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Background Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection., Graphical abstract Image 1

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis

Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

Objectives Postmenopausal osteoporosis (PMO) and osteoporotic fracture seriously impair human health in developed countries. The present study aims to explore whether sensory nerves, calcitonin gene-related peptide (CGRP), and brain-derived serotonin are related to bone loss in ovariectomized (OVX) rats. Methods Female rats were grouped into the ovariectomized (OVX) and sham surgery (SHAM) groups. Immunocytochemistry, western blotting, and qPCR were performed to detect CGRP expression in the femurs. The expression levels of serotonin and CGRP in the spinal cord and brainstem were estimated using western blotting, immunofluorescence, and qPCR. ELISA was used to evaluate the serum biomarkers of bone formation and resorption. Bone mineral density was measured using dual-energy X-ray (DXA) analysis. Femur microstructure was imaged by Micro CT. P values less than 0.05 were considered statistically significant. Results ELISA showed that serum bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), β-crosslaps, and β-ctx were increased in the OVX group. In the OVX group, in vivo bone mineral density, trabecular bone mineral density, bone volume fraction (BV/TV), and trabecular number (Tb. N) were significantly decreased, while trabecular spacing (Tb. Sp) and trabecular bone pattern factor (Tb. Pf) were markedly increased. In the OVX group, the expression levels of CGRP of the femur were significantly downregulated. In contrast, CGRP and serotonin expression was increased in the spinal cord of the OVX group. Serotonin expression was increased in the brainstem, brainstem nucleus raphe magnus (RMG), and nucleus raphe dorsalis (DRN). Conclusion Our results indicated that the activation of osteoclast triggered the release of CGRP from nociceptive sensory nerve fibers and transmitted this painful stimulus to the dorsal horn of the spinal cord to release increased CGRP. The descending serotonergic inhibitory system was activated by increased CGRP levels of the spinal cord and promoted serotonin release in the brainstem RMG, DRN, and the spinal cord, contributing to the decreased CGRP level in bone tissue, which revealed a novel mechanism of bone loss in PMO.

Hesperetin-7-O-glucoside (Hes-7-G) is a naturally occurring flavonoid monoglucoside in Citri Reticulatae Pericarpium and exhibits relatively high biological activities. To explore the anti-inflammatory capacity of dietary Hes-7-G, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and dextran sodium sulfate (DSS)-induced colitis mice were used here as in vitro and in vivo inflammation models. The results showed that Hes-7-G (5 μM) significantly restored cellular metabolic disorders and inflammation in LPS-stimulated RAW264.7 macrophages. In the in vivo study, dietary Hes-7-G (1 mg/kg body weight) markedly alleviated the inflammatory status in DSS-induced colitis mice, manifested by the recovered colon length from 5.91 ± 0.66 to 6.45 ± 0.17 cm, histopathological changes, and mRNA levels of colonic inflammatory factors including Tnf-α and Il-22. Furthermore, dietary Hes-7-G not only profoundly regulated the gut microbiota composition including phyla Bacteroidetes, Cyanobacteria, Desulfobacterota, and Deferribacteres and genus Enterorhabdus, Prevotellaceae, Gastranaerophilales, Enterococcus, Intestinimonas, Ruminococcaceae, and Eubacterium in the cecal contents but also especially adjusted the co-metabolites such as short chain fatty acids and indole metabolites (indole-3-propionic, indole acetic acid), which were markedly altered by DSS treatment in mice. These findings demonstrated that Hes-7-G has strong anti-inflammatory activity in vitro and in vivo and potential preventive or therapeutic effects for chronic inflammation diseases.

Objective Diabetes increases the risk for cancers. However, whether it is associated with hematologic malignancies is not clear. The present study investigated the association between diabetes and acute lymphocytic leukemia (ALL), acute myeloid leukemia (ML), non-Hopkin lymphoma (NHL), and multiple myeloma (MM). Methods Newly diagnosed adult cancer patients were recruited consecutively from our clinical database. Peoples from a local enterprise were recruited to create a small-scale population-based dataset. We compared the diabetes prevalence between the cancer patients and the local people; an increase in diabetes prevalence in the cancer patients suggests an association between diabetes and the cancer(s). Results We found that the prevalence of diabetes was 19.7%, 21.3%, 12.5%, and 12.0% in ALL, AML, NHL, and MM, respectively, which was higher than that (9.1%) in the local people. Despite that there were more male than female cancer patients, there were more female than male diabetic patients. The increase in diabetes prevalence occurred in ALL and NHL patients aged 18 to 39 years old as well as in AML patients over 40. In MM patients, the increase in diabetes prevalence (18.6%) occurred only in females. Approximately 70% of the diabetic patients were undiagnosed before the diagnosis of the blood cancer. Approximately half of the pre-existing diabetic patients had anti-diabetic treatment, with over 70% of them still had poor glycemic control. Conclusions Our results suggest that diabetes is associated with ALL, AML, NHL, and MM, at least in adult patients.

