Gene mutation profiling and clinical significances in patients with renal cell carcinoma.

OBJECTIVES: The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. METHODS: Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. RESULTS: The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. CONCLUSIONS: Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

Characteristics of the microbiome in lung adenocarcinoma tissue from patients in Kunming city of southwestern China.

The purpose of this study is to identify the characteristics of microbial communities in the lung cancer tissues from patients in Kunming sity of southwestern China and to compare the microbial differences at different clinical stages of lung cancer to uncover potential microbial biomarkers. In total, 40 tissue samples of primary lung adenocarcinoma were collected and further performed by 16S rRNA gene sequencing. The subjects were grouped according to TNM stages (T and N group), clinical stage, and smoke status, and the microbial differences in each group were compared. Analysis of sequence data to determine beta diversity, the UniFrac distance was calculated by QIIME and visualized by principal coordinate analysis (PCoA) using R (version 2.15.3). Microbiome abundance and diversity between different groups were calculated by t test or Wilcoxon rank sum test and drawn by R. The linear discriminant analysis effect size (LEfSe) method was utilized to compare relative abundances of all bacterial taxa between groups. A total of 951 OTUs were identified in the cancer tissues. No significant difference has been found in the alpha diversity within all the groups. Beta diversity significantly differed in the N, T, and clinical stage groups. By LEfSe analysis, eight differential taxa including Bifidobacterium were identified in the N group. In the T1 and T2 group, the LEfSe result identified five phyla and ten genera. The differential genera were Moraxella, Dolosigranulum, unidentified_Corynebacteriaceae, and Citrobacter in the T2 group and Bifidobacterium, Alistipes, Akkermansia, Blautia, Lactobacillus, as well as Faecalibaculum in the T1 group. Differential bacterial composition and abundance were also observed in the clinical stage group. This study confirmed that by 16S rRNA sequencing, we identified the dominant microbe of lung cancer tissue in different groups. Bifidobacterium may play an essential role in lymph node metastasis and tumor progression, providing a specific potential microbial biomarker for lung adenocarcinoma. PCR products were subject to vertical electrophoresis on 2% agarose gels, and a colloid recovery kit (Qiagen, Valencia, CA) was applied to recover the target bands. Libraries were generated by the TruSeq DNA PCR-Free Sample Preparation Kit (Illumina, San Diego, USA), and the concentrations were quantitated with a Qubit fluorometer. Finally, the qualified libraries were sequenced by NovaSeq6000 (Illumina).

The clinical and genomic distinctions of Class1/2/3 BRAF-mutant colorectal cancer and differential prognoses.

BRAF mutations are the oncogenic drivers in colorectal cancer and V600 mutations (Class1), which lead to RAS-independent active monomers, are the most common mutation types. BRAF non-V600 mutants can be further classified as RAS-independent active dimers (Class2) and RAS-dependent impaired kinase (Class3). We retrospectively reviewed the mutational profiles of 328 treatment-naïve colorectal tumors with BRAF mutations detected using capture-based hybrid next-generation sequencing targeting 400 + cancer-related genes. The clinical and genetic distinctions of patients harboring Class1/2/3 BRAF mutations were investigated, which revealed that tumors with Class1 BRAF mutations showed more unique genomic profiles than those with Class2/3 mutations. Also, by using an external dataset from cBioPortal, we demonstrated that patients with Class3 BRAF mutations had the best survival outcomes compared to the other two subgroups. These findings promoted the development of anti-BRAF strategies by distinguishing BRAF mutant subgroups.

Gene mutation profiling and clinical significances in patients with renal cell carcinoma

Abstract Objectives The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. Methods Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. Results The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. Conclusions Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

Association of volunteer-administered home care with reduced emergency room visits and hospitalization among older adults with chronic conditions: A propensity-score-matched cohort study.

OBJECTIVES: The objective of this study was to examine the association of receiving care from a volunteer-administered outreach program with emergency room utilization and hospitalization among older people with chronic conditions in Hong Kong. METHODS: Volunteers consisting of retired healthcare professionals, university students, and openly recruited citizens received training to provide home care services to hospital-discharged older Chinese adults aged 65+ with chronic conditions who were identified as high-risk patients of hospital admission and referred by public healthcare providers. Several home visits were made to enhance the patients' self-care capacity. For comparison, a 4:1-propensity score matching based on age, sex, the month of discharge, length of stay for the index episode, and 14 common chronic conditions was conducted to select a comparison group from a territory-wide inpatient database. Poisson regression was used to compare emergency room utilization and the number of hospitalized days. RESULTS: In total, 775 patients were analyzed, including 155 home care recipients and 620 extracted from the inpatient database as a matched comparison with similar baseline characteristics. Regression analysis showed that home care recipients had 21% fewer overall emergency room visits [95% confidence interval (CI): 3%-35%], 22% fewer such visits which led to hospitalization (95% CI: 1%-39%) and 22% fewer overall hospitalized days (95% CI: 16%-28%). Nevertheless, the number of hospitalized days admitted through the emergency room was 10% higher among home care recipients (95% CI: 0%-20%). CONCLUSIONS: Volunteer-administered home care might be effective in reducing emergency room visits and non-acute hospitalization, as well as early detection of acute problems warranting tertiary care. Further randomized studies are needed to substantiate this finding.

Flight Muscle and Wing Mechanical Properties are Involved in Flightlessness of the Domestic Silkmoth, Bombyx mori.

Flight loss has occurred in many winged insect taxa. The flightless silkmoth Bombyx mori, is domesticated from the wild silkmoth, Bombyx mandarina, which can fly. In this paper, we studied morphological characteristics attributed to flightlessness in silkmoths. Three domestic flightless B. mori strains and one B. mandarina population were used to compare morphological components of the flight apparatus, including wing characteristics (shape, forewing area, loading, and stiffness), flight muscle (weight, ratio, and microscopic detail) and body mass. Compared with B. mandarina, B. mori strains have a larger body, greater wing loading, more flexible wings and a lower flight muscle ratio. The arrangement in microscopy of dorsal longitudinal flight muscles (DLFMs) of B. mori was irregular. Comparative analysis of the sexes suggests that degeneration of flight muscles and reduction of wing mechanical properties (stiffness) are associated with silkmoth flightlessness. The findings provide important clues for further research of the molecular mechanisms of B. mori flight loss.

Structure analysis of the spinneret from Bombyx mori and its influence on silk qualities.

Silk is an excellent natural fiber, which has been widely used in versatile fields. Silk spinning is a complex process involving the larval spinneret. The spinneret is essential for silk spinning, but the sectional morphology of the spinneret that determines the silk monofilament, the muscular activities around the silk press as well as the relationships between the spinneret and the properties of the resulting silk remain poorly understood. We studied these factors by dissecting the spinneret and analyzing silk from different Bombyx mori strains. The sectional morphology of silk monofilament was found to be largely determined by the spinneret, especially by the silk press. Moreover, contractile activity of the muscles around the silk press is high, and the contraction frequency of the muscles was estimated to range from 11.42 to 50 HZ. A comparison of the fibroin filaments before they entered the common tube indicated that the spinneret determines both silk shape and silk size. This study provides insight into the silk spinning process, which may help develop bionic spinning in further studies and also provides a rationale to study the effect of the spinneret on silk fineness at the molecular level.

p27 inhibits CDK6/CCND1 complex formation resulting in cell cycle arrest and inhibition of cell proliferation.

p27 plays critical roles in cell proliferation, differentiation, and apoptosis, which have been well studied in mammals and Drosophila. However, the mechanisms underlying p27 regulation of the cell cycle have not been thoroughly researched. In this study, Genevestigator, Kaplan-Meier Plotter, and the Human Protein Atlas databases were used to analyze the expression of p27, cell division protein kinase 6 (CDK6), and cyclin D1 (CCND1), as well as its prognostic value in different tumor tissues and corresponding normal tissues. Quantitative PCR and immunohistochemistry were used to detect the expression of p27, CDK6, and CCND1 in the tissues of cancer patients. The effects of p27, CDK6, and CCND1 on the proliferation of lung cancer cells were examined by the MTT assay, and flow cytometry was used to investigate the mechanism by which p27 affected cell proliferation. Immunofluorescence, co-immunoprecipitation, and Western blotting were used to determine if p27 interacted with CDK and CCND1 to regulate the cell cycle. The results showed that p27, CDK6, and CCND1 played different roles in tumorigenesis and development, which are in accordance with CDK6 and CCND1 in affecting the cell cycle and cell proliferation. p27 regulated the cell cycle and inhibited cell proliferation by affecting formation of the cell cycle-dependent complex CDK6/CCND1, but did not directly affect the expression of CDK6 and CCND1. Moreover, CCND1 did not regulate the cell cycle alone, but rather, functioned together with CDK6. This study provides insights into the effects of p27 on tumor formation and development, and the underlying regulatory mechanisms.

[An Exploration of the Pain Management Knowledge of Emergency Room Staffs and Factors of Influence].

BACKGROUND: Pain has been integrated as the fifth vital sign that is a common health problem for emergency room patients. Although prior studies have addressed the effects of the pain-management knowledge of emergency room staffs on the quality of pain care, there is a dearth of research on pain management knowledge and on the factors that influence this knowledge. PURPOSE: To explore the knowledge of emergency room staffs regarding pain management and the factors that influence this knowledge. METHODS: This cross-sectional study used a self-developed questionnaire to survey a convenience sample of 201 physicians and nurses from three emergency rooms in northern Taiwan. RESULTS: The average score for pain-management knowledge was 63.28 out of 100. Demographic variables including education level, professional specialty, and sources of pain education had significant effects on participants' pain-management knowledge. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The knowledge of emergency room staffs regarding pain management must be reinforced further in order to improve care quality. The factors identified that influence this knowledge may be referenced by hospitals in developing / revising pain-related continuing education, in developing pain management guidelines, and in setting the directions for future research on pain management.