Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review).

Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence­associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF­κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence­related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence­associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.

Efficacy of acupuncture as adjunct therapy for sleep disorders in Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to summarize existing clinical studies through a systematic review to explore the efficacy of acupuncture in treating sleep disorders in PD patients. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we retrieved the papers through 30 April 2023 from eight databases. The experimental group was treated with acupuncture plus conventional therapy, while the control group was treated with conventional therapy alone or combined with sham acupuncture. The sleep quality was the primary outcome. A team of researchers meticulously performed literature screening, data extraction and risk of bias assessment following the Cochrane Handbook. A meta-analysis was synthesized using Review Manager Version 5.4 software if feasible. The quality of the evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. RESULTS: A total of 973 papers were identified, with 15 papers involving 957 patients were included in this systematic review. The results showed that acupuncture interventions included manual acupuncture, electroacupuncture, moxibustion and bleeding, with 1-7 times every week implemented during 2-12 weeks. Acupuncture as an adjunct therapy compared to conventional therapy alone showed better effect in sleep quality and overall symptoms of PD. Risk of bias assessment showed deficiencies in blinding and allocation concealment. All included studies were synthesized in a meta-analysis, as the result of which, acupuncture improved PDSS scores(MD =16.57; 95% CI, 7.24-25.90; I2 = 97%) and effective rate for sleep disorders (OR = 5.91; 95% CI, 1.71-20.39; I2 = 54%); meanwhile, acupuncture reduced UPDRS scores(MD = -4.29; 95% CI, -6.54 - -2.03; I2 = 77%) and improved effective rate for PD (OR = 3.22; 95% CI, 1.81-5.72; I2 = 0%). The quality of evidence ranged from low to moderate by GRADE. CONCLUSION: This study provides initial evidence that acupuncture as an adjunct therapy might be associated with improvement of sleep disorders in PD. Due to the lack of high-quality studies, larger sample size studies with sham acupuncture groups should be conducted in future. REGISTRATION NUMBER: CRD42022364249 (PROSPERO).

Hydrochemical characteristics and genetic mechanism of porous sandstone geothermal water in northern Jinan, Shandong, China.

Porous sandstone geothermal water is an important geothermal resource, which is a low-carbon and clean resource, but lacks systematic research on a regional scale. The northern part of Jinan City is rich in geothermal resources, specifically porous sandstone thermal reservoirs. However, there is still incomplete research on the mechanism of geothermal genesis and the hydrochemical characteristics of geothermal water in porous sandstone. This study aims to address this gap by collecting 21 groundwater samples from northern Jinan and comparing their conventional ion and isotope characteristics to investigate the hydrochemical characteristics during the formation of geothermal water and uncover the genesis mechanism of porous sandstone geothermal water. The results indicate that the geothermal water is classified as Na-Cl type and Na-SO4-Cl type. The hydrochemical characteristics of geothermal water are primarily influenced by water-rock interaction and groundwater mixing. The water source primarily comes from the atmospheric precipitation in the Taiyi mountains, with an altitude of 910.75-1542.2 m.s.a.l.. The estimated temperature of the thermal reservoir ranges from 51 to 78 °C, and the depth of geothermal water circulation is estimated to be between 1316 and 2216 m. Based on the characteristics of the geothermal field, including the "cap rock, water source, heat source, reservoir, and channel," a conceptual model of the porous sandstone geothermal water flow system is proposed. This model offers novel insights into the genesis mechanism of geothermal water under similar geological conditions.

The Role of Probiotics in Managing Glucose Homeostasis in Adults with Prediabetes: A Systematic Review and Meta-Analysis.

