Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumor types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Influenza D virus infection in China, 2022-2023.

Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.

A three miRNAs panel in paraffin tissue serves as tool for predicting prognosis of renal cell carcinoma.

Background: Renal cell carcinoma (RCC) stands as the most prevalent form of urogenital cancer. However, there is currently no universally accepted method for predicting the prognosis of RCC. MiRNA holds great potential as a prognostic biomarker for RCC. Methods: A total of 100 cases with complete paraffin specimens and over 5-year follow-up data meeting the requirements were collected. Utilizing the clinical information and follow-up data of the specimens, an information model was developed. The expression levels of eight microRNAs were identified using RT-qPCR. Finally, determine and analyze the clinical application value of these microRNAs as prognostic markers for RCC. Results: Significant differences were observed in the expression of two types of miRNAs (miR-378a-5p, miR-23a-5p) in RCC tissue, and three types of miRNAs (miR-378a-5p, miR-642a-5p, miR-23a-5p) were found to be linked to the prognosis of RCC. Establish biomarker combinations of miR-378a-5p, miR-642a-5p, and miR-23a-5p to evaluate RCC prognosis. Conclusion: The combination of three microRNA groups (miR-378a-5p, miR-642a-5p, and miR-23a-5p) identified in paraffin section specimens of RCC in this study holds significant potential as biomarkers for assessing RCC prognosis.

The value of a panel of circulating microRNAs in screening prostate cancer.

Background: Prostate cancer (PCa) remains a worldwide public health problem that poses a serious threat to the health of men worldwide. Many studies have found that microRNA (miRNA) in serum has the potential to be a biomarker for cancer screening. Our study was conducted to investigate the value of serum miRNAs in PCa screening. Methods: We selected 12 miRNAs from past studies for its association with PCa. We checked the expression levels of these miRNAs in the serum of 112 PCa patients and 112 healthy controls in a two-stage experiment. We plotted the receiver operating characteristic curve of miRNAs in the validation stage and constructed a four-miRNA panel with the highest diagnostic value using stepwise logistic regression. We also predicted the target genes with these four miRNAs through online databases and performed Gene Ontology functional annotation and pathway analysis. Results: The results showed that six miRNAs (miR-429, miR-10a-5p, miR-183-5p, miR-181a-5p, miR-1231, miR-129-5p) were abnormally expressed in the serum of PCa patients. We used four of these miRNAs including miR-1231, miR-10a-5p, miR-429 and miR-129-5p to construct a combination of miRNAs with high specificity and sensitivity in screening PCa (area under the curve =0.878). Bioinformatics analysis showed that the genes targeted by these miRNAs can be linked to the development of PCa. Conclusions: Our study detected and identified a set of miRNAs that serves as screening marker for PCa, which may assist in early diagnosis and treatment of PCa.

A serum panel of three microRNAs may serve as possible biomarkers for kidney renal clear cell carcinoma.

BACKGROUND: Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). METHODS: This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. RESULTS: We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. CONCLUSIONS: The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.

Profiling of Serum miRNAs Constructs a Diagnostic 3-miRNA Panel for Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.

The value of a three-microRNA panel in serum for prostate cancer screening.

BACKGROUND: Globally, prostate cancer is the second most common malignancy in males. Serum microRNAs (miRNAs) may function as non-invasive and innovative biomarkers for various cancers. Our study aimed to determine potential miRNAs for prostate cancer screening. METHODS: A three-stage study was accomplished to ascertain crucial miRNAs as markers. In the screening stage, we searched PubMed for aberrantly expressed miRNAs relevant to prostate cancer and selected them as candidate miRNAs. In training and validation stages, with serum specimens from 112 prostate cancer patients and 112 healthy controls, expressions of candidate miRNAs were identified through quantitative reverse transcription-polymerase chain reaction. The diagnostic capabilities of miRNAs were determined by receiver operating characteristic curves. Bioinformatic analysis was utilized to explore the function of the critical miRNAs. RESULTS: Expression of six serum miRNAs (miR-34b-3p, miR-556-5p, miR-200c-3p, miR-361-5p, miR-369-3p, miR-485-3p) were significantly altered in prostate cancer patients contrasted with healthy controls. The optimal combination of critical miRNAs is a three-miRNA panel (miR-34b-3p, miR-200c-3p, and miR-361-5p) with good diagnostic capability. FLRT2, KIAA1755, LDB3, and NTRK3 were identified as the potential genes targeted by the three-miRNA panel. CONCLUSIONS: The three-miRNA panel may perform as an innovative and promising serum marker for prostate cancer screening.

