The Immune Landscape of Cancer.

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-ß dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

Controllable Design of Metal-Organic Framework-Derived Vanadium Oxynitride for High-Capacity and Long-Cycle Aqueous Zn-Ion Batteries.

Introducing N atoms in vanadium oxides (VOx) of aqueous Zn-ion batteries (ZIBs) can reduce their bandgap energy and enhance their electronic conductivity, thereby promoting the diffusion of Zn2+. The close-packed vanadium oxynitride (VON) generated often necessitates the intercalation of water molecules for restructuring, rendering it more conducive for zinc ion intercalation. However, its dense structure often causes structural strain and the formation of by-products during this process, resulting in decreased electrochemical performance. Herein, carbon-coated porous V2O3/VN nanosheets (p-VON@C) are constructed by annealing vanadium metal-organic framework in an ammonia-contained environment. The designed p-VON@C nanosheets are efficiently converted to low-crystalline hydrated N-doped VOx during subsequent activation while maintaining structural stability. This is because the V2O3/VN heterojunction and abundant oxygen vacancies in p-VON@C alleviate the structural strain during water molecule intercalation, and accelerate the intercalation rate. Carbon coating is beneficial to prevent p-VON@C from sliding or falling off during the activation and cycling process. Profiting from these advantages, the activated p-VON@C cathode delivers a high specific capacity of 518 mAh g-1 at 0.2 A g-1 and maintains a capacity retention rate of 80.9% after 2000 cycles at 10 A g-1. This work provides a pathway to designing high-quality aqueous ZIB cathodes.

Purine permease (PUP) family gene PUP11 positively regulates the rice seed setting rate by influencing seed development.

KEY MESSAGE: Purine permease PUP11 is essential for rice seed development, regulates the seed setting rate, and influences the cytokinin content, sugar transport, and starch biosynthesis during grain development. The distribution of cytokinins in plant tissues determines plant growth and development and is regulated by several cytokinin transporters, including purine permease (PUP). Thirteen PUP genes have been identified within the rice genome; however, the functions of most of these genes remain poorly understood. We found that pup11 mutants showed extremely low seed setting rates and a unique filled seed distribution. Moreover, seed formation arrest in these mutants was associated with the disappearance of accumulated starch 10 days after flowering. PUP11 has two major transcripts with different expression patterns and subcellular locations, and further studies revealed that they have redundant positive roles in regulating the seed setting rate. We also found that type-A Response Regulator (RR) genes were upregulated in the developing grains of the pup11 mutant compared with those in the wild type. The results also showed that PUP11 altered the expression of several sucrose transporters and significantly upregulated certain starch biosynthesis genes. In summary, our results indicate that PUP11 influences the rice seed setting rate by regulating sucrose transport and starch accumulation during grain filling. This research provides new insights into the relationship between cytokinins and seed development, which may help improve cereal yield.

Is there any difference in urinary continence between bilateral and unilateral nerve sparing during radical prostatectomy? A systematic review and meta-analysis.

CONTEXT: In men with prostate cancer, urinary incontinence is one of the most common long-term side effects of radical prostatectomy (RP). The recovery of urinary continence in patients is positively influenced by preserving the integrity of the neurovascular bundles (NVBs). However, it is still unclear if bilateral nerve sparing (BNS) is superior to unilateral nerve sparing (UNS) in terms of post-RP urinary continence. The aim of this study is to systematically compare the differences in post-RP urinary continence outcomes between BNS and UNS. METHODS: The electronic databases of PubMed and Web of Science were comprehensively searched. The search period was up to May 31, 2023. English language articles comparing urinary continence outcomes of patients undergoing BNS and UNS radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk (RR) estimates with 95% confidence intervals for urinary continence in BNS and UNS groups at selected follow-up intervals using a random-effects model. Sensitivity analyses were performed in prospective studies and robotic-assisted RP studies. RESULTS: A meta-analysis was conducted using data from 26,961 participants in fifty-seven studies. A meta-analysis demonstrated that BNS improved the urinary continence rate compared to UNS at all selected follow-up points. RRs were 1.36 (1.14-1.63; p = 0.0007) at ≤ 1.5 months (mo), 1.28 (1.08-1.51; p = 0.005) at 3-4 mo, 1.12 (1.03-1.22; p = 0.01) at 6 mo, 1.08 (1.05-1.12; p < 0.00001) at 12 mo, and 1.07 (1.00-1.13; p = 0.03) at ≥ 24 mo, respectively. With the extension of the follow-up time, RRs decreased from 1.36 to 1.07, showing a gradual downward trend. Pooled estimates were largely heterogeneous. Similar findings were obtained through sensitivity analyses of prospective studies and robotic-assisted RP studies. CONCLUSION: The findings of this meta-analysis demonstrate that BNS yields superior outcomes in terms of urinary continence compared to UNS, with these advantages being sustained for a minimum duration of 24 months. It may be due to the real effect of saving the nerves involved. Future high-quality studies are needed to confirm these findings.

