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Background: Spontaneous tumor rupture is a rare and life-threatening complication of hepatocellular carcinoma (HCC). The best treatment strategy remains unclear.Methods: The clinical data of 137 patients with spontaneously ruptured HCC from 2010 to 2015 were reviewed retrospectively. We investigated the outcome and prognostic factors of various treatment strategies.Results: Of the 137 patients, 53, 45, 3, and 36 patients underwent transcatheter arterial chemoembolization (TACE) alone, liver resection (LR) (LR alone or TACE + LR), surgical hemostasis, and conservative therapy. The patients undergoing LR had longest overall survival (OS). In the TACE alone group, independent factors affecting 30-day mortality were MELD score ≥ 12, AFP ≥ 1000 ng/ml, and largest tumor size ≥ 10 cm. AFP ≥ 1000 ng/ml, largest tumor size ≥ 10 cm, and no tumor capsule were significantly associated with poorer OS. In the LR group, largest tumor size ≥ 10 cm and no tumor capsule were the only independent prognostic factors for poorer OS and recurrence-free survival (RFS). Hypovolemic shock was an independent prognostic factor for poorer OS. The differences in OS between the TACE + LR group and LR alone group were not significant (P = 0.955). However, the RFS is significantly better in the LR alone group than those in the TACE + LR group (P = 0.031).Conclusion: For resectable tumor, LR is the treatment of choice for patients with spontaneous ruptured HCC and preserved liver function. The delay in LR due to preoperative TACE may account for its worse RFS compared with LR alone. In patients with an unresectable tumor, TACE therapy alone improved survival over conservative therapy. [ABSTRACT FROM AUTHOR]

Abstract Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many biological processes, such as cancer development and progression. Specifically, TP73-AS1, a novel cancer-related lncRNA, was documented to be up-regulated in several malignancies, but the clinical significance and functional role of TP73-AS1 in GC is still unknown. RT-qPCR was performed to evaluate TP73-AS1 transcription in GC tissue specimens and cell lines. In addition, the correlation between TP73-AS1 transcription and clinicopathologic features was further evaluated. Moreover, the effects of TP73-AS1 on GC cell were measured in vitro and in vivo. The data documented that TP73-AS1 was enhanced in GC tissues and cells, and TP73-AS1 transcription level was tightly associated with tumor size, TNM stage, and overall survival in 76 GC patients. What's more, decreased TP73-AS1 could restrain cell growth and colony-forming capacity and promoted apoptosis partly by regulating Bcl-2/caspase-3 pathway. Importantly, TP73-AS1 could promote xenograft growth in vivo. Silencing of TP73-AS1 inhibited GC cell migratory and invasive properties partly by reversing snail-mediated epithelial-to-mesenchymal transition (EMT). Collectively, this study may help to develop the treatment strategy for GC. Highlights • TP73-AS1 is upregulated in gastric cancer tissue samples and cell lines. • TP73-AS1 expression is correlated with depth of invasion, TNM stage and overall survival of GC patients. • TP73-AS1 facilitates GC cell growth in vitro and in vivo. • TP73-AS1 protects against apoptosis partly via regulating Bcl-2/caspase-3 pathway. • Silenced TP73-AS1 inhibits GC cell metastatic properties partly by reversing EMT. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have demonstrated that aberrant Kif2a expression is associated with tumor aggressiveness and poor prognosis in various human cancers. However, the clinicopathological significance of Kif2a in laryngeal squamous cell carcinoma (LSCC) is unknown. The aim of this study is to analyze the prognostic significance of Kif2a, alone and in combination with Ki67 protein expression, in LSCC patients.Methods: We examined the expression status of Kif2a and Ki67 protein in 165 laryngeal tissues (137 primary tumors and 28 cases of matched normal surgical margins) by immunohistochemistry (IHC) analysis using tissue microarrays.Results: We found that expression correlated with clinical parameters and overall survival (OS). Our results revealed that Kif2a and Ki67 protein expression was significantly higher in cancerous tissues compared to normal surgical margins. High Kif2a protein expression (Kif2a+) was significantly associated with tumor stage (P=0.026) and cervical lymph node metastasis (P=0.034). A significant correlation between Kif2a and Ki67 protein expression was observed (P=0.040). Multivariate analysis revealed that patients with Kif2a+ (hazard ratio [HR] 3.640, 95% confidence interval [CI] 1.253-10.570; P=0.018) and high Ki67 (Ki67+) expression (HR 3.086, 95%CI 1.016-9.371; P=0.047) had poor OS.Conclusion: We speculate that Kif2a and Ki67 can be used as prognostic markers for LSCC patients. [ABSTRACT FROM AUTHOR]

This study aimed to retrospectively evaluate a large Chinese cohort's baseline characters and develop a new predictive scoring system. Methods: A total of 491 FL patients were reviewed, and 337newly diagnosed 1–3a FL patients from January 2010 to October 2020 were enrolled in our retrospective cohort. Results: Progression-free survival (PFS) was assessed as the first endpoint; the 2-year and 5-year PFS were 81.4% and 67.8%, respectively. A new risk scoring system (SLMR) was established after the univariable and multivariable analyses, and four independent factors such as β2-MG, LDH, LMR, the number of nodal areas ≥ 5, and spleen involvement were detected by FDG-PET imaging were included. The SLMR was compared with the existing models using discrimination and calibration, and k-fold cross-validation was performed for internal validation. Our cohort classified patients into three groups (low-, intermediate- and high) according to the SLMR and showed the best model performance, especially for FL3a and received rituximab maintenance after induction therapy patients. • The SLMR was developed for FL patients with PFS assessed as the first endpoint, including spleen involvement, LMR, the number of nodal areas ≥5, β2-MG, and LDH. • FL3a and FL1-2 patients both gain benefits from receiving rituximab maintenance after achieving remission. • The SLMR appears to perform better than traditional models in our cohort, especially for FL3a and received rituximab maintenance patients. [ABSTRACT FROM AUTHOR]