Methods: The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Results: Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; p = 0.03; I2 = 76.13%, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (SMD -0.27; 95% CI -0.45, -0.09; p < 0.001; I2 = 0.50%, p = 0.36) and improve the levels of high-density lipoprotein cholesterol (HDL) (SMD -8.94; 95% CI -14.91, -2.97; p = 0.003; I2 = 80.24%, p < 0.001), when compared to the placebo group. However, no significant difference was observed in fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-α, and body mass index. Subgroup analyses showed that probiotics significantly reduced HbA1c in adults with prediabetes in Oceania, intervention duration of ≥3 months, and sample size <30. Conclusions: Collectively, our meta-analysis revealed that probiotics had a significant impact on reducing the levels of HbA1c and HOMA-IR and improving the level of HDL in adults with prediabetes, which indicated a potential role in regulating blood glucose homeostasis. However, given the limited number of studies included in this analysis and the potential for bias, further large-scale, higher-quality randomized controlled trials are needed to confirm these findings. This trial is registered with CRD42022358379.

T-cell dysfunction in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity.

MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.

PURPOSE: Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. RESULTS: We found that MLL4 expression was downregulated in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. CONCLUSION: Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

The preliminary evidence on the association of the gut microbiota with stroke risk stratification in South Chinese population.

Aims: This study aimed to investigate the association between the gut microbiota and the risk of stroke. Methods: Faecal samples from 60 participants in South China, including 45 individuals with risk factors for stroke and 15 healthy controls, were collected and subjected to 16S rRNA sequencing. A bioinformatics analysis was performed to characterise the gut microbial diversity and taxonomic compositions at different risk levels (low, moderate, and high) of stroke. Functional prediction and correlation analyses between the microbiota and laboratory markers were performed to explore the potential mechanisms. Results: A significant difference in beta diversity was observed between the participants from the stroke risk and healthy control groups. Linear discriminant effect size analysis revealed a large number of vascular beneficial bacteria enriched in the participants from the healthy control and low-risk groups, but a few vascular harmful bacteria were more abundant in the participants from the high-risk group than in those from the other groups. In addition, Anaerostipes, Clostridium_XlVb, and Flavonifractor, all of which belonged to the Firmicutes phylum, were enriched in the participants from the low-risk group, and their relative abundances gradually decreased as the stroke risk increased. Spearman's analysis revealed that these outstanding microbiota correlated with the levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, white blood cells, neutrophils, and carotid intima-media thickness. Conclusion: The preliminary evidence suggests that gut microbiota is associated with stroke risk. It potentially ameliorates atherosclerosis by targeting lipid metabolism and inflammation. This provides novel insights into the early screening of stroke risk and primary prevention.

Risk of Stroke Among Different Metabolic Obesity Phenotypes: A Systematic Review and Meta-Analysis.

Background and Purpose: Overweight/obesity is a modified risk factor for stroke. This systematic review and meta-analysis aimed to assess the impact of different obesity phenotypes on stroke risk in adults. Methods: The PubMed, Embase, and Cochrane Library databases were searched from their inception to 7 March 2021 to identify the prospective cohort studies investigating stroke risk among different metabolic overweight/obesity phenotypes. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of eleven prospective cohorts (n = 5,609,945 participants) were included in the systematic review, nine of which were included in the meta-analysis. All metabolically unhealthy phenotypes had a higher risk of stroke than the metabolically healthy normal-weight phenotypes, including metabolically unhealthy normal weight (HR = 1.63, 95% CI: 1.41-1.89, I2 = 89.74%, n = 7 cohort studies, 1,042,542 participants), metabolically unhealthy overweight (HR = 1.94, 95% CI: 1.58-2.40, I2 = 91.17%, n = 4 cohort studies, 676,166 participants), and metabolically unhealthy obese (HR = 1.99, 95% CI: 1.66-2.40, I2 = 93.49%, n = 6 cohort studies, 1,035,420 participants) phenotypes. However, no risk of stroke was observed in the populations with metabolically healthy overweight (MHOW) (HR = 1.07, 95% CI: 1.00-1.14, I2 = 69.50%, n = 5 studies, 4,171,943 participants) and metabolically healthy obese (MHO) (HR = 1.07, 95% CI: 0.99-1.16, I2 = 54.82%, n = 8 studies, 5,333,485 participants) phenotypes. The subgroup analyses for the MHO studies suggested that the risk of stroke increased only when the MHO participants were mainly females, from North America, and when the World Health Organization standard was applied to define obesity. In the subgroup analysis of the risk of stroke in MHOW, a longer follow-up duration was also associated with a higher risk of stroke. Conclusion: The risk of stroke increase for all metabolically unhealthy phenotypes irrespective of the body mass index (BMI). The associated risk of stroke with metabolic health but high BMI shows substantial heterogeneity, which requires future research considering the impact of sex and transition of the metabolic status on the risk of stroke. Systematic Review Registration: The study protocol was prospectively registered in PROSPERO (No. CRD42021251021).

