[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. PREVENTION RELEVANCE: We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

Increased RNA editing sites revealed as potential novel biomarkers for diagnosis in primary Sjögren's syndrome.

BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy. CONCLUSION: These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.

Focusing on testosterone levels in male: A half-longitudinal study of polycyclic aromatic hydrocarbon exposure and diastolic blood pressure in coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) can interfere with testosterone levels, and low levels of testosterone are associated with increased cardiovascular events. To explore the role of testosterone in PAHs exposure and cardiovascular health, we used data from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) and a longitudinal database of 332 male coke oven workers from China. The urine PAHs, tobacco metabolites and plasma testosterone levels of coke oven workers were measured. There were inverse associations between serum (plasma) testosterone concentrations and the risk of dysarteriotony and dyslipidemia among the NHANES participants and coke oven workers. The results of the cross-lagged panel analysis among workers showed that the decrease in testosterone preceded the increase in diastolic blood pressure (DBP), and the absolute value of the path coefficient from baseline testosterone to follow-up DBP (ß2 = -8.162, P = 0.077) was significantly larger than the absolute value of the path coefficient from baseline DBP to follow-up testosterone (ß1 = -0.001, P = 0.781). Results from the half-longitudinal mediation analysis showed that baseline hydroxyfluorene predicted significant decreases in plasma testosterone from baseline to follow-up (path a: 0.71, 95% CI: 1.26, -0.16), whereas plasma testosterone at baseline also predicted significant increments in DBP from baseline to follow-up (path b: 9.22, 95% CI: 17.24, -1.19). The indirect effect of PAHs on DBP via plasma testosterone level was marginally significant (test for indirect effects a*b (P = 0.08)). In conclusion, testosterone level is a longitudinal precursor to increased DBP and plays an essential role in the association between PAHs exposure and damage to the cardiovascular system. Coke oven workers with low plasma testosterone levels are more likely to experience adverse changes in blood pressure and lipid levels after exposure to PAHs.

Experimental investigation of the creep damage evolution of coal rock around gas extraction boreholes at different water contents.

The creep process of the coal rock around the extraction boreholes under stress-water coupling is an important factor affecting the stability of the boreholes. To study the influence of the water content of perimeter of the coal rock around the boreholes on its creep damage, a creep intrinsic model considering water damage was established by introducing the plastic element model from the Nishihara model. To study the steady-state strain and damage evolution of coal rocks containing pores, and verify the practicality of the model, a graded loading water-bearing creep test was designed to explore the role of different water-bearing conditions in the creep process. The following conclusions were obtained: 1) water has a physical erosion and softening water wedge effect on the perimeter of the coal rock around the boreholes, which affects the loading axial strain and displacement of the perforated specimens; 2) an increase in water content reduces the time taken for perforated specimens to enter the creep phase, making the accelerated creep phase come earlier; 3) the parameters of the water damage model are considered to be exponentially related with the water content. The experimental data are similar to the results of the model parameters, and the model shows some practicality; 4) the damage variables in the accelerated creep phase increase rapidly throughout the creep process, leading to local instability in the borehole. The findings of the study provide important theoretical implications for the study of instability in gas extraction boreholes.

CASMART, a one-step CRISPR Cas12a-mediated isothermal amplification for rapid and high-resolution digital detection of rare mutant alleles.

Convenient, ultrasensitive, and accurate detection of rare variants is essential for early cancer diagnosis and precision medicine, however, despite years of efforts, tools that have all these qualities remain elusive. Here, we developed a one-step CRISPR/Cas12a-based digital diagnostic platform for accurately quantifying mutant alleles, referred to as the CRISPR ASsoaciated Mutation Allele Rapid Test (CASMART). The platform accurately quantifies the variant allele frequency of EGFR L858R within 1 h at 42 °C and can detect mutant targets as low as 0.3 copies/µL (0.498 aM) in mock multiplex cfDNA samples. We further investigated the applicability of CASMART using human genomic samples with confirmed EGFR L858R mutations previously measured variant allele frequency by next-generation sequencing. Comparison across platforms revealed equivalent detection performance (Pearson's correlation coefficient, R2 = 0.9208) and high quantification accuracy for mutation allele frequency (intraclass correlation coefficient = 0.959). Our one-step approach enables easy and accurate variant allele frequency measurement of rare mutant alleles without PCR instrumentation, while the assay time was reduced by approximately half compared to the digital PCR with the shortest turnaround. The CASMART is an alternative to conventional single nucleotide polymorphism detection methods with great potential as a next-generation biosensor for rapidly quantifying the variant allele fraction, especially in resource-limited settings.