SOCS1 acts as a ferroptosis driver to inhibit the progression and chemotherapy resistance of triple-negative breast cancer.

OBJECTIVES: Ferroptosis is involved in many types of cancers, including triple-negative breast cancer (TNBC). Suppressor of cytokine signaling 1 (SOCS1) has recently been implicated as a regulator of ferroptosis. We aim to explore whether targeting SOCS1 is a potential therapeutic strategy for TNBC therapy. METHODS: Stable cell lines were constructed using lentivirus transfection. Cell viability was determined using CCK-8 and cell colony formation assays, respectively. Assays including lactate dehydrogenase release, lipid peroxidation and malondialdehyde assays were conducted to evaluate ferroptosis. Real-time quantitative polymerase chain reaction and western blotting were performed to evaluate mRNA and protein expression, respectively. A xenograft animal model was established by subcutaneous injection of cells into the flank. RESULTS: Our results showed that SOCS1 overexpression inhibited cell proliferation and induced ferroptosis in TNBC cells, while SOCS1 knockdown promoted cell proliferation and reduced ferroptosis. We also found that SOCS1 regulated ferroptosis by modulating GPX4 expression. Furthermore, SOCS1 regulated cisplatin resistance in TNBC cells by promoting ferroptosis. Our in vivo data suggested that SOCS1 regulated tumor growth and cisplatin resistance in vivo. CONCLUSIONS: SOCS1 inhibits the progression and chemotherapy resistance of TNBC by regulating GPX4 expression.

Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer.

BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer. METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival. RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma. CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools. PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.

Recent strategies for electrochemical sensing detection of miRNAs in lung cancer.

MicroRNAs (miRNAs) associated with lung cancer are diversifying. MiR-21, Let-7, and miR-141 are common diagnostic targets. Some new lung cancer miRNAs, such as miR-25, miR-145, and miR-126, have received increasing attention. Although various techniques are available for the analysis of lung cancer miRNAs, electrochemistry has been recognized for its high sensitivity, low cost, and rapid response. However, how to realize the signal amplification is one of the most important contents in the design of electrochemical biosensors. Herein, we mainly introduce the amplification strategy based on enzyme-free amplification and signal conversion, including non-linear HCR, catalytic hairpin assembly (CHA), electrochemiluminescence (ECL), and Faraday cage. Furthermore, new progress has emerged in the fields of nanomaterials, low oxidation potential, and simultaneous detection of multiple targets. Finally, we summarize some new challenges that electrochemical techniques may encounter in the future, such as improving single-base discrimination ability, shortening electrochemical detection time, and providing real body fluid samples assay.

Syntheses of Substituted α,ß-Unsaturated δ-Lactams from N-Boc-2,4-dioxopiperidine.

A method for the syntheses of substituted α,ß-unsaturated δ-lactams (2) from the commercially available compound N-Boc-2,4-dioxopiperidine (1) has been developed. The α-substituents were introduced by a reductive Knoevenagel condensation reaction, and the ß-substituents were installed by palladium-catalyzed cross coupling reactions. More than 20 diverse examples were prepared in 2-3 steps. The synthesis was operationally simple, user-friendly, and easy to scale up.

Cytokinin oxidase/dehydrogenase family genes exhibit functional divergence and overlap in rice growth and development, especially in control of tillering.