Abstract: Some but not all patients with Tolosa–Hunt syndrome (THS) have dramatic responses to steroid treatment. A systematic study about the factors that may influence the steroid response of THS patients has not been published. We retrospectively identified 40 patients diagnosed with THS and treated with steroids with respect to patient age at onset, gender, the cranial nerve(s) involved, as well as imaging findings and laboratory tests. Within the context of these data we evaluated the therapeutic efficacy of steroid treatment and recurrence of attacks. We did not note a significant relationship between genders, whether THS was benign or inflammatory, the distribution of cranial nerve palsies, the initial dose of steroids and the effectiveness of steroid treatment for relief of orbital pain or cranial nerve palsies at 72h or 1week after treatment. Our study reveals that a rapid alleviation of pain by steroid treatment is a characteristic feature of THS patients. The alleviation of cranial nerve palsy is somewhat slower and more variable, and may involve additional mechanisms. There is an effect of patient age and whether attacks will recur (recurrence was more likely in patients who were young at the time of first attack), whether THS will be benign or inflammatory (more likely to be inflammatory in young patients) and the short-term response of cranial nerve palsy to steroid treatment, which was more effective in young patients. These relationships may be of value in counseling patients presenting with THS. [Copyright &y& Elsevier]

Abstract: Papillary renal cell carcinoma (PRCC) includes two different morphological subtypes. The differences of genetics and ultrastructure of the two subtypes have been rarely reported. Also, new biomarkers related to the diagnosis and prognosis of PRCC have still not been well elucidated. Immunohistochemistry, fluorescence in situ hybridization (FISH) and transmission electron microscopy were used systematically to determine the characteristics of 56 cases of PRCC and to reveal new diagnostic and prognostic information. Type 1 PRCC presented higher expression rates of EMA and CK7, whereas type 2 presented a higher expression rate of CD10. New immunohistochemical markers, including: p504s, PAX-2, PAX-8 and CA-IX showed extensive immunostaining in PRCC. We first revealed a distinct immunostaining pattern of CA-IX, which was located in multiple foci in PRCC. All tumors had at least one chromosomal aberration including loss of Y, gains of 7 or 17. Gain of chromosome 17 was common in type 1; losses of chromosome 18, 11 and 8 appeared in type 2. Ultrastructurally, glycogen granules and secondary lysosomes were seen in type 1, mitochondria and smooth endoplasmic reticulum were scattered in type 2. Tumor subtype, nuclear grade, TNM stage, clear cell renal cell carcinoma (CCRCC) component and sarcomatoid elements, metastasis, CAIX expression, losses of chromosome 18 and 8 were related to poor outcome of PRCC. We conclude that the two subtypes of PRCC originate from different renal cells, and arise from partially common genetic pathways. EMA, CK7, CD10, p504s, PAX-2, PAX-8 and CA-IX are helpful markers in the differential diagnosis of PRCC. CA-IX expression, losses of chromosome 18 and 8 are new prognostic factors of PRCC. [Copyright &y& Elsevier]

Abstract: To date, the aberrations in the DNA methylation patterns that are associated with different prognoses of G-CIMP− primary GBMs remain to be elucidated. Here, DNA methylation profiling of primary GBM tissues from 13 long-term survivors (LTS; overall survival ⩾18months) and 20 short-term survivors (STS; overall survival ⩽9months) was performed. Then G-CIMP+ samples were excluded. The differentially expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP− samples. Methylation levels of 11 CpG loci (10genes) were statistically significantly lower, and 43 CpG loci (40genes) were statistically significantly higher in the tumor tissues of LTS than those of STS G-CIMP− samples (P <0.01). Of the 43 CpG loci that were hypermethylated in LTS G-CIMP− samples, 3 CpG loci localized in the promoter of ALDH1A3. Furthermore, using an independent validation cohort containing 37 primary GBM samples without IDH1 mutation and MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter predicted a better prognosis with an accompanied low expression of ALDH1A3 protein. Taken together, our results defined prognosis-related methylation signatures systematically for the first time in G-CIMP− primary GBMs. ALDH1A3 promoter methylation conferred a favorable prognosis in G-CIMP− primary GBMs. [Copyright &y& Elsevier]

• Radiomics is to provide and combine quantitative features of medical imaging to characterize tumor phenotypes, which may contribute to oncologic classification and prediction. • Dual-region signature, derived from primary neoplasm and regional lymph node from CT images, could offer incremental prognostic value over existing single radiomics signature for predicting overall survival in patients with esophageal squamous cell cancer. • To provide a promising tool for selecting appropriate treatment strategies and improve clinical outcomes of patients with ESCC. Preoperative prognostic biomarkers to guide individualized therapy are still in demand in esophageal squamous cell cancer (ESCC). Some studies reported that radiomic analysis based on CT images has been successfully performed to predict individual survival in EC. The aim of this study was to assess whether combining radiomics features from primary tumor and regional lymph nodes predicts overall survival (OS) better than using single-region features only, and to investigate the incremental value of the dual-region radiomics signature. In this retrospective study, three radiomics signatures were built from preoperative enhanced CT in a training cohort (n = 200) using LASSO Cox model. Associations between each signature and survival was assessed on a validation cohort (n = 107). Prediction accuracy for the three signatures was compared. By constructing a clinical nomogram and a radiomics-clinical nomogram, incremental prognostic value of the radiomics signature over clinicopathological factors in OS prediction was assessed in terms of discrimination, calibration, reclassification and clinical usefulness. The dual-region radiomic signature was an independent factor, significantly associated with OS (HR: 1.869, 95% CI: 1.347, 2.592, P = 1.82e-04), which achieved better OS (C-index: 0.611) prediction either than the single-region signature (C-index:0.594-0.604). The resulted dual-region radiomics-clinical nomogram achieved the best discriminative ability in OS prediction (C-index:0.700). Compared with the clinical nomogram, the radiomics-clinical nomogram improved the calibration and classification accuracy for OS prediction with a total net reclassification improvement (NRI) of 26.9% (P =0.008) and integrated discrimination improvement (IDI) of 6.8% (P <0.001). The dual-region radiomic signature is an independent prognostic marker and outperforms single-region signature in OS for ESCC patients. Integrating the dual-region radiomics signature and clinicopathological factors improves OS prediction. [ABSTRACT FROM AUTHOR]

