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PURPOSEThis systematic review and meta-analysis of conventional enhanced magnetic resonance imaging (MRI) were conducted to evaluate the diagnostic performance of imaging features of microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).METHODSRelevant studies on diagnosing MVI in HCC by MRI were searched in the MEDLINE, PUBMED, EMBASE, Cochrane library, and Web of Science databases. The pooled mean sensitivity and specificity were calculated using a random effects model. The corresponding positive likelihood ratio (PLR), negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was used to summarize the overall diagnostic accuracy. Diagnostic performance was evaluated by determining the area under the curve (AUC). Regression analysis by subgroup and sensitivity analysis were used to explore potential sources of heterogeneity.RESULTSA total of 19 studies comprising 1920 HCC patients with 2033 tumors were ultimately enrolled. For the signs of the presence of peritumoral enhancement in the arterial phase, peritumoral hypointensity in the hepatobiliary phase, irregular non-smooth margin, and rim-like enhancement in the arterial phase, the pooled sensitivity values, the pooled specificity values, the pooled PLR values, the pooled NLR values, the pooled DOR values, and the values of the AUC of SROC curves were determined.CONCLUSIONThe conventional MRI features for predicting MVI showed poor diagnostic performance in HCC. Only signs of the presence of peritumoral enhancement in the arterial phase showed a moderate diagnostic accuracy.

Regulated Cell Death (RCD) is a mode of cell death that occurs through drug or genetic intervention. The regulation of RCDs is one of the significant reasons for the long survival time of tumor cells and poor prognosis of patients. Long non-coding RNAs (lncRNAs) which are involved in the regulation of tumor biological processes, including RCDs occurring on tumor cells, are closely related to tumor progression. In this review, we describe the mechanisms of eight different RCDs which contain apoptosis, necroptosis, pyroptosis, NETosis, entosis, ferroptosis, autosis and cuproptosis. Meanwhile, their respective roles in the tumor are aggregated. In addition, we outline the literature that is related to the regulatory relationships between lncRNAs and RCDs in tumor cells, which is expected to provide new ideas for tumor diagnosis and treatment.

Cancer stem cells (CSCs) are considered to be a kind of tumor cell population characterized by self-renewal, easy to metastasize and drug resistance, which play an indispensable role in the occurrence, development, metastasis and drug resistance of tumors, and their existence is an important reason for high metastasis and recurrence of tumors. Long non-coding RNAs (LncRNAs), which are more than 200 nucleotides in length, have a close relationship with the malignant progression of cancer.In recent years, abundant studies have reavling that LncRNAs are beneficial to the regulation of various cancer stem cells. Linc-ROR, as a newly discovered intergenic non-protein-coding RNA in recent years, is considered to be a key regulator affecting the development of human tumors. Dysregulation of Linc-ROR is related to stemness phenotype and functional regulation of cancer stem cells. For that, Linc-ROR has the potential to be used as a diagnostic biomarker for cancer patients and can serve as a clinically meaningful potential therapeutic target. In this review, we generalize the existing research results on the important role of Linc-ROR in regulation of CSCs.

The tumor microenvironment (TME) profoundly influences tumor progression and affects immunotherapy responses and resistance. Understanding its heterogeneity is the key for developing immunotherapy. However, the available methods can only partially portray the TME heterogeneity with a small number of cell types. Here, we developed a deep learning-based frame with a design visible, DCNet, that embeds the relationships between cells and their marker genes in the neural network, and can infer the cell landscape with more than 400 cell types based on bulk RNA-seq data. DCNet accurately recapitulated the cell landscape of multiple single cell RNA-seq datasets, which showed better robustness and stability. Based on the cell landscape of TCGA patients, which was built with DCNet, the patients were divided into two groups with significant differences in survival time and distinct cell-type populations. DCNet provides a foundation for decoding TME heterogeneity. The source code of DCNet can be found on GitHub: https://github.com/xindd/DCNet.

BackgroundTinnitus can interfere with a patient’s speech discrimination, but whether tinnitus itself or the accompanying sensorineural hearing loss (SNHL) causes this interference is still unclear. We analyzed event-related electroencephalograms (EEGs) to observe auditory-related brain function and explore the possible effects of SNHL on auditory processing in tinnitus patients.MethodsSpeech discrimination scores (SDSs) were recorded in 21 healthy control subjects, 24 tinnitus patients, 24 SNHL patients, and 27 patients with both SNHL and tinnitus. EEGs were collected under an oddball paradigm. Then, the mismatch negativity (MMN) amplitude and latency, the clustering coefficient and average path length of the whole network in the tinnitus and SNHL groups were compared with those in the control group. Additionally, we analyzed the intergroup differences in functional connectivity among the primary auditory cortex (AC), parahippocampal gyrus (PHG), and inferior frontal gyrus (IFG).ResultsSNHL patients with or without tinnitus had lower SDSs than the control subjects. Compared with control subjects, tinnitus patients with or without SNHL had decreased MMN amplitudes, and SNHL patients had longer MMN latencies. Tinnitus patients without SNHL had a smaller clustering coefficient and a longer whole-brain average path length than the control subjects. SNHL patients with or without tinnitus had a smaller clustering coefficient and a longer average path length than patients with tinnitus alone. The connectivity strength from the AC to the PHG and IFG was lower on the affected side in tinnitus patients than that in control subjects; the connectivity strength from the PHG to the IFG was also lower on the affected side in tinnitus patients than that in control subjects. However, the connectivity strength from the IFG to the AC was stronger in tinnitus patients than that in the control subjects. In SNHL patients with or without tinnitus, these changes were magnified.ConclusionChanges in auditory processing in tinnitus patients do not influence SDSs. Instead, SNHL might cause the activity of the AC, PHG and IFG to change, resulting in impaired speech recognition in tinnitus patients with SNHL.