Current development and prospects of deep learning in spine image analysis: a literature review.

Background and Objective: As the spine is pivotal in the support and protection of human bodies, much attention is given to the understanding of spinal diseases. Quick, accurate, and automatic analysis of a spine image greatly enhances the efficiency with which spine conditions can be diagnosed. Deep learning (DL) is a representative artificial intelligence technology that has made encouraging progress in the last 6 years. However, it is still difficult for clinicians and technicians to fully understand this rapidly evolving field due to the diversity of applications, network structures, and evaluation criteria. This study aimed to provide clinicians and technicians with a comprehensive understanding of the development and prospects of DL spine image analysis by reviewing published literature. Methods: A systematic literature search was conducted in the PubMed and Web of Science databases using the keywords "deep learning" and "spine". Date ranges used to conduct the search were from 1 January, 2015 to 20 March, 2021. A total of 79 English articles were reviewed. Key Content and Findings: The DL technology has been applied extensively to the segmentation, detection, diagnosis, and quantitative evaluation of spine images. It uses static or dynamic image information, as well as local or non-local information. The high accuracy of analysis is comparable to that achieved manually by doctors. However, further exploration is needed in terms of data sharing, functional information, and network interpretability. Conclusions: The DL technique is a powerful method for spine image analysis. We believe that, with the joint efforts of researchers and clinicians, intelligent, interpretable, and reliable DL spine analysis methods will be widely applied in clinical practice in the future.

Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF-κB Signaling Pathway.

Objective: To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods: Rats were randomly divided into 4 groups: control group (n = 6) were injected with the same amount of normal saline; ALF group (n = 10) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 µg/kg); ALF+JDHY group (n = 10) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group (n = 10) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1ß, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results: JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly (P < 0.01), increase PTA and PLT (P < 0.01), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased (P < 0.01). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1ß, and TNF-α while increasing the level of IL-10 and IL-13 (P < 0.01). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased (P < 0.01). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKßα, and IKKß in the ALF rat tissues. Conclusions: JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

The Relationship between MALAT1 Polymorphism rs3200401 C > T and the Risk of Overall Cancer: A Meta-Analysis.

Background and Objectives: At present, the association between the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) polymorphism rs3200401 C > T and cancer risk remain controversial. The aim of this meta-analysis was to assess the association between rs3200401 C > T and cancer susceptibility. Materials and Methods: The databases of PubMed, EMBASE and Web of Science were searched for literature published in English until 1 September 2021. The odd ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association in five genetic models. Heterogeneity was assessed using the Q-test and I2 test. Begg's funnel plot and Egger's linear regression test were conducted to assess publication bias. Meta-regression analysis was used to explore potential sources of heterogeneity. Trial sequential analysis (TSA) was performed to validate the reliability of the results. Results: A total of 10 case-control studies involving 6630 cases and 7457 controls were included in this study. The pooled ORs showed no significant association between MALAT1 rs3200401 C > T and cancer risk in five genetic models. Similarly, the association was not found in the subgroups of control source, ethnicity and study quality. In the cancer type subgroup, the results demonstrated that the T allele increased the risk of colorectal cancer (CRC) compared with the C allele. (C vs. T: OR, 1.16; 95% CI, 1.01-1.33). Conclusion: In the current meta-analysis, we found no significant association between MALAT1 polymorphism rs3200401 C > T and overall cancer risk. However, the rs3200401 C > T may be linked to a higher risk of CRC, which needs more studies to be further confirmed.

A retrospective study on unresectable or inoperable head and neck cancers treated with stereotactic ablative brachytherapy.