Highly undersampling dynamic cardiac MRI based on low-rank tensor coding.

Dynamic cardiac magnetic resonance imaging (CMRI) is an important tool for the non-invasive assessment of cardiovascular disease. However, dynamic CMRI suffers from long acquisition times due to the need of obtaining images with high temporal and spatial resolution, whole-heart coverage. Conventionally, a multidimensional dataset in dynamic CMRI is treated as a series of two-dimensional matrices, and then various matrix/vector transforms are used to explore the sparsity of MR images. In this paper, we propose a low-rank tensor coding (LRTC) model with tensor sparsity for the application of compressive sensing (CS) in dynamic CMRI. In this framework, each group of 3D similar patches extracted from high-dimensional images is considered to be a low-rank tensor. LRTC can better capture the sparse part of dynamic CMRI and make full use of the redundancy between the feature vectors of adjacent positions. ADMM technique is introduced to tackle the proposed model, where soft threshold operator is used to solving the l1 norm relaxation. Higher-order singular value decomposition (HOSVD) is exploited to process high-dimensional tensors and mine correlations in space-time dimensions. Validations based on cardiac cine and myocardial perfusion datasets indicate that the proposed method achieved comparable reconstruction accuracy with the low-rank matrix recovery methods, and outperformed the conventional sparse recovery methods.

A role for the NPM1/PTPN14/YAP axis in mediating hypoxia-induced chemoresistance to sorafenib in hepatocellular carcinoma.

BACKGROUND: Tumor microenvironments are characterized by resistance to chemotherapeutic agents and radiotherapy. Hypoxia plays an important role in the development of tumor resistance, as well as the generation of metastatic potential. YAP also participates in the regulation of hypoxia-mediated chemoresistance, and is negatively regulated by protein tyrosine phosphatase non-receptor type 14 (PTPN14). METHODS: The PTPN14 expression in hepatocellular carcinoma (HCC) tissues were evaluated by qRT-PCR, western blot and tissue microarrays. The effect of PTPN14 on HCC progression was investigated in vitro and in vivo. RESULTS: Here, we report that PTPN14 expression was downregulated in HCC tissues and cell lines. Silencing PTPN14 significantly enhanced proliferation, migration, invasion of HepG2 cells in vitro and tumor growth and metastasis in vivo, whereas overexpression of PTPN14 significantly inhibited these abilities in SK-Hep1 cells. We also found that hypoxia-induced nuclear translocation and accumulation of PTPN14 led to resistance to sorafenib in HCC cells. Further mechanistic studies suggested that NPM1 regulates PTPN14 localization, and that NPM1 regulates YAP by retaining PTPN14 in the nucleus under hypoxic conditions. CONCLUSIONS: These data suggest that a therapeutic strategy against chemoresistant HCC may involve disruption of NPM1-mediated regulation of YAP by retaining PTPN14 in the nucleus under hypoxic conditions.

Construction of a novel radiomics nomogram for the prediction of aggressive intrasegmental recurrence of HCC after radiofrequency ablation.

