNPs g.3548A>G, g.3699G>A and g.4093G>A also affected litter size with the C5 genotype having the highest litter size in the first, third, fourth and average parity. Hence, the biochemical and physiological functions, together with the results obtained in our investigation, suggest that the GNRH1 and GDF9 genes could serve as genetic markers for litter size in goat breeding.

A new approach for cloning hLIF cDNA from genomic DNA isolated from the oral mucous membrane.

Complementary DNA (cDNA) is valuable for investigating protein structure and function in the study of life science, but it is difficult to obtain by traditional reverse transcription. We employed a novel strategy to clone human leukemia inhibitory factor (hLIF) gene cDNA from genomic DNA, which was directly isolated from the mucous membrane of mouth. The hLIF sequence, which is 609 bp long and is composed of three exons, can be acquired within a few hours by amplifying each exon and splicing all of them using overlap-PCR. This new approach developed is simple, time- and cost-effective, without RNA preparation or cDNA synthesis, and is not limited to the specific tissues for a particular gene and the expression level of the gene.

Inhibition of human telomerase activity by alterperylenol.

Human telomerase is a ribonucleoprotein that maintains telomeres by adding TTAGGG tandem repeat sequences using RNA template of the enzyme. Telomerase activity is highly expressed in immortalized cells but not in most somatic cells, except for some renewal tissues, such as hematopoietic stem cells. Therefore, telomerase can be a target for anticancer drugs. Here we show that a fungus metabolite, alterperylenol, inhibits human telomerase activity. Alterperylenol inhibited telomerase activity (IC50 = 30 microM), but altertoxin I, a structurally related compound, did not affect it at 1 mM. Moreover, alterperylenol did not affect the activity of viral reverse transcriptase at 1 mM.

[Clinical analysis of 134 cases of central nervous system leukemia].

134 cases of central nervous system leukemia (CNSL) were reported. The clinical manifestations and the relationship of its occurrence with the duration of the disease and the effectiveness of prophylaxis were discussed. It was found that most cases of CNSL occurred 3 months after the diagnosis of leukemia. It was quite different from the reports in literature that most CNSL usually occurred after complete remission, with CSF routine examination the into cranial pressure, the protein content, the white cell count and the smear for leukemic cells were of significant diagnostic help. Among these, the founding of leukemic cells in the fresh specimen by using natural precipitation method is the most reliable diagnostic criterion of CNSL.