Purpose: The aim of the present study was to assess the clinical efficacy and safety of stereotactic ablative brachytherapy (SABT) for unresectable or inoperable head and neck cancers. Material and methods: This study retrospectively assessed clinical data of 37 patients with unresectable or inoperable head and neck cancers treated with SABT from October 2016 to October 2021. Variables evaluated included local efficacy, local control rate (LCR), overall survival (OS) rate, and radiological adverse effects. Results: The median follow-up was of 34 months (range, 5-59 months), and LCR at 6, 12, and 24 months was 89.2%, 78.2%, and 69.4%, respectively. The median survival time was 16 months [95% confidence interval (CI): 10.5-21.5 months], and the OS rate at 6, 12, and 24 months was 97.3%, 70.3%, and 34.5%, respectively. The results of univariate analysis revealed that the type of pathology and gross tumor volume (GTV) D90 were related to LCR (p < 0.05). However, the type of pathology, GTV D90, age, and implantation site were related to OS rate (p < 0.05). The results of multivariate analysis showed that the type of pathology and GTV D90 were substantially related to LCR and OS rate (p < 0.05). The evaluation of post-operative radiological adverse reactions revealed that seven cases (18.9%) developed grade 1-2 skin reactions, four cases (10.8%) developed grade 1-2 oral mucosal outcomes, and no cases developed grade 3 or higher adverse reactions. Post-operative seed dislocation occurred in three patients with tongue cancer. Conclusions: SABT has produced good local control and mild adverse reactions in the treatment of unresectable or inoperable head and neck cancers. Additionally, it is safe, feasible, minimally invasive, and has fewer adverse effects than other treatment modalities.

A novel immunodiagnosis panel for hepatocellular carcinoma based on bioinformatics and the autoantibody-antigen system.

Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen-antibody system) were taken as candidate tumor-associated antigens (TAAs). Enzyme-linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model. Eleven TAAs were selected (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2). The titer of six autoantibodies (PCNA, AAGAB, CDC37L1, TAF7L, DUSP6, and ZIC2) had a significant difference in any of the pairwise comparisons among the HCC, liver cirrhosis, and normal control groups. The titer of these autoantibodies had an increasing tendency. Finally, an optimum diagnostic model was constructed with the six autoantibodies. The AUCs were 0.826 in the train set and 0.773 in the test set. The area under the curve (AUC) of this panel for diagnosing early HCC was 0.889. The diagnostic ability of the panel reduced with the progress of HCC. The positive rate of the panel in diagnosing alpha-fetoprotein (AFP)-negative patients was 75.6%. For early HCC, the sensitivity of the combination of AFP with the panel was 90.9% and superior to 53.2% of AFP alone. The novel immunodiagnosis panel combining AFP may be a new approach for the diagnosis of HCC, especially for early-HCC cases.

Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis.

Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.

The clinical efficacy of computed tomography-guided 125I particle implantation combined with arterial infusion chemotherapy in the treatment of pancreatic cancer.

AIMS: This study aimed to investigate the clinical value of 125I radioactive particle implantation combined with regional arterial chemotherapy perfusion in the treatment of pancreatic cancer. SUBJECTS AND METHODS: The clinical data of 23 patients with pancreatic cancer were retrospectively analyzed, and the patients were divided into two groups. In the observation group, 11 patients were injected with radioactive particles in combination with regional arterial chemotherapy. In the control group, 12 patients were treated with simple regional arterial perfusion chemotherapy. Curative effect, pain relief, survival period, and adverse reactions were compared between the two groups. RESULTS: The proportion of patients was significantly higher in the observation group (complete remission + partial remission) (72.73%) than in the control group (41.67%). The 6-month and 9-month survival rates in the experimental group were 91.7% and 50%, respectively, while those in the control group were 63.6% and 18.2%, respectively, with significantly statistical difference. The 12-month survival rate in the experimental group was 16.7% and was significantly higher than that in the control group (8.3%). The experimental group should greater improvement in pain symptoms than the control group, and there was no statistical difference between the two groups except in complications of 125I radioactive particle implantation. CONCLUSIONS: We conclude that 125I radioactive particle implantation combined with regional arterial perfusion chemotherapy is an effective and comprehensive treatment for advanced pancreatic cancer.

Development and validation of a score to predict mortality in ICU patients with sepsis: a multicenter retrospective study.