Intelligent data-driven system prognostic methods have been popularly developed in the recent years. Despite the promising results, most approaches assume the training and testing data are from the same operating condition. In the real industries, it is quite common that different machine entities work under different scenarios, that results in performance deteriorations of the data-driven prognostic methods. This paper proposes a transfer learning method for remaining useful life predictions using deep representation regularization. The practical and challenging scenario is investigated, where the training and testing data are from different machinery operating conditions, and no target-domain run-to-failure data is available for training. In the deep learning framework, data alignment schemes are proposed in the representation sub-space, including healthy state alignment, degradation direction alignment, degradation level regularization and degradation fusion. In this way, the life-cycle data of different machine entities across domains can follow the same degradation trace, thus achieving prognostic knowledge transfer. Extensive experiments on the aero-engine dataset validate the effectiveness of the proposed method, which offers a promising solution for industrial prognostics. • The cross-domain remaining useful life prediction problem is investigated. • A deep learning-based transfer learning method is proposed for prognostics. • The target domains only include unlabeled data at early degradation periods. • Deep representation regularization schemes are proposed for data alignments. • Experiments validate the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

The dysregulation of alternative splicing (AS) has emerged as a mechanism of acute myeloid leukemia (AML). However, the prognostic impact of AS events remains under-explored in AML. Here we report the prognostic value of AS events and associated splicing factors based on three datasets of AML patients. We defined the landscape of AS events in AML and identified 7033 AS events associated with the survival of AML patients. Based on these events, we further developed a composite 15 AS event-based prognostic signature, which was independent of the cytogenetic risk stratification and patient age, and showed a better performance than known gene expression signatures. More importantly, our new signature markedly improved the European LeukemiaNet (ELN) risk classification, indicating a broad applicability in the clinical management of AML. Furthermore, the splicing-regulatory network established the correlations between prognostic AS events and associated splicing factors. The finding was validated by CRISPR-based data, which indicated that the increased expression of RBM39 contributed to the higher exon inclusion of SETD5 and conferred a poor outcome. Together, AS events may serve as a novel assortment of prognosticators for AML and could refine the ELN risk stratification. The splicing regulatory network provides clues regarding the splicing factor-mediated mechanisms of AML. [ABSTRACT FROM AUTHOR]

eIF3a is the largest subunit of eIF3, which is a key player in all steps of translation initiation. During the past years, eIF3a is recognized as a proto-oncogene, which is an important discovery in this field. It is widely reported to be correlated with cancer occurrence, metastasis, prognosis, and therapeutic response. Recently, the mechanisms of eIF3a action in the carcinogenesis are unveiled gradually. A number of cellular, physiological, and pathological processes involving eIF3a are identified. Most importantly, it is emerging as a new potential drug target in the eIF family, and some small molecule inhibitors are being developed. Thus, we perform a critical review of recent advances in understanding eIF3a physiological and pathological functions, with specific focus on its role in cancer and anticancer drug targets. [ABSTRACT FROM AUTHOR]

Background Cluster of differentiation 47 (CD47) negatively regulates macrophage phagocytosis and is correlated with adverse survival of multiple cancers. In melanoma patients, especially in Chinese melanoma patients, its prognostic value is unclear. In this study, we aim to study the prognostic value of CD47 in a Chinse melanoma patient cohort and its immunomodulation roles in mouse model. Method 164 melanoma tissue specimens were collected. The expression of CD47 in these clinical samples was examined by immunohistochemistry staining (IHC). The correlation between CD47 expression and clinicopathological parameters was assessed by statistical analysis. Prognostic values CD47 expression were also investigated. In an animal model, effects of CD47 expression on immune infiltration were examined. Results CD47 expression was positively correlated with TNM stage, distant metastasis, and death of melanoma patients with the P value of 0.008, 0.018, and 0.032 respectively. High expression of CD47 was an independent prognostic marker of overall survival (HR = 1.563, 95% CI: 1.069–2.285) and progression free survival (HR = 1.542, 95% CI: 1.053–2.258) of Chinese melanoma patients. Conclusion In conclusion, high expression of CD47 predicted poor survival in a Chinese melanoma patient cohort and impaired antitumor immune response in the animal model. Targeting CD47 might be a novel option for melanoma patients. [ABSTRACT FROM AUTHOR]

• For the first time, established a predictive model to anticipate the cytokine storms in the acute phase of SFTS patients. • By visualizing the predictive model through a nomogram, it becomes more convenient and user-friendly. • The predictive capacity of the model was evaluated based on the outcomes of 48 cytokines in the validation cohort. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients. [ABSTRACT FROM AUTHOR]

A 90-year-old man was diagnosed with primary gastric diffuse large B-cell lymphoma (PGDLBL) by PET/CT examination, gastroscopy, biopsy and histopathological analysis at a regular physical check in April, 2016. The patient received R-CO chemotherapy (rituximab, cyclophosphamide, and vincristine) and radiotherapy subsequently, with enteral nutritional treatment through 3-cavity nasogastric tube due to development of pyloric obstruction. To satisfy patient's strong desire of eating by himself, we performed surgery of exploratory laparotomy and Roux-en-Y gastric bypass (RGB) to relieve pylorus obstruction. Postoperatively, the patient resumed oral feeding, supplemented by nasogastric tube feeding at 1350 - 1550 Kcal daily. He is now 94 years old with fairly well nutrition and normal communication. The outcome of 4 year follow-up suggests that nutritional treatment and palliative medicine are important for improving prognosis and life-quality of very elderly patients with end-stage tumors apart from the effective chemotherapy, radiotherapy, and surgery. [ABSTRACT FROM AUTHOR]