Radiofrequency ablation combined with toripalimab for recurrent hepatocellular carcinoma: A prospective controlled trial.

OBJECTIVE: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti-PD-1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. METHODS: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow-up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi-square tests, Kaplan-Meier, and Cox proportional hazards models were utilized to analyze the data. RESULTS: The median follow-up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti-PD-1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child-Pugh grade A (HR: 0.38, p = 0.032). CONCLUSIONS: Combining RFA with anti-PD-1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.

The Importance of Expert Knowledge for Automatic Modulation Open Set Recognition.

Automatic modulation classification (AMC) is an important technology for the monitoring, management, and control of communication systems. In recent years, machine learning approaches are becoming popular to improve the effectiveness of AMC for radio signals. However, the automatic modulation open-set recognition (AMOSR) scheme that aims to identify the known modulation types and recognize the unknown modulation signals is not well studied. Therefore, in this paper, we propose a novel multi-modal marginal prototype framework for radio frequency (RF) signals (MMPRF) to improve AMOSR performance. First, MMPRF addresses the problem of simultaneous recognition of closed and open sets by partitioning the feature space in the way of one versus other and marginal restrictions. Second, we exploit the wireless signal domain knowledge to extract a series of signal-related features to enhance the AMOSR capability. In addition, we propose a GAN-based unknown sample generation strategy to allow the model to understand the unknown world. Finally, we conduct extensive experiments on several publicly available radio modulation data, and experimental results show that our proposed MMPRF outperforms the state-of-the-art AMOSR methods.

Metal-immobilizing Pseudomonas taiwanensis WRS8 reduces heavy metal accumulation in Coriandrum sativum by changing the metal immobilization-related bacterial population abundances.

Metal-immobilizing bacteria play a critical role in metal accumulation in vegetables. However, little is known concerning the mechanisms involved in bacteria-induced reduced metal availability and uptake in vegetables. In this study, the impacts of metal-immobilizing Pseudomonas taiwanensis WRS8 on the plant biomass, Cd and Pb availability and uptake in two coriander (Coriandrum sativum L.) cultivars, and bacterial community structure were investigated in the polluted soil. Strain WRS8 increased the biomass of two coriander cultivars by 25-48% and reduced Cd and Pb contents in the edible tissues by 40-59% and available Cd and Pb contents in the rhizosphere soils by 11.1-15.2%, compared with the controls. Strain WRS8 significantly increased the pH values and relative abundances of the dominant populations of Sphingomonas, Pseudomonas, Gaiellales, Streptomyces, Frankiales, Bradyrhizobium, and Luteimonas, while strain WRS8 significantly decreased the relative abundances of the dominant populations of Gemmatimonadaceae, Nitrospira, Haliangium, Paenibacillus, Massilia, Bryobacter, and Rokubacteriales and the rare bacterial populations of Enterorhabdus, Roseburia, Luteibacter, and Planifilum in the rhizosphere soils, compared with the controls. Significantly negative correlations were observed between the available metal concentrations and the abundances of Pseudomonas, Luteimonas, Frankiales, and Planifilum. These results implied that strain WRS8 could affect the abundances of the dominant and rare bacterial populations involved in metal immobilization, resulting in increased pH values and decreased metal availability and uptake in the vegetables in the contaminated soil.

Current status and prospect of treatments for recurrent hepatocellular carcinoma.

Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.

Bladder cancer diagnosis with a four-miRNA panel in serum.