BACKGROUND: Early and accurate identification of septic patients at high risk for ICU mortality can help clinicians make optimal clinical decisions and improve the patients' outcomes. This study aimed to develop and validate (internally and externally) a mortality prediction score for sepsis following admission in the ICU. METHODS: We extracted data retrospectively regarding adult septic patients from one teaching hospital in Wenzhou, China and a large multi-center critical care database from the USA. Demographic data, vital signs, laboratory values, comorbidities, and clinical outcomes were collected. The primary outcome was ICU mortality. Through multivariable logistic regression, a mortality prediction score for sepsis was developed and validated. RESULTS: Four thousand two hundred and thirty six patients in the development cohort and 8359 patients in three validation cohorts. The Prediction of Sepsis Mortality in ICU (POSMI) score included age ≥ 50 years, temperature < 37 °C, Respiratory rate > 35 breaths/min, MAP ≤ 50 mmHg, SpO2 < 90%, albumin ≤ 2 g/dL, bilirubin ≥ 0.8 mg/dL, lactate ≥ 4.2 mmol/L, BUN ≥ 21 mg/dL, mechanical ventilation, hepatic failure and metastatic cancer. In addition, the area under the receiver operating characteristic curve (AUC) for the development cohort was 0.831 (95% CI, 0.813-0.850) while the AUCs ranged from 0.798 to 0.829 in the three validation cohorts. Moreover, the POSMI score had a higher AUC than both the SOFA and APACHE IV scores. Notably, the Hosmer-Lemeshow (H-L) goodness-of-fit test results and calibration curves suggested good calibration in the development and validation cohorts. Additionally, the POSMI score still exhibited excellent discrimination and calibration following sensitivity analysis. With regard to clinical usefulness, the decision curve analysis (DCA) of POSMI showed a higher net benefit than SOFA and APACHE IV in the development cohort. CONCLUSION: POSMI was validated to be an effective tool for predicting mortality in ICU patients with sepsis.

TSPAN1, TMPRSS4, SDR16C5, and CTSE as Novel Panel for Pancreatic Cancer: A Bioinformatics Analysis and Experiments Validation.

Pancreatic cancer is a lethal malignancy with a poor prognosis. This study aims to identify pancreatic cancer-related genes and develop a robust diagnostic model to detect this disease. Weighted gene co-expression network analysis (WGCNA) was used to determine potential hub genes for pancreatic cancer. Their mRNA and protein expression levels were validated through reverse transcription PCR (RT-PCR) and immunohistochemical (IHC). Diagnostic models were developed by eight machine learning algorithms and ten-fold cross-validation. Four hub genes (TSPAN1, TMPRSS4, SDR16C5, and CTSE) were identified based on bioinformatics. RT-PCR showed that the four hub genes were expressed at medium to high levels, IHC revealed that their protein expression levels were higher in pancreatic cancer tissues. For the panel of these four genes, eight models performed with 0.87-0.92 area under the curve value (AUC), 0.91-0.94 sensitivity, and 0.84-0.86 specificity in the validation cohort. In the external validation set, these models also showed good performance (0.86-0.98 AUC, 0.84-1.00 sensitivity, and 0.86-1.00 specificity). In conclusion, this study has identified four hub genes that might be closely related to pancreatic cancer: TSPAN1, TMPRSS4, SDR16C5, and CTSE. Four-gene panels might provide a theoretical basis for the diagnosis of pancreatic cancer.

The Perfusion Features of Recurrent Hepatocellular Carcinoma After Radiofrequency Ablation Using Contrast-Enhanced Ultrasound and Pathological Stemness Evaluation: Compared to Initial Tumors.