OBJECTIVES: To construct a precise prediction model of preoperative magnetic resonance imaging (MRI)-based nomogram for aggressive intrasegmental recurrence (AIR) of hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA). METHODS: Among 891 patients with HCC treated by RFA, 22 patients with AIR and 36 patients without AIR (non-AIR) were finally enrolled in our study, and each patient was followed up for more than 6 months to determine the occurrence of AIR. The laboratory indicators and MRI features were compared and assessed. Preoperative contrast-enhanced T1-weighted images (CE-T1WI) were used for radiomics analysis. The selected clinical indicators and texture features were finally screened out to generate the novel prediction nomogram. RESULTS: Tumor shape, ADC Value, DWI signal intensity and ΔSI were selected as the independent factors of AIR by univariate and multivariate logistic regression analysis. Meanwhile, two radiomics features were selected from 396 candidate features by LASSO (P < 0.05), which were further used to calculate the Rad-score. The selected clinical factors were further integrated with the Rad-score to construct the predictive model, and the AUCs were 0.941 (95% CI: 0.876-1.000) and 0.818 (95% CI: 0.576-1.000) in the training (15 AIR and 25 non-AIR) and validation cohorts (7 AIR and 11 non-AIR), respectively. The AIR predictive model was further converted into a novel radiomics nomogram, and decision curve analysis showed good agreement. CONCLUSIONS: The predictive nomogram integrated with clinical factors and CE-T1WI -based radiomics signature could accurately predict the occurrence of AIR after RFA, which could greatly help individualized evaluation before treatment.

Reporting quality evaluation of the stroke clinical practice guidelines: a systematic review.

OBJECTIVES: To analyze the effectiveness and quality of stroke clinical practice guidelines (CPGs) published in recent years in order to guide future guideline developers to develop better guidelines. PARTICIPANTS: No patient involved METHOD: PubMed, China Biology Medicine (CBM), Wanfang, CNKI, and CPG-relevant websites were searched from January 2015 to December 2019 by two researchers independently. The RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was used to assess the reporting quality in terms of domains and items. Then, a subgroup analysis of the results was performed. PRIMARY AND SECONDARY OUTCOME MEASURES: RIGHT checklist reporting rate RESULTS: A total of 66 CPGs were included. Twice as many CPGs were published internationally as were published in China. More than half were updated. Most CPGs are published in journals, developed by societies or associations, and were evidence-based grading. The average reporting rate for all included CPGs was 47.6%. Basic information got the highest (71.7% ± 19.7%) reporting rate, while review and quality assurance got the lowest (22.0% ± 24.6%). Then, a cluster analysis between countries, publishing channels, and institutions was performed. There were no statistically significant differences in the reporting quality on the CPGs between publishing countries (China vs. international), publishing channels (journals vs. websites), and institutions (associations vs. non-associations). CONCLUSIONS: Current stroke CPGs reports are of low quality. We recommend that guideline developers improve the quality of reporting of key information and improve the management of conflicts of interest. We recommend that guideline developers consider the RIGHT checklist as an important tool for guideline development. TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/PBWUX .

KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer.

PURPOSE: Epigenetic regulation plays critical roles in cancer progression, and high-frequency mutations or expression variations in epigenetic regulators have been frequently observed in tumorigenesis, serving as biomarkers and targets for cancer therapy. Here, we aimed to explore the function of epigenetic regulators in breast cancer. METHODS: The mutational landscape of epigenetic regulators in breast cancer samples was investigated based on datasets from the Cancer Genome Atlas. The Kaplan-Meier method was used for survival analysis. RNA sequencing (RNA-seq) in MCF-7 cells transfected with control siRNA or KMT2C siRNA was performed. Quantitative reverse transcription-PCR and chromatin immunoprecipitation were used to validate the RNA-seq results. RESULTS: Among the 450 epigenetic regulators, KMT2C was frequently mutated in breast cancer samples. The tumor mutational burden (TMB) was elevated in breast cancer samples with KMT2C mutations or low KMT2C mRNA levels compared to their counterparts with wild-type KMT2C or high KMT2C mRNA levels. Somatic mutation and low expression of KMT2C were independently correlated with the poor overall survival (OS) and disease-free survival (DFS) of the breast cancer samples, respectively. RNA-seq analysis combined with chromatin immunoprecipitation and qRT-PCR assays revealed that the depletion of KMT2C remarkably affected the expression of DNA damage repair-related genes. More importantly, the low expression of KMT2C was related to breast cancer cell sensitivity to chemotherapy and longer OS of breast cancer patients who underwent chemotherapy. CONCLUSION: We conclude that KMT2C could serve as a potential biomarker of prognosis and chemotherapy sensitivity by affecting the DNA damage repair-related genes of breast cancer.

ß-Asarone Ameliorates ß-Amyloid-Induced Neurotoxicity in PC12 Cells by Activating P13K/Akt/Nrf2 Signaling Pathway.

Accumulation of ß-amyloid (Aß) causes oxidative stress, which is the major pathological mechanism in Alzheimer's disease (AD). ß-asarone could reduce Aß-induced oxidative stress and neuronal damage, but the molecular mechanism remains elusive. In this study, we used an Aß-stimulated PC12 cell model to explore the neuroprotective effects and potential mechanisms of ß-asarone. The results showed that ß-asarone could improve cell viability and weaken cell damage and apoptosis. ß-asarone could also decrease the level of ROS and MDA; increase the level of SOD, CAT, and GSH-PX; and ameliorate the mitochondrial membrane potential. Furthermore, ß-asarone could promote the expression of Nrf2 and HO-1 by upregulating the level of PI3K/Akt phosphorylation. In conclusion, ß-asarone could exert neuroprotective effects by modulating the P13K/Akt/Nrf2 signaling pathway. ß-asarone might be a promising therapy for AD.

Percutaneous biliary stent combined with brachytherapy using 125I seeds for treatment of unresectable malignant obstructive jaundice: A meta-analysis.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a common pathologic manifestation of malignant biliary obstruction. Recently, several clinical trials have explored the clinical effectiveness of intraluminal 125I seed-based brachytherapy for MOJ patients, and various outcomes have been reported. AIM: To assess the efficacy and safety of percutaneous biliary stents with 125I seeds compared to conventional metal stents in patients with unresectable MOJ. METHODS: A systematic search of English-language databases (PubMed, Embase, Cochrane Library, and Web of Science) was performed to identify studies published prior to June 2020 that compared stents with or without 125I seeds in the treatment of unresectable MOJ. The outcomes analyzed included primary outcomes (stent patency and overall survival) and secondary outcomes (complications and liver function parameters). RESULTS: Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis. Of the 875 included patients, 404 were treated with 125I seed stents, while 471 were treated with conventional stents. Unadjusted pooled analysis demonstrated that compared to conventional stents, 125I seed stents extended the stent patency time [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.28-0.45, P < 0.0001] and overall survival period (HR = 0.52, 95%CI = 0.42-0.64, P < 0.00001). Subgroup analyses based on the type of 125I seed stent and type of study design showed consistent results. However, there were no significant differences in the occurrence of total complications [odds ratio (OR) = 1.12, 95%CI = 0.75-1.67, P = 0.57], hemobilia (OR = 1.02, 95%CI = 0.45-2.3, P = 0.96), pancreatitis (OR = 1.79, 95%CI = 0.42-7.53, P = 0.43), cholangitis (OR = 1.13, 95%CI = 0.60-2.13, P = 0.71), or pain (OR = 0.67, 95%CI = 0.22-2, P = 0.47). In addition, there were no reductions in the levels of serum indices, including total bilirubin [mean difference (MD) = 10.96, 95%CI = -3.56-25.49, P = 0.14], direct bilirubin (MD = 7.37, 95%CI = -9.76-24.5, P = 0.4), alanine aminotransferase (MD = 7.52, 95%CI = -0.71-15.74, P = 0.07), and aspartate aminotransferase (MD = -4.77, 95%CI = -19.98-10.44, P = 0.54), after treatment. Publication bias was detected regarding the outcome overall survival; however, the conclusions were not changed after the adjustment. CONCLUSION: Placement of stents combined with brachytherapy using 125I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage. Thus, it can be considered an effective and safe treatment for unresectable MOJ.

Predictive value on diffusion weighted imaging scores for basilar artery occlusion after endovascular treatment.

PURPOSE: To assess the predictive value of three scoring systems based on diffusion weighted imaging in basilar artery occlusion patients after endovascular treatment. METHODS: We analyzed clinical and radiological data of patients with basilar artery occlusion from January 2010 to June 2019, with modified Rankin Scale of 0-2 and 3-6 defined as favorable outcome and unfavorable outcome at three months. Diffusion weighted imaging posterior circulation ASPECTS Score (DWI pc-ASPECT Score), Renard diffusion weighted imaging Score, and diffusion weighted imaging Brainstem Score were used to evaluate the early ischemic changes. RESULTS: There were a total of 88 basilar artery occlusion patients enrolled in the study after endovascular treatment, with 33 of them getting a favorable outcome. According to the analysis, the time from onset to puncture within 12 h (odds ratio: 4.34; 95% confidence interval: 1.55-12.16; P = 0.01), presence of collateral flow via PCoA (odds ratio: 0.31; 95%CI: 0.12-0.79; P = 0.01) or between PICA and SCA (odds ratio: 0.18; 95%CI: 0.07-0.47; P = 0.00), equal or less than 15 points on baseline NIHSS (area under the curve 0.79, 95% CI 0.69-0.89; sensitivity = 69.1%, specificity = 81.8%; P = 0.00), and equal or less than 1.5 points on diffusion weighted imaging Renard score (area under the curve 0.63, 95% CI 0.51-0.75; sensitivity = 83.6%, specificity = 39.4%; P = 0.046) were independently associated with favorable outcome. CONCLUSIONS: Renard diffusion weighted imaging score may be an independent predictor of functional outcome in basilar artery occlusion patients after endovascular treatment.

Correction to: Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

An amendment to this paper has been published and can be accessed via the original article.

The transcriptome analysis of the whole-body of the gastropod mollusk Limax flavus and screening of putative antimicrobial peptide and protein genes.

The gastropod mollusk Limax flavus, one of the most widespread pests in China, is used to treat infectious diseases in traditional Chinese medicine. However, little genomic information is available for this non-model species. In this study, the whole-body transcriptome of L. flavus was sequenced using next generation sequencing technology. A total of 6.81 Gb clean reads were obtained, which were assembled into 150,766 transcripts with 132,206 annotated unigenes. Functionally classification assigned 30,542 unigenes to 56 Gene Ontology terms, 16,745 unigenes were divided into 26 euKaryotic Ortholog Groups of proteins categories, and 13,854 unigenes were assigned to 230 Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, we identified 17,251 simple sequence repeats and several kinds of antimicrobial peptide and protein (AMPs) genes. The transcriptome data of L. flavus will provide a valuable genomic resource for further studies on this species, and the AMPs identified in L. flavus will support its medical potential.

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

BACKGROUND: Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. METHODS: Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. RESULTS: Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvß3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvß3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. CONCLUSIONS: Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC. Video Abstract.

De novo transcriptome of the whole-body of the gastropod mollusk Philomycus bilineatus, a pest with medical potential in China.

Philomycus bilineatus is a highly common gastropod mollusk pest in China and is also utilized to treat infectious diseases. However, no genomic resources are available for this non-model species. In the present study, the transcriptomic analysis of P. bilineatus was completed. After sequencing using the next generation sequencing technology, 9.11 Gb of clean reads were obtained, which led to the assembly and annotation of 145,523 transcripts and 125,690 unigenes. Unigenes were functionally classified using Gene Ontology (GO), euKaryotic Ortholog Groups of proteins (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 27,554 unigenes were assigned into 55 GO terms, 13,989 unigenes were differentiated into 26 KOG categories, and 16,368 unigenes were assigned to 229 KEGG pathways. Furthermore, 16,614 simple sequence repeats (SSRs), 38 olfactory genes, and 40 antimicrobial peptide/protein genes were identified. The transcriptome profile of P. bilineatus will provide a valuable genomic resource for further study, will promote the development of new pest management strategies through interference of chemosensory communication, and will support potential medicinal uses of this species.