• The dynamic changes in peripheral blood lymphocyte subsets were investigated in adult patients with COVID-19. • The levels of peripheral blood lymphocyte subsets (CD3+, CD4+, and CD8+) differed significantly between patients with non-severe and severe COVID-19. • The levels of peripheral blood lymphocyte subsets (CD3+, CD4+, and CD8+) differed significantly between patients who recovered and those who died of COVID-19. • Dynamic monitoring of human immune function is one of the indicators for evaluating the severity of disease and the prognosis of COVID-19 patients. Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely. The aim of this study was to investigate the dynamic changes in peripheral blood lymphocyte subsets in adult patients with COVID-19. The electronic medical records were reviewed. Data including demographic characteristics, clinical manifestations, comorbidities, laboratory data, and radiological examinations of 435 hospitalized COVID-19 patients with a confirmed SARS-CoV-2 viral infection were extracted and analyzed retrospectively. Lymphocyte subset counts at each week after the onset of the illness were compared with those of the other weeks of illness and with those of control individuals. The various lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD16/56+) were below the normal ranges at 1 week after the onset of illness, reaching a nadir during the second week. They increased gradually during the third week and returned to normal levels in the fifth week, but were still lower than those of the healthy controls. The CD3+, CD4+, and CD8+ counts were significantly lower in patients with severe disease compared to those with non-severe disease, and in patients who died compared to those who recovered. This research indicates that the levels of peripheral blood lymphocyte subsets (CD3+, CD4+, and CD8+) are associated with disease progression and severity, and with the prognosis in patients with COVID-19. Dynamic monitoring of human immune function is one of the indicators for evaluating the severity of disease and the prognosis of COVID-19 patients, and is useful for formulating appropriate treatment strategies. [ABSTRACT FROM AUTHOR]

DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response. Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype. MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values. MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a–3p, miR-17–5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a–3p was epigenetically regulated at the constitutive level. High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential. [Display omitted] • Microarray analysis identifies 77 differentially expressed miRNAs in drug resistant EOC cells. • Epigenetic modulators impact cells' drug response and metastatic capacity. • Downregulated miR-103a, 17 and 107 are shared feature of several resistant EOC cell lines and has a prognostic value. • MiRNA-mRNA integrative analysis reveals signaling pathways involved in metastasis. • Epigenetically regulated miR-103a is involved in metastasis but not drug response. [ABSTRACT FROM AUTHOR]

• We developed Non-Contrast CT radiomics fusion model, combining ML, to predict the 6-month long-term outcomes of AIS patients receiving conventional treatment. • The prediction fusion model combined radiomics and clinical features. • NCCT GrayLevelNonUniformity and Skewness features were the top radiomics predictors of AIS outcomes. • The clinical-radiomics fusion model achieved good performance for predicting the AIS outcome. • NCCT based radiomics method could be a reliable imaging biomarker for early clinical decision-making. Accurate prediction of outcomes for patients with acute ischemic stroke (AIS) is crucial for clinical decision-making. In this study, we developed prediction models based on non-contrast computed tomography (NCCT) radiomics and clinical features to predict the modified Rankin Scale (mRS) six months after hospital discharge. A two-center retrospective cohort of 240 AIS patients receiving conventional treatment was included. Radiomics features of the infarct area were extracted from baseline NCCT scans. We applied Kruskal-Wallis (KW) test and recursive feature elimination (RFE) to select features for developing clinical, radiomics, and fusion models (with clinical data and radiomics features), using support vector machine (SVM) algorithm. The prediction performance of the models was assessed by accuracy, sensitivity, specificity, F1 score, and receiver operating characteristic (ROC) curve. Shapley Additive exPlanations (SHAP) was applied to analyze the interpretability and predictor importance of the model. A total of 1454 texture features were extracted from the NCCT images. In the test cohort, the ROC analysis showed that the radiomics model and the fusion model showed AUCs of 0.705 and 0.857, which outperformed the clinical model (0.643), with the fusion model exhibiting the best performance. Additionally, the accuracy and sensitivity of the fusion model were also the best among the models (84.8% and 93.8%, respectively). The model based on NCCT radiomics and machine learning has high predictive efficiency for the prognosis of AIS patients receiving conventional treatment, which can be used to assist early personalized clinical therapy. [ABSTRACT FROM AUTHOR]

Background: Reactive thymic hyperplasia (RTH) is seen in children and adolescents receiving chemotherapy for various malignancies. However, it is not clear why this occurs only in some patients. The aim of this study was to identify the predictors for RTH in children and adolescents receiving chemotherapy for lymphoma and to determine the effect of RTH on prognosis.Methods: We reviewed the medical records of 126 lymphoma patients (October 2007-October 2012). The patients were divided into two groups according to different criteria, i.e., age at initial diagnosis (2-12 years vs. 13-18 years); presence of thymic infiltration at baseline (yes vs. no); and receipt of mediastinal radiotherapy (yes vs. no). The Kaplan-Meier method and multivariate Cox regression model analysis were used to analyze predictors for RTH. Further, patients were divided into two groups according to the occurrence of RTH during follow-up, and Kaplan-Meier survival analysis was used to analyze the prognostic value of RTH.Results: The 2-12-year-old group had a shorter duration from the end of therapy to RTH than the 13-18-year-old group (median: 3 months vs. 16 months) and a higher rate of RTH (97.1% vs. 60.3%, P < 0.001). The lymphoma thymic non-infiltration group had a shorter duration from the end of therapy to RTH than the lymphoma infiltration group (median: 4 months vs. 22 months), and a higher rate of RTH (88.2% vs. 57.6%, P < 0.001). The non-mediastinal radiotherapy group had higher rate of RTH than the mediastinal radiotherapy group (84.7% vs. 12.5%, P < 0.001). Low age, absence of thymic infiltration by lymphoma at baseline, and absence of mediastinal radiation were predictors for RTH by multivariate Cox regression analysis (P < 0.05). The RTH group had a lower recurrence rate than the non-RTH group (13.9% vs. 40%), and a longer duration from the end of therapy to recurrence (median: 10 months vs. 5 months, P < 0.001).Conclusions: Younger age, absence of thymic infiltration by lymphoma at baseline and absence of mediastinal radiotherapy are predictors for RTH in children and adolescents. RTH may be a positive prognostic factor. [ABSTRACT FROM AUTHOR]