Objective: To investigate the perfusion features of local recurrence in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) with contrast-enhanced ultrasound (CEUS) and pathological correlation, as well as to compare with those of initial HCC. Methods: From 2010 to 2018, 42 patients with recurrent HCC after RFA were enrolled in this study. The initial HCC patients included 32 males and 10 females with an average age of 58.2 ± 8.1 years. The CEUS images for initial HCC lesions and local recurrence after RFA were compared. The perfusion features were analyzed, including enhancement time, process, boundary, morphology, washout time, washout degree, feeding vessels, and internal necrosis. H&E staining and CD133/EpCAM staining were performed with biopsy samples for the stemness study. Results: According to CEUS, 59.5% of initial HCC lesions had centripetal enhancement, and 61.9% of recurrent HCC lesions had homogeneous enhancement in the arterial phase (p < 0.001). A total of 73.8% of initial HCC lesions had well-defined margins at the peak, and 81.0% of recurrent HCC lesions had poorly defined margins (p < 0.001). A total of 78.6% of initial HCC lesions had regular morphology at the peak, and 83.3% of recurrent HCC lesions were irregular (p < 0.001). Feeding vessels were more frequently found in initial HCC lesion (71.4%) than in recurrent HCCs (38.1%, p = 0.002). In the late phase, 60% of initial HCCs had marked washout while 83.3% of recurrent HCC lesion had marked washout (p = 0.019). A total of 31.3% of the initial HCC lesions had internal necrosis areas while only 7.1% of recurrent HCC lesions had internal necrosis areas (p = 0.035). In tumors 3-5 cm in size, the washout time of recurrent HCCs was shorter than that of initial HCCs (50.3 ± 13.5 s vs. 75.6 ± 45.8 s, p = 0.013). Pathological staining showed that the tumor stem cell markers (CD133 and EpCAM) were both highly expressed in recurrent samples compared with initial tumor samples (CD133+: 19 vs. 5%, p = 0.002; EpCAM+:15 vs. 6%, p = 0.005). Conclusions: Recurrent HCC after RFA had more homogeneous enhancement with a poorly defined border, marked washout, and fewer less feeding vessels and inner necrosis areas compared to initial HCC. The stemness study also found upregulated stemness in recurrent HCC. These specific features might be related to the aggressive biological behavior of recurrent HCC.

Improving B-mode ultrasound diagnostic performance for focal liver lesions using deep learning: A multicentre study.

BACKGROUND: The diagnosis performance of B-mode ultrasound (US) for focal liver lesions (FLLs) is relatively limited. We aimed to develop a deep convolutional neural network of US (DCNN-US) for aiding radiologists in classification of malignant from benign FLLs. MATERIALS AND METHODS: This study was conducted in 13 hospitals and finally 2143 patients with 24,343 US images were enrolled. Patients who had non-cystic FLLs with pathological results were enrolled. The FLLs from 11 hospitals were randomly divided into training and internal validations (IV) cohorts with a 4:1 ratio for developing and evaluating DCNN-US. Diagnostic performance of the model was verified using external validation (EV) cohort from another two hospitals. The diagnosis value of DCNN-US was compared with that of contrast enhanced computed tomography (CT)/magnetic resonance image (MRI) and 236 radiologists, respectively. FINDINGS: The AUC of ModelLBC for FLLs was 0.924 (95% CI: 0.889-0.959) in the EV cohort. The diagnostic sensitivity and specificity of ModelLBC were superior to 15-year skilled radiologists (86.5% vs 76.1%, p = 0.0084 and 85.5% vs 76.9%, p = 0.0051, respectively). Accuracy of ModelLBC was comparable to that of contrast enhanced CT (both 84.7%) but inferior to contrast enhanced MRI (87.9%) for lesions detected by US. INTERPRETATION: DCNN-US with high sensitivity and specificity in diagnosing FLLs shows its potential to assist less-experienced radiologists in improving their performance and lowering their dependence on sectional imaging in liver cancer diagnosis.

YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis.

Ovarian cancer endangers the life of women worldwide. Plenty of lncRNAs have been found modulating the progression of ovarian cancer. Meanwhile, lncRNA DSCR8 (Down syndrome critical region 8) has been reported as an oncogene in hepatocellular carcinoma. In this study, we aimed to search the function of DSCR8 in ovarian cancer. qRT-PCR analysis assessed the expression of DSCR8 in ovarian cancer cells. EdU assay and colony formation assay was used to test cell proliferation. Flow cytometry analysis and TUNEL assay were conducted to investigate cell apoptosis. Wound healing assay and transwell invasion assay assessed cell migration and invasion. DSCR8 was significantly up-regulated in ovarian cancer cells. Inhibited DSCR8 could suppress the progression of ovarian cancer. Also, YY1 could activate the expression of DSCR8 in ovarian cancer cells. Meanwhile, DSCR8/miR-3192-5p/YY1 axis was identified in ovarian cancer cells. MiR-3192-5p could function as tumor suppresser in ovarian cancer cells. Furthermore, DSCR8 and YY1 (Yin Yang 1) transcription factor could play the regulatory network in ovarian cancer cells. In a word, YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis.