The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

Biomarker cystatin B expression correlates with pathogenesis in cervical cancer.

OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic malignancies worldwide. Although rapid improvements have been made regarding its prevention and treatment, little is known about disease pathogenesis and the clinical relevance of reliable biomarkers. The present study evaluated the expression of cystatin B (CSTB) as a potential biomarker of CC. METHODS: Tissue microarray analysis and immunohistochemical staining were performed to detect CSTB expression, while CSTB mRNA and protein expression levels of freshly isolated CC tissue were measured by quantitative real-time PCR and western blot, respectively. Bioinformatics were used to analyze the CSTB co-expression network and functional enrichments. RESULTS: We observed high CSTB mRNA and protein expression levels in CC tissues, which was confirmed by tissue microarray in a comparison with paired adjacent non-cancerous cervical tissue samples. CSTB gene enrichments and associations with co-expressed genes were also observed. Further analysis showed that elevated CSTB expression was associated with pathological progress in CC. CONCLUSION: Our data demonstrate that CSTB has the potential to be used as a tissue biomarker with clinical value in patients with CC, which may aid the development of intervention strategies.

Matrine improves the hepatic microenvironment and reverses epithelial-mesenchymal transition in hepatocellular carcinoma by inhibiting the Wnt-1/ß-catenin signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.

Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.

BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

GaN JBS Diode Device Performance Prediction Method Based on Neural Network.

GaN JBS diodes exhibit excellent performance in power electronics. However, device performance is affected by multiple parameters of the P+ region, and the traditional TCAD simulation method is complex and time-consuming. In this study, we used a neural network machine learning method to predict the performance of a GaN JBS diode. First, 3018 groups of sample data composed of device structure and performance parameters were obtained using TCAD tools. The data were then input into the established neural network for training, which could quickly predict the device performance. The final prediction results show that the mean relative errors of the on-state resistance and reverse breakdown voltage are 0.048 and 0.028, respectively. The predicted value has an excellent fitting effect. This method can quickly design GaN JBS diodes with target performance and accelerate research on GaN JBS diode performance prediction.

Single event effects prediction of MOSFET device using deep learning.

Single event effect (SEE) is an important problem in the reliability research of integrated circuits. The study of SEE of traditional MOSFET devices is mainly based on simulation software, which is characterized by slow simulation speed, large computation and time-consuming. In this paper, a SEE research method based on deep learning is proposed. The method relies on 28 nm MOSFET. The complete drain transient current pulse, transient current peak value and total collected charge can be obtained in a short time by inputting relevant parameters that affect the SEE. The accuracy of the network for predicting transient current peak and total collected charge is 96.95% and 97.53% respectively, and the mean goodness of fit of the network for predicting the drain transient current pulse curve is 0.985. Compared with TCAD Sentaurus software, the simulation speed is increased by 5.89 × 103and 1.50 × 103times respectively. This method has good prediction effect and provides a new possibility for the study of SEE.

Implementation of early rehabilitation for critically ill children in China: A survey and narrative review of the literature.

Introduction: The focus of this survey was to understand the current status of implementation of early rehabilitation for critically ill children in China. We also reviewed the available literature on this topic for further insights to inform its future development. Materials and methods: We used a cross-sectional study design to survey tertiary hospitals nationwide. Questionnaires were distributed via the social media platform "WeChat Questionnaire Star" within the framework of the Rehabilitation Group of the Pediatrics Branch of the Chinese Medical Association. A narrative literature review on the implementation of the early rehabilitation for critically ill pediatric and/or adult patients was carried out. Results: A total of 202 valid questionnaires were received. About half (n = 105, 52.0%) of respondent hospitals reported that they implement early rehabilitation for critically ill children. Among these 105 hospitals, 28 implemented a continuous chain of early rehabilitation. A total of 24 hospitals had set up permanent specialized centralized early rehabilitation units for critically ill children. Implications and future directions: Early rehabilitation for critically ill children is not widely available in China and only a minority of hospitals implement a continuous chain of early rehabilitation. To improve this undesirable situation, we suggest creating a two-level integrated system comprising centralized early rehabilitation units and surrounding early rehabilitation networks within a region.

The accelerated design of the nanoantenna arrays by deep learning.

Nanoantenna fusion photonics and nanotechnology can manipulate light through the ultra-thin structure composed of sub-wavelength antennas, and meet the important requirements for miniaturized optical components, completely changing the field of optics. However, the device design process is still time-consuming and consumes computing resources. Besides, the professional knowledge requirements of engineers are also high. Relying on the algorithm's inference ability and excellent computing ability, artificial intelligence has great potential in the fields of material design, material screening, and device performance prediction. However, the deep learning (DL) requires a mass of data. Therefore, this article proposes a method for the forward and inverse design of nanoantenna based on DL. Compared with the previous work, the network uses a two-dimensional matrix as input, which has a simple structure and is more suitable for the advantages of deep netural network. Simultaneously, the small datasets can be used to achieve higher accuracy. In the forward prediction, 100% of the data error is less than 0.007; in the inverse prediction, the data with error less than 0.05 accounted for 90%, 99.8% and 100% of the length, height, and width's datasets. It demonstrates that the method can improve the automation of the design process and reduce the consumption of computer resources.

Prediction of electrical properties of FDSOI devices based on deep learning.

Fully depleted Silicon on insulator technology (FDSOI) is proposed to solve the various non-ideal effects when the process size of integrated circuits is reduced to 45 nm. The research of traditional FDSOI devices is mostly based on simulation software, which requires a lot of calculation and takes a long time. In this paper, a deep learning (DL) based electrical characteristic prediction method for FDSOI devices is proposed. DL algorithm is used to train the simulation data and establish the relationship between the physical parameters and electrical characteristics of the device. The network structure used in the experiment has high prediction accuracy. The mean square error of electrical parameters and transfer characteristic curve is only 4.34 × 10-4and 2.44 × 10-3respectively. This method can quickly and accurately predict the electrical characteristics of FDSOI devices without microelectronic expertise. In addition, this method can be extended to study the effects of various physical variables on device performance, which provides a new research method for the field of microelectronics.

Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index.

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.

Sarcopenia and Systemic Inflammation Response Index Predict Response to Systemic Therapy for Hepatocellular Carcinoma and Are Associated With Immune Cells.

Background: Systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states. Methods: We reviewed 160 patients with HCC treated with TKIs and ICIs. The patients' psoas muscle size was measured on axial computed tomography scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients' clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated. Results: Sarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group. Conclusion: Sarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

Removal of Metal Ions in Phosphoric Acid by Electro-Electrodialysis with Cross-Linked Anion-Exchange Membranes.

There are numerous metallic impurities in wet phosphoric acid, which causes striking negative effects on industrial phosphoric acid production. In this study, the purification behavior of metallic impurities (Fe, Mg, Ca) from a wet phosphoric acid solution employing the electro-electrodialysis (EED) technology was investigated. The cross-linked polysulfone anion-exchange membranes (AEMs) for EED were prepared using N,N,N',N'-tetramethyl-1,6-hexanediamine (TMHDA) to achieve simultaneous cross-linking and quaternization without any cross-linkers or catalysts. The performance of the resulting membranes can be determined using quaternization reagents. When the molar ratio of trimethylamine/TMHDA/chloromethylated polysulfone is 3:1:1, the cross-linked membrane CQAPSU-3-1 exhibits lower water swelling and membrane area resistance than the non-cross-linked membrane. The low membrane area resistance of CQAPSU-3-1 with long alkyl chains is obtained due to the hydrophilic-hydrophobic microphase separation structure formed by TMHDA. EED experiments with different initial phosphoric acid concentrations of 0.52 and 1.07 M were conducted to evaluate the phosphoric acid purification of different AEMs. The results show that the EED experiments were more suitable for the purification of wet phosphoric acid solution at low concentrations. It was found that the phosphoric acid concentration in the anode compartment could be increased from 0.52 to 1.04 M. Through optimization, with an initial acid concentration of 0.52 M, CQAPSU-3-1 exhibits an enhanced metallic impurity removal ratio of higher than 72.0%, the current efficiency of more than 90%, and energy consumption of 0.48 kWh/kg. Therefore, CQAPSU-3-1 exhibits much higher purification efficiency than other membranes at a low initial phosphoric acid concentration, suggesting its potential in phosphoric acid purification application.

Cross-sectional study of mental health related knowledge and attitudes among care assistant workers in Guangzhou, China.

BACKGROUND: Care assistant workers (CAWs) are a part of a new pattern of mental health care providers in China and play a significant role in bridging the human resource shortage. CAWs in China mainly include community cadres, community mental health staff, and community policemen. The mental health related knowledge and attitudes of CAWs could influence their mental health care delivery. This study aimed to assess mental health related knowledge and attitudes of CAWs in Guangzhou, China. METHODS: In November 2017, a study was conducted among 381 CAWs from four districts of Guangzhou, China. Participants were assessed using the Perceived Devaluation and Discrimination Scale (PDD), the Mental Health Knowledge Schedule (MAKS), and the Mental illness: Clinicians' Attitudes (MICA) Scale. Data were analyzed by descriptive statistics, ANOVA, Bonferroni corrections and multivariable linear regression. RESULTS: The mean scores (standard deviation) of PDD, MAKS and MICA were 36.45 (6.54), 22.72 (2.56), and 51.67 (7.88), respectively. Univariate analyses showed that the older CAWs, community policemen and those who were less willing to deliver care to people with mental illness had significant higher MICA scores when compared with other staff (P < 0.001). Multivariable linear regression showed that after controlling for key variables, care willingness and PDD total score were positively associated with the MICA total score (all P < 0.05), while attitudes on additional items were significant negatively with the MICA total score (all P < 0.01). CONCLUSION: These findings suggest negative attitudes towards people with mental disorders among CAWs are common, especially among older staff. Community policemen suggest that they applied stereotypes of "violent mentally ill" people to all people they deal with who have mental disorders. The results also indicate human rights are being paid some attention to now, but need to be further continually improved in the future. Strategies for improving such negative attitudes and reducing the perceived stigma and discrimination should be carried out towards particular staff groups in an anti-stigma programme in Guangzhou, China.

18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Metabolic Parameters Before and After Neoadjuvant Chemotherapy Can Predict the Postoperative Prognosis of Locally Advanced Gastric Cancer.

Objective: To explore the value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) metabolic parameters before and after neoadjuvant chemotherapy in predicting histopathological response and prognosis of locally advanced gastric cancer. Materials and Methods: A total of 56 patients with locally advanced gastric cancer underwent 18F-FDG PET/CT before and after neoadjuvant chemotherapy. The maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the lesions were measured before and after neoadjuvant chemotherapy. The percentage changes in the maximum standardized uptake value (ΔSUVmax%), mean standardized uptake value (ΔSUVmean%), metabolic tumor volume (ΔMTV%), and total lesion glycolysis (ΔTLG%), which were derived from 18F-FDG PET/CT, were calculated, and the cutoff values were determined by receiver operating characteristic curve analysis. Differences in progression-free survival (PFS) and overall survival (OS) between groups dichotomized by these cutoffs were analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. Results: The patients were divided into histopathological responders and nonresponders according to the following cutoff values: 58.8% SUVmax reduction, 45.8% SUVmean reduction, 36.9% MTV reduction, and 57.8% TLG reduction. The differences in PFS and OS between groups dichotomized by these cutoffs were significant (all p < 0.01). Multivariate analysis suggested that a ΔTLG% > 57.8% was an independent postoperative risk factor for PFS (hazard ratio [HR] 0.348, 95% confidence interval [CI] 0.131-0.926, p = 0.035) and OS (HR 0.107, 95% CI 0.023-0.498, p = 0.004). Conclusions: The metabolic parameters before and after neoadjuvant chemotherapy of 18F-FDG PET/CT accurately reflected the chemotherapy effect, and ΔTLG% was the only independent postoperative predictive factor of PFS and OS for locally advanced gastric cancer.

Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway.

AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this study was to investigate whether matrine can alleviate liver injury and promote HOC differentiation into hepatocytes by suppression of Notch pathway. MAIN METHODS: We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western blotting. The effects of matrine in protecting liver in vivo were investigated in a rat Solt-Farber precancerous model. KEY FINDINGS: We found an abnormal activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was strongly associated with poor liver function in patients with cirrhosis with HCC. Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could maintain stem cell characteristics of HOCs. Matrine inhibited stem cell characteristics of HOCs, the expression of Notch pathway and HOC markers but upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous model, prophylactic application of matrine alleviated liver injury, downregulated Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. SIGNIFICANCE: Matrine could promote the differentiation of HOCs into hepatocytes by inhibiting the Notch signalling pathway and alleviate liver injury.

Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A.

BACKGROUND: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. METHODS: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. RESULTS: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. CONCLUSION: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs.

OBJECTIVE: To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS: Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS: Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION: Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver.

Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low- and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P<0.05). The findings suggested that matrine could prevent the early development of HCC-like lesions in a rat model, possibly by modulating Notch pathway activation.