Abstract Acute lymphoblastic leukemia (ALL) with granular blasts was historically referred to as “granular ALL”, but this is not recognized as a distinct entity in the current WHO classification. This rare morphological feature is predominantly associated with a B-cell immunophenotype, while T-ALL with prominent cytoplasmic granules is extremely rare, with limited available genetic, molecular, and prognostic data. Here, we report a unique case of ALL in a 9-year-old girl. Initial blood tests revealed leukocytosis, and both peripheral blood and bone marrow morphology showed a high number of blasts with granular cytoplasm and bilobed nuclei. Immunophenotyping confirmed T-cell origin. The patient tested positive for KMT2A::AFDN, with WT1 overexpression, and NRAS and EZH2 mutations were detected by next-generation sequencing (NGS). Remarkably, the patient achieved complete remission after treatment and has shown no signs of relapse for nearly four years. Her favorable response to conventional therapy underscores the importance of molecular phenotyping in the treatment of this disease. The continued use of NGS to gather relevant molecular data is crucial for further understanding the molecular phenotype and prognosis of such atypical ALL cases.

Aim: To investigate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma (ICC) after resection. Methods: Studies were systematically searched until August 2021 in the following databases: MEDLINE, EMBASE, PUBMED, Web of Science, Cochrane Library, Science Direct, and Springer Link. Overall survival (OS) and recurrence-free survival (RFS) were considered as the main outcomes. Pooled hazard ratio (HR) with 95% confidence interval (95%CI) was reported as results for the survival data. Subgroup analysis was conducted on the outcomes stratified by early-stage ICC and intra-arterial chemotherapeutic regimen. Results: Eleven studies with 2,757 patients were finally included in the study. The pooled HR of OS was 0.68 (95%CI: 0.50-0.87, I²=83.7%). The pooled HR of RFS was 1.00 (95%CI: 0.69-1.31, I²=88%). Receipt of postoperative adjuvant TACE improved the OS in the early-stage ICC subgroup (HR=0.68, 95%CI: 0.50-0.86, I²=54%). Addition of carboplatin could slightly improve the OS (HR=0.6, 95%CI: 0.35-0.85, I²=48%). But receipt of postoperative adjuvant TACE (HR=1.06, 95%CI: 0.83-1.29, I²=41.2%) or use of carboplatin (HR=1.30, 95%CI: 0.93-1.67, I²=0%) caused no significant improvement in the RFS in the early-stage ICC subgroup. Conclusions: Postoperative adjuvant TACE could improve the OS in ICC patients after hepatectomy but could not prevent late recurrence. Survival benefit was also found in early-stage ICC patients undergoing postoperative adjuvant TACE after hepatectomy. Addition or non-addition of carboplatin in chemoembolization showed a similar OS outcome. [ABSTRACT FROM AUTHOR]

Abstract Biliary tract cancer (BTC) that contains cholangiocarcinoma, gallbladder cancer, and ampullary cancer is highly malignant and mostly diagnosed in elderly patients. Over the past decades, human life has globally risen; thus, aging emerges as the primary risk factor for BTC. However, an effective treatment for this vulnerable population remains a large clinical challenge. As a result, the incidence and mortality of TBC remains high. Here, we discuss the potential link between aging and BTC from the aspects of molecular and cellular mechanisms, surgical resection, and chemotherapy. In addition, we update a number of clinical trials that are currently ongoing in elderly patients. The overview of BTC in elderly patients is expected to help develop a new therapeutic strategy tailored to this elderly population, ultimately improving their life quality.

Abstract Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy here. We conducted an integrative genomic analysis on GC and identified early drivers lead to metastasis. Whole-exome sequencing (WES), transcriptomes sequencing and targeted-exome sequencing (TES) were performed on tumors and matched normal tissues from 432 Chinese GC patients, especially the comparative analysis between higher metastatic-potential (HMP) group with T1 stage and lymph-node metastasis, and lower metastatic-potential (LMP) group without lymph-nodes or distant metastasis. HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, more immune cell infiltration than LMP group. An integrated mRNA-lncRNA signature based on differentially expressed genes was constructed and its prognostic value was better than traditional TNM stage. We identified 176 candidate prometastatic mutations by WES and selected 8 genes for following TES. Mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. We further demonstrated that mutated MADCAM1 could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages by regulating CCL2 through Akt/mTOR axis. In conclusion, GCs with different metastatic-potential are distinguishable at the genetic level and we revealed a number of potential metastatic driver mutations. Driver mutations in early-onset metastatic GC could promote metastasis by establishing an immunosuppressive microenvironment. This study provided possibility for future target therapy of GC.