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells. [ABSTRACT FROM AUTHOR]

• Glycolytic genes combined with immune score could define differential prognoses of AML patients. • The Risk Score calculated by LASSO Cox model based on 6 genes (METTL7B, HTR7, ITGAX, TNNI2, SIX3 and PURG) can reliably predict the prognosis of AML patients. • Nomogram model based on Risk Score and other independent prognostic factors could also predict the prognosis and survival of AML patients. Acute myeloid leukemia (AML) is widely considered an immunoresponsive malignancy. However, potential association between glycolysis-immune related genes and AML patients' prognosis has been seldom studied. AML-related data was downloaded from TCGA and GEO databases. We grouped patients according to Glycolysis status, Immune Score and combination analysis, basing on which overlapped differentially expressed genes (DEGs) were identified. The Risk Score model was then established. The results showed that totally 142 overlapped genes were probably correlated with glycolysis-immunity in AML patients, among which 6 optimal genes were screened to construct Risk Score. High Risk Score was an independent poor prognostic factor for AML. In conclusion, we established a relatively reliable prognostic signature of AML based on glycolysis-immunity related genes, including METTL7B, HTR7, ITGAX, TNNI2, SIX3 and PURG. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the relationship between intra-abdominal infection (IAI) and sarcopenia prospectively and to construct a nomogram to identify patients at a high risk of IAI.Methods: We conducted a prospective study of 682 consecutive patients with gastric cancer who underwent radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Factors contributing to IAI were determined through univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of IAI.Results: Of the 682 patients enrolled in this study, 132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI. Logistic analysis revealed that sarcopenia, tumor size, pathological type, and multivisceral resection were independent prognostic factors for IAI. The nomogram model for IAI was able to reliably quantify the risk of IAI with a strong optimism-adjusted discrimination (concordance index, 0.736).Conclusions: Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk. [ABSTRACT FROM AUTHOR]

Activation of Wnt/β-catenin signaling played a crucial role in tumorigenesis, and β-catenin ( CTNNB1 ) overexpression has been identified in numerous solid tumors. The present study was designed to determine CTNNB1 expression and its clinical significance in Chinese de novo acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the pattern of CTNNB1 expression in 140 AML patients and 46 controls. The level of CTNNB1 transcript in AML patients was significantly up-regulated compared with controls ( P <  0.001). CTNNB1 high patients showed significantly older age than CTNNB1 low patients ( P <  0.05). The frequency of high CTNNB1 expression was significantly observed in patients with intermediate/poor karyotypes. CTNNB1 high patients had a significantly lower complete remission (CR) rate than CTNNB1 low patients ( P  = 0.004). Among cytogenetically normal AML (CN-AML), CTNNB1 high patients presented significantly shorter overall survival (OS, P  = 0.004) and leukemia-free survival (LFS, P  = 0.038) than CTNNB1 low patients. Multivariate analysis confirmed that CTNNB1 expression was an independent prognostic factor for OS among CN-AML. Moreover, CTNNB1 expression level significantly decreased after CR stage ( P  = 0.032) and increased in relapsed stage ( P  = 0.015). Our findings suggest that CTNNB1 is overexpressed and confers a poor prognosis in AML, and could be used as a biomarker in monitoring disease recurrence. [ABSTRACT FROM AUTHOR]

Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a / b levels were significantly increased in AML patients in contrast to controls. Patients with miR-19a/b overexpression were more frequently occurred in female, and had an older age. Moreover, cases with miR-19a overexpression had a higher frequency of U2AF1 , C-KIT and CEBPA mutations, whereas miR-19b overexpressed cases harbored U2AF1 and IDH1/2 mutations. There was no significant association of miR-19a overexpression with complete remission (CR) rate and overall survival (OS) among whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML). However, although miR-19b overexpression was not correlated with CR rate, patients with miR-19b overexpression presented significantly shorter OS in whole-cohort AML and a trend in non-M3 AML and CN-AML patients. Importantly, our data also showed that miR-19a/b expression level at CR phase was lower than diagnosis time, and was returned to primary level even higher when at relapse phase. Our findings revealed that miR-19a/b overexpression were frequent events in de novo AML patients. Moreover, up-regulation of miR-19b expression was associated with poor prognosis and disease recurrence in AML. [ABSTRACT FROM AUTHOR]

Background Invasive fungal disease (IFD) is a major complication of acute leukemia, thus primary antifungal prophylaxis (PAP) is recommended by guidelines. Nevertheless, guidelines might not be commonly followed in developing countries due to economic factors. The primary objectives were to evaluate the implementation rate of PAP in acute leukemia patients in China and to compare the prognosis of IFD with and without PAP. The secondary objectives were to investigate the safety of PAP, clinical characteristics of IFDs and risk factors of breakthrough. Methods This was a retrospective observational single-center study, including non-M3 acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients receiving uniform induction or salvage chemotherapy between 2012 and 2016. Results There were 29.4% of patients without PAP among a total of 248 cases. The incidence of breakthrough proven/probable/possible IFDs was 24.7%, 6.5%, 5.5%, 5.4% and 5.3% in control (no prophylaxis), fluconazole, itraconazole, voriconazole and posaconazole group respectively ( P = 0.007), while the percentage of patients requiring empirical or pre-emptive therapy was 54.8%, 45.7%, 23.3%, 18.9%, 10.5% respectively ( P < 0.001). PAP could also significantly improve IFD-free survival ( P < 0.001) and reduce 90-day overall mortality in patients on AML salvage regimen ( P = 0.021). There were no statistical differences in PAP-related adverse events. Past history of IFD (OR 9.5, P = 0.006) was confirmed to be independent risk factors. Conclusions There are a considerable number of acute leukemia patients without PAP in China, who have higher IFD incidence, increased empiric/pre-emptive antifungal drug use and worse IFD-free survival. [ABSTRACT FROM AUTHOR]

A probabilistic framework is developed for the prognosis of battery packs. It is demonstrated using aging campaign data, that aging models alone may not be sufficient for aging prognosis, and aging model parameter estimation may further improve the accuracy of prognosis. A systematic framework that extends the aging models to battery pack aging and prognosis still remains challenging. We propose a framework that bridges the gap in cell and pack aging prognosis in a probabilistic sense, and further improves the prognosis by estimating the aging model parameters for the pack. The framework is versatile for various applications because it is not restricted to a specific cell chemistry, or a type of aging model. In addition, the proposed framework could distinguish more aged cells as compared to other cells in the pack. Numerical examples are provided to demonstrate the effectiveness of the proposed framework. [ABSTRACT FROM AUTHOR]

A sort of PRCC with distinct eosinophilic cytoplasm named Oncocytic Papillary Renal Cell Carcinoma (OPRCC) has been increasingly attracting the attention of researchers recently. However, owing to the rarity of OPRCC, the clinicopathological and genetic features of the tumor have still not been well elucidated and whether it should be regarded as an independent subtype of PRCC remains controversial. Herein, a cohort of 14 OPRCCs was studied with the aim of revealing the distinct clinicopathological features, facilitating the classification and correct diagnosis of OPRCC. Men and women each accounted for a half of the cohort with the median age of 64 years old. The majority of patients (9/14) were identified by medical examination and the remaining presented with macroscopic haematuria or lumbar pain. Grossly, tumors were well demarcated and varied from 1.5 to 9 cm in diameter. Microscopically, typical OPRCC possessed fine papillary structures with delicate fibrovascular cores, lined with a single layer cell with large, deeply eosinophilic granular cytoplasm and round or polygonal-shaped nucleus exhibiting low nuclear grade in 10 cases (WHO/ISUP grade I-II). Most cases (12/14) possessed hemosiderin-laden and foam-like cells. Focal necrosis presented in 5 cases. Furthermore, solid oncocytoma-like areas appeared in 5 cases and focal sarcomatoid differentiation was identified in 1 case. Immunohistochemically, the majority of tumors presented high expression rates of alpha-methylacylCoA racemase (AMACR), CD10 and vimentin, which were similar to type 2 PRCC. The immune markers including cytokeratin-7 (CK7), KSP-cadherin and EMA exhibited variable positive immunostaining. Genetically, FISH analysis demonstrated trisomy of chromosome 7 in 7 OPRCCs and trisomy of chromosome 17 in 6 OPRCCs. Among 7 male cases, loss of chromosome Y was revealed in 2 cases. Follow-up data was available in 13 patients and only 1 patient died of bone metastasis of the tumor. The other 12 patients were all alive uneventfully at a mean follow-up time of 37 months, indicating that OPRCC is a unique subtype of PRCC with indolent clinical behavior. In conclusion, OPRCCs show a single layer tumor cell of low nuclear grade similar to type 1 PRCC, and abundant eosinophilic cytoplasm resembling type 2 PRCC. Furthermore, the tumor presents the same immunophynotype as type 2 PRCC but the same genetic features and prognosis as type 1 PRCC. OPRCC should be classified as an independent subtype of PRCC with different features from both type 1 and type 2 PRCC. [ABSTRACT FROM AUTHOR]

Background and aims Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have been extensively studied to be associated with many cardiovascular diseases, with the exception of chronic heart failure (CHF). The aim of this study was to determine whether the AGXT2 rs37369 (V140I) polymorphism is associated with risk for and prognosis of CHF in Chinese patients. Methods 1000 CHF patients and 1200 healthy controls were recruited and polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used to determine the genotypes of rs37369 polymorphism. Tube formation assay and transwell migration assay were performed to assess the effects of asymmetric dimethylarginine (ADMA) and to explore the significance of rs37369 polymorphism in the pathogenesis of CHF. 140 CHF patients underwent a median follow-up of 38.7 months by telephone. Results The rs37369 GG genotype was significantly over-represented in CHF patients compared to controls (18.9% vs 14.7%, p = 0.009) and was significantly associated with increased risk of CHF ( p = 0.030), especially in patients with hypertension ( p = 0.021). Besides, the rs37369 GG genotype marginally increased the risk for CHF in smokers. ADMA stimulated migration and inhibited tube formation of cultured human umbilical vein endothelial cells (HUVECs). Overexpression of AGXT2 with pcAGXT2-rs37369-A or G plasmid reversed ADMA-induced HUVECs migration and tube formation. AGXT2 rs37369-A showed increased ADMA degradation activity and marginally prolonged the lifetime of CHF patients. Conclusions ADMA might accelerate the progression of CHF possibly by inhibiting angiogenesis and promoting migration of HUVECs. AGXT2 rs37369 polymorphism is associated with increased risk for CHF, which may due to distinct disparities of alleles in ADMA degradation. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating immune cells (TIICs) play a critical role in breast cancer (BC) prognosis, but little is known regarding the efficacy of endocrine therapy in patients with ER-positive BC with diverse immunological phenotypes. To investigate whether TIICs affect survival after endocrine therapy in patients with different BC molecular subtypes, data were gathered from six studies totaling 1900 samples. CIBERSORTx was used to analyze the invasion of 22 immune cell subpopulations using a bulk gene expression profile. The relationships of immune-related metagenes and immune cell subsets with survival (distant metastasis-free survival, relapse-free survival, and overall survival) were studied using Cox regression models with cell proportions modeled in quartiles. The immune score and IGHG3 and LCK gene activity were linked to a better prognosis. Among the immune cells, monocytes, resting CD4+ memory T cells and plasma cells were correlated with prolonged survival, while neutrophils, Tregs, M0 macrophages, and M2 macrophages were associated with an unfavorable prognosis. Similar effects were reported for the luminal A subtype. In the luminal B subtype, γδ T cells and eosinophils were favorable prognostic factors. Covariate-adjusted multivariate Cox regression analysis revealed that high proportions of resting CD4+ memory T cells and resting dendritic cells were correlated with a good prognosis. Meanwhile, neutrophils were associated with an unfavorable prognosis. Understanding how monocytes and macrophages interact in the tumor microenvironment may be a promising study focus. Comprehensive research on the cellular immune response in tumors could help facilitate the development of new treatments. • Tumor-infiltrating immune cells are associated with survival after endocrine therapy in breast cancer patients. • CIBERSORTx was utilized to infer immune cell subsets using a bulk gene expression profile. • Active IGHG3 and LCK genes are prognostically favorable for endocrine therapy. • Highly infiltrative CD4+ T cells associated with better response to endocrine therapy. [ABSTRACT FROM AUTHOR]

• High PTGES3 expressed in Lung adenocarcinoma. • The over-expression of PTGES3 was related to the poor prognosis of overall survival in LUAD patients (HR = 1.643, 95% CI = 1.140–2.370, p = 0.008). • The expression level of PTGES3 was positively correlated with the infiltrating levels of Th2 cells. Immune-infiltration was positively relationship with overall survival in lung adenocarcinoma (LUAD). Nevertheless, the potential clinical value of PTGES3, especially in terms of prognosis and tumor immune-infiltration in LUAD had not been fully elucidated. Original data available from TCGA and GEO databases and integrated via R3.6.3. Kaplan-Meier and Cox regression methods were used to examine the effect of PTGES3 expression in overall survival, and nomogram was performed to illustrate the correlation between the PTGES3 expression and the risk of LUAD. The associate between PTGES3 and cancer immune characteristics were analyzed via the TISIDB databases. Western blot and RT-qPCR were used to analyze PTGES3 expression in the clinical lung adenocarcinoma tissue samples or non-small cell lung cancer cell lines. PTGES3 mRNA and protein expression were significantly elevated in LUAD compared with normal lung tissues. Up-regulated PTGES3 was significantly associated with pathologic stage and TM stage. Kaplan-Meier survival analysis and subgroup analysis showed that up-regulated PTGES3 was associated with a worse overall survival of LUAD (HR = 1.71 (1.27–2.31), p < 0.001). Multivariate Cox analysis showed that high PTGES3 expression was an independent factor affecting overall survival (HR = 1.64 (1.14–2.37), p < 0.001). GO and KEGG analysis revealed that the cell cycle, regulation of DNA replication, and regulation of innate immune response were enriched. A positive correlation between PTGES3 expression and immune infiltrating levels of Th2 cells was found. PTGES3 may play an important role in the cell cycle and as an independent predictive prognostic biomarker correlates with immune infiltrates in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Our previous research and extensive epidemiological studies reproducibly demonstrated that miR-502 potentially targeted the expression of H4K20 methyltransferase SET8 in a wide spectrum of cancer. Yet, the direct targeting of SET8 by miR-502 has not been definitively proven. The clinical significance of the miR-502/SET8 regulatory circuit is also not clear. Here, we conducted cell-based experiments and clinical studies in a cohort of 279 breast cancer samples. We provide evidence that SET8 is a direct target of miR-502. Treatment with miR-502 or downregulation of SET8 suppressed cell proliferation and cell cycle, and reduced cell migration, invasion and EMT. Clinical analyses showed the miR-502 expression was lower in tumor tissues than in adjacent non-tumor tissues and had a significant inverse correlation with that of SET8. Furthermore, high expression of SET8 was significantly associated with poor overall survival (OS) and disease free survival (DFS) of breast cancer. The low expression ratio of miR-502 to SET8 mRNA was also significantly associated with poor OS. Thus, the miR-502/SET8 regulatory circuit emerges as a key regulator of the pathobiology of cancer and a focal point for possible therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background Recurrent tumour, node and metastasis (rTNM) stage system does not have an outstanding prognostic value for survival outcome of patients with recurrent nasopharyngeal carcinoma (rNPC) and it cannot aid the clinicians to choose the most suitable treatment for these patients. Methods In total, 894 rNPC patients were consecutively enroled. All recurrent (r) tumour (T) stages (rT) and node (N) stages (rN) were stratified as resectable and unresectable based on the imaging data of the head and neck. These stages were re-subdivided into surgical T stages (sT) and surgical N stages (sN) with similar clinical characteristics and death risks and were re-integrated into a new ‘surgical’ stage using a Cox proportional hazards model. Results The 5-year overall survival (OS) was 72.0%, 55.1%, 21.1% and 10.1% in ‘surgical’ stages I, II, III and IV, respectively ( P < 0.001). The ‘surgical’ stage was a significant independent prognostic factor for OS (hazard ratio [HR] 1.78, P < 0.001) and exhibited enhanced prognostic value compared with the rTNM staging system (area under receiver operating characteristics 0.68 versus 0.63, P < 0.001). Endoscopic nasopharyngectomy and intensity-modulated radiation therapy were significant independent positive prognostic factors for the OS of patients with primary lesions in ‘surgical’ stage I/II and ‘surgical’ stage III, respectively ( P < 0.05). A combination of aggressive treatments for loco-regional lesions exhibited a beneficial trend for OS of patients with ‘surgical’ stage IV ( P > 0.05). Conclusions Compared with the rTNM stage system, the ‘surgical’ staging system exhibited enhanced prognostic value for rNPC patient survival and could aid clinicians in choosing the most suitable treatment for rNPC patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinicopathological and molecular characteristics of ELOC(TCEB1)-mutant renal cell carcinoma. Sanger sequencing was used to assess 32 cases originally diagnosed as clear cell renal cell carcinoma with CK7 positive and/or fibromyomatous stroma. Of these, 4 patients with ELOC(TCEB1) gene mutation were screened, and their clinicopathological data were collected for histomorphological observation, immunohistochemical staining, and follow-up, and relevant pieces of literature were reviewed. The 4 patients with ELOC(TCEB1) mutations were all males and aged between 57 and 64 years (median age: 59 years old). The tumor was located in the renal cortex, with a diameter of 2–3.5 cm. The cross-section was grayish-yellow and grayish brown, solid and nodular, and clearly demarcated from the surrounding tissues. Of the 4 patients, 3 harbored a thick fibrous pseudocapsule rich in smooth muscle and were separated from the surrounding normal renal tissue, and 2 of them showed focal invasion into the pseudocapsule, whereas 1 patient had no capsule but had focal invasion into the surrounding renal parenchyma. The tumor tissues mainly exhibited elongated or branched aciniform or tubular structures, commonly accompanied by interspersed small cystic and focal clustered short papillary structures. The cytoplasm of the tumor cells was rich and lightly stained, and the nuclear grading ranged from 1 to 2. All patients showed loose edema in the stroma, and 2 patients showed a small number of interspersed smooth muscle bundles. All 4 patients showed EMA, CA9, AMACR, and TCEB1 expression, and TCEB1 was mainly located in the nucleus. Vimentin, CK7, and CD10 expressions were observed in most cases; CD117, TFE3, HMB45, and melanA were not expressed in all tumors; the expression rate of Ki67 was 3%− 8%. All 4 patients had a point mutation in ELOC(TCEB1) Y79C. The patients were followed up for 24–93 months (mean 49 months), and all of them survived to date without recurrence or metastasis. ELOC(TCEB1)-mutant renal cell carcinoma is a rare type of renal cell carcinoma, which tends to occur in middle-aged and elderly men. The main characteristics of this tumor are the branching alveolar or tubular structure with clustered short papillae, presence of fibromyomatous stroma, and the expression of CK7, CA9, CD10, and AMACR. Positive TCEB1 nuclear staining may be an important marker and the Sanger sequencing method is helpful for the diagnosis of this type of RCC. Most patients harbor tumors exhibiting low nuclear grade and inert clinical behavior, and a few tumors exhibit high nuclear grade and aggressive characteristics. [ABSTRACT FROM AUTHOR]

Background Abnormal functional brain activity has been revealed in patients with Posttraumatic Stress Disorder (PTSD) in recent years, while the recovery neuromechanism of PTSD has not yet been elucidated. The aim of this study was to investigate the altered spontaneous brain activity in treatment-naïve chronic PTSD patients before and after 12 weeks׳ treatment with paroxetine. Methods Twenty-one earthquake-related PTSD patients and seventeen traumatized controls underwent a resting functional magnetic resonance imaging (Rs-fMRI) scan at baseline. Amplitude of low-frequency fluctuation (ALFF) was calculated and compared between PTSD patients and controls. Then, the PTSD group completed 12 weeks of treatment with paroxetine, and Rs-fMRI was repeated to compare with the baseline. Lastly, correlation analyses of ALFF values within altered brain areas were conducted. Results Hyperactive function of visual cortex was observed in PTSD patients before and after treatment. After treatment, significantly increased ALFF values were observed in the left orbitofrontal cortex (OFC), while decreased ALFF values were found in the precuneus. Interestingly, a negative correlation between the mean ALFF values of OFC and those of precuneus and visual cortex was only observed in controls, but not in PTSD patients pre- or post-treatment. Limitations A corresponding control condition was absent in this study. Conclusion The findings showed that manipulating regional spontaneous activity of precuneus and OFC could be a potential prognostic indicator of PTSD. However, hyperactive function of visual cortex and disrupted connections between OFC, precuneus and visual cortex did not reverse after treatment, which could be a potential target for further treatment. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3′-UTR correlated positively with TBC1D1 6 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D1 6 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC 50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D1 6 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors of the ureter are extremely rare. There are only a few case reports in the past decades. Their clinicopathologic features, therapy and prognosis are not that clear. 5 cases of ureteral neuroendocrine tumors were collected and reviewed of the literature. Histomorphology, immunophenotype and ultrastructural features were observed by HE, immunohistochemistry, special staining and electron microscopy. The clinical pathological data were retrospectively analyzed and followed up. Among the 5 patients, 1 was female and 4 were male, aged 62–82 years. 2 cases manifested intermittent hematuria, 1 had lower abdominal pain with frequent urination and dysuria, 1 with hydronephrosis, and 1 had no manifestations. All the 5 patients were treated with nephroureterectomy, 3 of which were also treated with excision of bladder cuff, 1 also had lymphadenectomy. On presentation, 2 cases in T2N0M0 (stage II), 2 cases in T3N0M0 (stage III), and 1case in T3N2M0 (stage IV). 2 cases were small cell neuroendocrine carcinoma, 1 was large cell neuroendocrine carcinoma and 2 were atypical carcinoid. The tumor cells were positive for neuroendocrine markers (CD56, CgA, Syn). 1 case of vimentin-positive small cell neuroendocrine carcinoma has a very good prognosis. Grimelius stain and electron microscopy observation showed numerous neuroendocrine granules in the cytoplasm. Ureteral neuroendocrine tumors are extremely rare. Neuroendocrine markers (CD56, CgA, Syn) and epithelial markers (CKpan, CK7) are usually helpful. Grimelius special staining and electron microscopy observation can help to make a final diagnosis. Radical surgery together with postoperative adjuvant chemotherapy can improve the survival of patients. Vimentin may play a role in predicting the prognosis. [ABSTRACT FROM AUTHOR]