Cytokinins play key roles in plant growth and development, and hence their biosynthesis and degradation have been extensively studied. Cytokinin oxidase/dehydrogenases (CKXs) are a group of enzymes that regulate oxidative cleavage to maintain cytokinin homeostasis. In rice, 11 CKX genes have been identified to date; however, most of their functions remain unknown. In this study, we comprehensively examined the expression patterns and functions of the CKXs in rice by using CRISPR/Cas9 technology to construct mutants of all 11 genes. The results revealed that the ckx single-mutants and higher-order ckx4 ckx9 mutant lines showed functional overlaps and sub-functionalization. Notably, the ckx1 ckx2 and ckx4 ckx9 double-mutants displayed contrasting phenotypic changes in tiller number and panicle size compared to the wild-type. In addition, we identified several genes with significantly altered expression in both the ckx4 and ckx9 single-mutant and double-mutant plants. Many of the differentially expressed genes were found to be associated with auxin and cytokinin pathways, and cytokinins in the ckx4 ckx9 double-mutant were increased compared to the wild-type. Taken together, our findings provide new insights into the functions of CKX genes in rice growth and may provide the foundations for future studies aimed at improving rice yield.

LIMD2 promotes tumor proliferation, invasion, and epithelial-mesenchymal transition in clear cell renal cell carcinoma.

LIMD2 was found upregulated in various tumors and metastatic samples and associated with a poor prognosis. But the role of LIMD2 in clear cell renal cell carcinoma (ccRCC) remains elusive. The expression of LIMD2 in ccRCC was analyzed using cohort data downloaded from TCGA and ICGC databases. In vitro and in vivo experiments were then conducted to study the biological role of LIMD2 in ccRCC and explore the possible mechanism. The results indicated that LIMD2 was overexpressed and correlated with a poor outcome in ccRCC. LIMD2 promoted the malignancy of ccRCC both in vitro and in vivo. LIMD2 induced epithelial-mesenchymal transition (EMT) via activating the ILK/Akt pathway in ccRCC. In conclusion, LIMD2 is overexpressed and promotes proliferation, invasion, and EMT in ccRCC, which may serve as a potential novel therapeutic target for ccRCC.

Long non-coding RNA EWSAT1 promoted metastasis and actin cytoskeleton changes via miR-24-3p sponging in osteosarcoma.

Non-coding RNAs are closely associated with tumorigenesis in multiple malignant tumours, including osteosarcoma (OS). Long non-coding RNA Ewing sarcoma-associated transcript 1 (EWSAT1) plays a role in metastasis, and actin cytoskeletal changes in OS remain unclear. In the current study, we showed that EWSAT1 expression was up-regulated in OS and that an elevation in the EWSAT1 expression level was correlated with poor prognosis in patients with OS. Functionally, we showed that knockdown of EWSAT1 suppressed migration and induced actin stress fibre degradation in MNNG/HOS and 143B cells. Moreover, we found that ROCK1 was a key downstream effector in EWSAT1-mediated cell migration and actin stress fibre changes. Furthermore, we demonstrated that ROCK1 and EWSAT1 shared a similar microRNA response element of microRNA-24-3p (miR-24-3p). Moreover, we verified that miR-24-3p suppressed ROCK1 and its mediated migration and actin stress fibres change by direct targeting. EWSAT1 promoted ROCK1-mediated migration and actin stress fibre formation through miR-24-3p sponging. Lastly, through an in vivo study, we demonstrated that EWSAT1 promoted lung metastasis in OS. According to the above-mentioned results, we suggest that EWSAT1 acts as an oncogene and that EWSAT1/miR-24-3p/ROCK1 axial could be a new target in the treatment of OS.

Efficacy and Safety Evaluation of Transurethral Resection of the Prostate versus Plasmakinetic Enucleation of the Prostate in the Treatment of Massive Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common chronic progressive disease resulting in urinary obstruction in aging men. It comes to more and more patients with massive BPH with the aging of society and extension of life expectancy. OBJECTIVE: The aim of the study was to compare the clinical efficacy, safety, and complications between transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) in the treatment of massive BPH. DESIGN AND SETTING: Patients with BPH were divided into the PKEP group and the TURP group randomly. Intraoperative blood loss (BL), operation time (OT), resected tissue weight (RTW), gland resection ratio (GRR), postoperative indwelling ureter time (IUT), bladder fistula time (BFT) and hospital stay time (HST), preoperative and postoperative serum sodium concentration (SSC), hemoglobin concentration (HGB), prostate weight (PW), postvoid residual (PVR), maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QOL), International Index of Erectile Function (IIEF), and other complications were analyzed and compared respectively. RESULTS: There was no statistical difference in preoperative IPSS, preoperative QOL score, preoperative PVR, preoperative Qmax, postoperative QOL score, postoperative PVR, postoperative Qmax, IPSS difference value (DV), Qmax DV, and PVR DV between the PKEP group and the TURP group (p > 0.05). OT, BL, IUT, BFT, HST, and postoperative IPSS in the PKEP group were significantly lower than that in the TURP group (p < 0.01). RTW and GRR in the PKEP group were significantly higher than that in the TURP group (p < 0.01). QOL DV in the PKEP group was higher than that in the TURP group (p < 0.05). There was statistical difference in SSC DV between the PKEP group and the TURP group (p < 0.05). There was significant statistical difference in postoperative PW, postoperative HGB, PW DV, and HGB DV between the PKEP group and the TURP group (p < 0.01). There was significant statistical difference in IPSS, QOL, PVR, and Qmax between postoperative value and preoperative value in both groups (p < 0.01). The incidence of transurethral resection syndrome, obturator nerve reflex, transient urinary incontinence, and retrograde ejaculation between the PKEP group and the TURP group has no statistical difference (p > 0.05). Capsule perforation, blood transfusion, secondary hemorrhage, bladder neck contracture, and urethral stricture in the PKEP group were lower than that in the TURP group (p < 0.05). Bladder spasm in the PKEP group was significantly lower than that in the TURP group (p < 0.01). There was no statistical difference in preoperative and postoperative IIEF-5, effective erectile frequency, telotism average tension, sustainable telotism average time, and sexual dissatisfaction between the PKEP group and the TURP group (p > 0.05). CONCLUSIONS: PKEP and TURP have similar clinical efficacy in the treatment of massive BPH. PKEP has advantages in shorter OT, less BL, more GRR, and fewer complications, but the long-term therapeutic effect of PKEP needs further follow-up.

Pan-cancer clinical and molecular analysis of racial disparities.

BACKGROUND: Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan-cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients. METHODS: Cross-platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry. RESULTS: In the primary pan-cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR-15a, miR-17, miR-130-3p, miR-181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas. CONCLUSIONS: The current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.

Efficacy of urination in alleviating man's urethral pain associated with flexible cystoscopy: a single-center randomized trial.

BACKGROUND: This study aimed to assess whether urethral pain can be alleviated by urination in male patients undergoing flexible cystoscopy. METHODS: Ninety-six male outpatients undergoing flexible cystoscopy were randomly divided into two groups. Patients in the test group urinated during flexible cystoscopy, whilst patients in the control group received no instructions to do so. All patients received 10 mL of 2% lidocaine gel prior to assessment. Using 0 (no-pain) to 10 (unbearable severe pain) pain scores (VAS), we assessed patient discomfort prior to anesthesia gel perfusion (baseline), during gel perfusion, during cystoscope insertion through the urethra, and 15 min post-examination analysis. The entire protocol was completed by a single doctor in our Department of Urology. RESULTS: The groups showed no statistical differences regarding age or examination time. During cystoscope insertion, the test group recorded significantly lower pain scores 2 (IQR 1-3) - compared to the control group 3 (IQR 2-3), (P = 0.001). No significant differences between other evaluation points were observed between groups. CONCLUSION: Urethral pain can be significantly alleviated by urination in male patients undergoing flexible cystoscopy through the urethra. TRIAL REGISTRATION: Registry name: Clinical study of urination action to relieve urethral pain associated with flexible cystoscopy. Registration number: ChiCTR-INR-17013294 Date of Registration: 2017-11-08.

New-onset metabolic risk factors and the incidence of kidney stones: a prospective cohort study.

OBJECTIVE: To examine the association of kidney stones with new-onset hypertension, diabetes and obesity. PARTICIPANTS AND METHODS: This prospective cohort study included participants in the Qingdao Port Cardiovascular Health Study who were aged ≥18 years and had abdominal ultrasonography results in 2013 that were negative for kidney stones. Multivariable Cox regression models with time-dependent covariates were used to estimate the effects of new-onset hypertension, diabetes and obesity on the incidence of kidney stones. RESULTS: There were 9667 participants without kidney stones in 2013 (mean age 46.2 years; 75.6% men). During a mean (range) follow-up of 33.5 (6-42) months, 676 (7.0%) incident cases of kidney stones were identified. Kidney stones were more frequent among those who had new-onset of a metabolic factor vs those who did not (hypertension: 7.7 vs 6.0%; diabetes: 8.4 vs 6.6%; obesity: 7.4 vs 6.8%). Adjusted Cox models identified that increased risk of kidney stones was associated with new-onset hypertension (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.25-2.27), new-onset diabetes (HR 1.78, 95% CI 1.07-2.96), and new-onset obesity (HR 1.78, 95% CI 1.15-2.74). CONCLUSIONS: New-onset of hypertension, diabetes and obesity were all strongly associated with an increased risk of kidney stones in this prospective cohort study. Results suggest that a substantial proportion of kidney stones are potentially preventable by appropriate control of these metabolic risk factors.

Integrated genomic characterization of endometrial carcinoma.

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Ultrasonography Can Replace CT Scans as the Initial Imaging Examination of Ureteral Calculi.

OBJECTIVE: To study the feasibility of ultrasonography (US) as a replacement for CT during the diagnosis of ureteral calculi (UC). MATERIALS AND METHODS: Clinical and imaging data of patients with UC between January 2013 and December 2017 were retrospectively analyzed. According to the imaging method, patients were divided into 3 groups: Group A, CT alone; Group B, CT and US, Group C, US alone. Age, location, and the size of stones were compared among the groups. According to the maximum diameter (MD) measured by using CT in Group B, patients were subdivided into 3 groups (subgroup 1-3): MD <0.5 cm, 0.5 cm ≤ MD ≤1.0 cm, and MD >1.0 cm. The MD measured by US and CT were compared in the subgroups. RESULTS: A total of 1,289 patients with UC were admitted. The use of CT correlated with age (p = 0.000) and stone location (p = 0.004). The sensitivity and specificity of US were 71.3 and 100%. Positive US results correlated with stone size (p = 0.008), but not location (p = 0.861). The mean MDs of the calculi measured by US and CT: in subgroup 1:  0.80 ± 0.31 and 0.35 ± 0.05 cm (p = 0.000); in subgroup 2: 0.94 ± 0.32 and 0.72 ± 0.16 cm (p = 0.000); in subgroup 3: 1.75 ± 0.68 and 1.59 ± 0.52 cm (p = 0.094). CONCLUSIONS: US confirmed that UC do not require confirmatory CT. US can replace CT as the initial imaging examination of UC.

[Developing spectrum-toxicity relationship with rough set theory for hepatotoxicity material basis of Polygonum multiflorum].

Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.

Clinical significance of FBXO17 gene expression in high-grade glioma.

BACKGROUND: High-grade gliomas (HGGs) exhibit marked heterogeneity in clinical behavior. The purpose of this study was to identify a novel biomarker that predicts patient outcome, which is helpful in HGG patient management. METHODS: We analyzed gene expression profiles of 833 HGG cases, representing the largest patient population ever reported. Using the data set from the Cancer Genome Atlas (TCGA) and random partitioning approach, we performed Cox proportional hazards model analysis to identify novel prognostic mRNAs in HGG. The predictive capability was further assessed via multivariate analysis and validated in 4 additional data sets. The Kaplan-Meier method was used to evaluate survival difference between dichotomic groups of patients. Correlation of gene expression and DNA methylation was evaluated via Student's t-test. RESULTS: Patients with elevated FBXO17 expression had a significantly shorter overall survival (OS) (P = 0.0011). After adjustment by IDH1 mutation, sex, and patient age, FBXO17 gene expression was significantly associated with OS (HR = 1.29, 95% CI =1.04-1.59, P = 0.018). In addition, FBXO17 expression can significantly distinguish patients by OS not only among patients who received temozolomide chemotherapy (HR 1.35, 95% CI =1.12-1.64, P = 0.002) but also among those who did not (HR = 1.48, 95% CI =1.20-1.82, P < 0.0001). The significant association of FBXO17 gene expression with OS was further validated in four external data sets. We further found that FBXO17 endogenous expression is significantly contributable from its promoter methylation. CONCLUSION: Epigenetically modulated FBXO17 has a potential as a stratification factor for clinical decision-making in HGG.