Background: Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. Materials & methods: A total of 224 participants were involved in this three-cohort trial. A total of 15 candidate miRNAs were selected, and miRNAs with diagnostic ability were screened out with quantitative reverse transcription PCR. Diagnostic capability was ascertained by the receiver operating characteristic curve and area under the curve. Bioinformatics analysis was constructed for target gene prediction and functional annotation. Results: Six candidate miRNAs showed significantly different expression between bladder cancer patients and normal controls, and the final diagnostic panel comprised miR-181b-5p, miR-183-5p, miR-199-5p and miR-221-3p. Conclusion: This four-miRNA panel could represent a stable biomarker for bladder cancer diagnosis.

Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. After an experiment composed of 224 participants, the authors screened out six candidate miRNAs that may contribute to diagnosing bladder cancer. The authors also repeatedly verified the reliability of candidate miRNAs. Finally, a combination of multiple miRNAs, consisting of miR-181b-5p, miR-183-5p, miR-199-5p, and miR-221-3p, was better and more reliable in predicting bladder cancer occurrence.

Identification of D/Yama2019 Lineage-Like Influenza D Virus in Chinese Cattle.

Outbreaks of influenza D virus (IDV) continue to be reported in many countries. On the basis of the hemagglutinin-esterase fusion (HEF) gene, five IDV genetic lineages have been identified: D/OK, D/660, D/Yama2016, D/Yama2019 and D/CA2019 lineages. Previously reported IDV strains in China all form a sub-clade (D/China sub-lineage) within D/OK lineage. From October 2021 to February 2022, nasal swab samples (n = 250) were collected from apparently healthy cattle in slaughterhouses around the city of Guangzhou, China, and screened for IDV by RT-PCR. Ten samples were positive for IDV. An IDV strain with nearly complete genome sequences was identified and designated as D/bovine/CHN/JY3001/2021. Importantly, sequence alignments and phylogenetic analyses revealed that this IDV strain is genetically close to the strains (>98% homology) in the D/Yama2019 lineage that has been found only in Japan, but distant from the previously reported Chinese IDV strains (~95% similarity). These results demonstrate the emergence of D/Yama2019 lineage IDV in Chinese cattle herds, highlighting a need for future surveillance of D/Yama2019-like viruses toward better understanding both epidemiology and diversity of IDV in China.

A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) has been a major health problem and is one of the most malignant tumors around the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The aim of this study was to explore serum miRNAs as potential biomarkers for screening RCC. Methods: A three-phase study was conducted to explore serum miRNAs as potential biomarkers for screening RCC. In the screening phase, 12 candidate miRNAs related to RCC were selected for further study by the ENCORI database with 517 RCC patients and 71 NCs. A total of 220 participants [108 RCC patients and 112 normal controls (NCs)] were enrolled for training and validation. The dysregulated candidate miRNAs were further confirmed with 30 RCC patients and 30 NCs in the training phase and with 78 RCC patients and 82 NCs in the validation phase. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used for assessing the diagnostic value of miRNAs. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, six miRNAs (miR-18a-5p, miR-138-5p, miR-141-3p, miR-181b-5p, miR-200a-3p, and miR-363-3p) in serum were significantly dysregulated in RCC patients. A four-miRNA panel was built by combining these candidate miRNAs to improve the diagnostic value with AUC = 0.908. ABCG1 and RNASET2, considered potential target genes of the four-miRNA panel, may play a significant role in the development of RCC. Conclusion: A four-miRNA panel in serum was identified for RCC screening in our study. The four--miRNA panel has a great potential to be a non-invasive biomarker for RCC screening.

A four-miRNA signature in serum as a biomarker for bladder cancer diagnosis.

BACKGROUND: Urinary bladder cancer (BCa) is globally the 10th most frequent cancer. As a novel diagnostic tool, miRNA in serum screening is non-invasive. This project aimed to determine particular serum miRNAs as novel biomarkers for diagnosing urinary BCa. METHODS: We designed a three-phase study with 122 healthy controls (HCs) and 132 BCa patients. The 30 miRNAs' expressions in serum from HCs and BCa patients were detected during the screening phase. The miRNAs with the most dysregulation were tested in the training (HCs vs. BCa, 30 each) and validation (80 HCs vs. 82 BCa) phase further. The diagnostic ability of these candidate miRNAs was estimated by the receiver operating characteristic (ROC) curves as well as the area under the ROC curve (AUC). The miRNAs' target genes and their annotations to functions were predicted utilizing bioinformatic assays. RESULTS: Six serum miRNAs (miR-124-3p, miR-182-5p, miR-1-3p, miR-196a-5p, miR-23b-3p and miR-34a-5p) had significantly different expression between BCa patients and HCs in the training and validation phase. The four-microRNA panel improved the diagnostic value, with AUC =0.985. The result of bioinformatic analysis showed that these miRNAs' target genes in the panel may be related to the MAPK signaling pathway in bladder cancer. CONCLUSIONS: Our study identified a four-miRNA panel that is a non-invasive new biomarker for diagnosing BCa.

Integrative immunogenomic analysis reveals transcriptional and immune-related differences in hepatocellular carcinoma patients with different disease-free survival.

A comprehensive investigation of the neoantigen spectrum and immune infiltration in patients with hepatocellular carcinoma (HCC) is lacking. This study aimed to examine the molecular features correlating with better prognoses in HCC patients. 27 paired tumor and normal tissues from 27 HCC patients were collected and performed with whole-exome sequencing. The most frequently mutated gene in 27 HCC patients was TP53 (16/27, 59.26%). Based on the whole median disease-free survival (DFS), all patients were divided into 'long-term' (n = 14, median DFS = 318 weeks) and 'short-term' (n = 13, median DFS = 11 weeks) groups. RNA-seq was performed to compare differentially expressed genes, immune infiltration, and neoantigens. Immunohistochemistry was performed to evaluate the immune infiltration. There were no significant differences in tumor mutation burden, immune score, cytolytic activity score, or neoantigen load between two groups. Compared with the long-term group, significantly increased B lineage (P = 0.0463), myeloid dendritic cells (P = 0.0152), and fibroblast (P = 0.0244) infiltration levels were observed in the short-term group, in which genes involved in ribosome, proteasome, and ECM-receptor interaction pathways were also overexpressed. Additionally, 16 patients with tumor thrombus were explored to identify specific biomarkers for prognosis. We found that patients with tumor thrombus carrying TP53/ARID2 neoantigens had significantly longer DFS. In conclusion, higher B lineage, myeloid dendritic cells, and fibroblast infiltration levels might cause poor prognosis in the short-term group, which also showed higher expression of genes involved in ribosome, proteasome, and ECM-receptor interaction pathways. In patients with tumor thrombus, specific TP53/ARID2 neoantigens may be used as biomarkers toward personalized immunotherapy.

Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety.

PURPOSE: This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan-Meier curves, while Cox analysis was used to identify factors affecting the prognosis. RESULTS: The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0 months and 8.0 months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient. CONCLUSIONS: DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival.

DEB-TACE with irinotecan versus C-TACE for unresectable intrahepatic cholangiocarcinoma: a prospective clinical study.

Objectives: DEB-TACE with irinotecan and C-TACE were compared with regards to safety and efficacy for the therapy of intrahepatic cholangiocarcinoma (ICC). Methods: Institutional Review Board approved our trial and we registered it in the Chinese Clinical Trial Registry (ChiCTR1900022856). Forty patients with biopsy-confirmed ICC were randomised to either receive DEB-TACE or C-TACE treatment with 20 patients in each treatment arm. The primary endpoints objective response rate (ORR) and progression free survival (PFS) using the mRECIST to evaluate the tumours. The secondary endpoints were overall survival (OS) and safety. The chi-square was used to analyse the data. The Kaplan-Meier method and Cox analysis were used to evaluate the survival data. Results: ORR (70% in DEB-TACE group vs. 20% in C-TACE, p = .001) at 1 month after therapy, ORR (50% vs. 15%, p = .018) at 3 months and DCR (70% vs. 30%, p = .011) at 6 months, while no difference was found in other groups. (all p > .05) The median PFS with DEB-TACE was longer than that with C-TACE (8.0 months vs. 3.0 months) (p = .042). Although the median OS was longer with DEB-TACE than with C-TACE (11.5 months vs. 9.0 months), the difference was not statistically significant (p = .280). The Cox regression analysis demonstrated that TACE sessions (p = .017) and low CA125 levels (p = .001) were independent favourable prognostic factors. The most frequent adverse event was elevated transaminase levels (20/20 in DEB-TACE group vs. 15/20 in C-TACE group) (p = .047). Conclusion: Our prospective study suggested better ORR and PFS with DEB-TACE with irinotecan as compared to C-TACE with irinotecan in the treatment of unresectable ICC.

A four-microRNA panel in serum may serve as potential biomarker for renal cell carcinoma diagnosis.

Background: Renal cell carcinoma (RCC) is one out of the most universal malignant tumors globally, and its incidence is increasing annually. MicroRNA (miRNA) in serum could be considered as a non-invasive detecting biomarker for RCC diagnosis. Method: A total of 224 participants (112 RCC patients (RCCs) and 112 normal controls (NCs)) were enrolled in the three-phrase study. Reverse transcription quantitative PCR (RT-qPCR) was applied to reveal the miRNA expression levels in RCCs and NCs. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to predict the diagnostic ability of serum miRNAs for RCC. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, the expression degree of miR-155-5p, miR-224-5p in serum was significantly upregulated in RCC patients, and miR-1-3p, miR-124-3p, miR-129-5p, and miR-200b-3p were downregulated. A four-miRNA panel was construed, and the AUC of the panel was 0.903 (95% CI: 0.847-0.944; p < 0.001; sensitivity = 75.61%, specificity = 93.67%). Results from GEPIA database indicated that CHL1, MPP5, and SORT1 could be seen as promising target genes of the four-miRNA panel. Survival analysis of candidate miRNAs manifested that miR-155-5p was associated with the survival rate of RCC significantly. Conclusions: The four-miRNA panel in serum has a great potential to be non-invasive biomarkers for RCC sift to check.

Are the Derived Indexes of Peripheral Whole Blood Cell Counts (NLR, PLR, LMR/MLR) Clinically Significant Prognostic Biomarkers in Multiple Myeloma? A Systematic Review And Meta-Analysis.

BACKGROUND: Multiple myeloma (MM) is an incurable malignant plasma cell tumor. Whole blood cell count (WBCC) derived indexes are widely used as a predictive biomarker for various types of solid and hematological malignant tumors. Our study is to evaluate its effectiveness in MM by meta-analysis. METHODS: Relevant literatures were retrieved from PubMed, Embase and Web of Science databases according to PRISMA guideline. All relevant parameters were extracted and combined for statistical analysis. RESULTS: Nineteen studies incorporating 3818 MM patients were eventually included in this meta-analysis. 13 studies evaluated that elevated NLR was significantly associated with poor survival outcomes (OS: HR=2.04, P<0.001; PFS: HR=1.96, P=0.003). Elevated NLR was revealed to correlate with ISS stage (ISS III VS I-II, OR=2.23, P=0.003). A total of 7 studies have shown that elevated LMR predicts a better prognosis in MM patients (OS: HR=0.57, P<0.001; PFS: HR=0.49, P<0.05), and two other studies demonstrated that increased MLR was related to poor OS/PFS (OS: HR=1.58, P<0.05; PFS: HR=1.60, P<0.05). However, in the other 6 studies including 1560 patients, the prognostic value of PLR had not been confirmed (OS: HR=0.89, P>0.05; PFS: HR=0.87, P>0.05). CONCLUSIONS: The indexes NLR and LMR/MLR derived from WBCC were validated to be useful biomarkers to predict the prognosis in MM patients, but the evidence of PLR was insufficient.