Purpose To investigate the potential safety and efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in treating TACE-refractory hepatocellular carcinoma (HCC). Methods We retrospectively evaluated the treatment outcomes of DEB-TACE for 41 HCC nodules in 30 patients who were refractory to conventional TACE (c-TACE) according to tumor response. The antitumor response was evaluated according to mRECIST criteria, and changes in alpha-fetoprotein (AFP), albumin-bilirubin score, the incidence of adverse events, and the time to disease progression were observed. Results The objective response rate and disease control rates were 60.98% and 95.12% at 4 weeks after DEB-TACE, 63.41% and 92.68% at 8 weeks, respectively. The median time of disease progression was 4.60 ± 0.23 months. The AFP of patients decreased continuously at 2–6 weeks after operation, and the AFP at 4 weeks was significantly lower than that at 2 weeks (P = 0.038). Adverse reactions were well tolerated, and no grade 4 adverse reactions were reported. The albumin-bilirubin score did not deteriorate within 6 weeks. Conclusion DEB-TACE has potential efficacy and safety after failure of c-TACE in patients with advanced liver cancer. Further studies are needed to confirm the efficacy of DEB-TACE treatment after failure of c-TACE.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub-pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub-pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then using Wt1tm1(EGFP/Cre)Wtp /J knock-in mice, we observed PMC migration into lung parenchyma in bleomycin-induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration. In vitro studies revealed that bleomycin and transforming growth factor-β1 increased calpain activity in PMCs, and activated calpain-mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen-I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C-terminal and N-terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin-1, and p-cofilin-1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub-pleural fibrosis in IPF.

Purpose The U.S. Department of Veterans Affairs (VA) health care system monitors time from referral to specialist visit. We compared wait times for carpal tunnel release (CTR) at a VA hospital and its academic affiliate. Methods We selected patients who underwent CTR at a VA hospital and its academic affiliate (AA) (2010–2015). We analyzed time from primary care physician (PCP) referral to CTR, which was subdivided into PCP referral to surgical consultation and surgical consultation to CTR. Electrodiagnostic testing (EDS) was categorized in relation to surgical consultation (prereferral vs postreferral). Multivariable Cox proportional hazard models were used to examine associations between clinical variables and surgical location. Results Between 2010 and 2015, VA patients had a shorter median time from PCP referral to CTR (VA: 168 days; AA: 410 days), shorter time from PCP referral to surgical consultation (VA: 43 days; AA: 191 days), but longer time from surgical consultation to CTR (VA: 98 days; AA: 55 days). Using multivariable models, the VA was associated with a 35% shorter time to CTR (AA hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.52–0.82) and 75% shorter time to surgical consultation (AA HR, 0.25; 95% CI, 0.20–0.03). Receiving both prereferral and postreferral EDS was associated with almost a 2-fold prolonged time to CTR (AA HR, 0.49; 95% CI, 0.36–0.67). Conclusions The VA was associated with shorter overall time to CTR compared with its AA. However, the VA policy of prioritizing time from referral to surgical consultation may not optimally incentivize time to surgery. Repeat EDS was associated with longer wait times in both systems. Clinical Relevance Given differences in where delays occur in each health care system, initiatives to improve efficiency will require targeting the appropriate sources of preoperative delay. Judicious use of EDS may be one avenue to decrease wait times in both systems.

This study aimed to assess health concerns after hysterectomy from different perspectives among Taiwanese women with uterine fibroids. A mixed-methods was used in this study. In a cross-sectional study, 95 patients completed a structured questionnaire (Health Concern Questionnaire-HCQ). Face-to-face interviews with 5 patients were implemented for the qualitative component from OBS-GYN outpatient departments at two hospitals in Northern Taiwan. Participants who met the following criteria, 20 years of age or older, conscious alert without mental disturbances were recruited to this study. Descriptive statistics were calculated for social demographic variables and HCQ. A content analysis was used to analyze the qualitative data. The mean age was 46.28 of 95 patients. Findings of the present study showed that the most health concerns among patients with UFs after hysterectomy are hysterectomy-related complications, follow by impacts on daily life, body image and female identity, and intimacy and sexual relations. The findings of qualitative interviews supported the above findings. In addition, the information needs of post-operative self-care were identify in this qualitative interviews. The results of this research study could help healthcare professionals to address women's health concerns and provide adequate care for Taiwanese women with uterine fibroids after hysterectomy.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson’s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.

Oncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear. Here we use Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. These findings suggest that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients., Dong, Vadla et al. find that oncogenic Ras and p53 cooperatively stimulate JAK/STAT cytokines to promote non-autonomous tissue overgrowth in Drosophila. Further, blocking STAT signalling prevents the growth-inducing effect of p53 overexpression and ionising irradiation in human cancer lines in culture and in mouse xenografts, suggesting a therapeutic route.

Background The aim of the present study was to identify key genes and pathways downstream of S100PPBP in pancreatic cancer cells. Methods The microarray datasets GSE35196 (S100PBP knockdown) and GSE35198 (S100PBP overexpression) were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were obtained separately from GEO2R, and heatmaps showing clustering analysis of DEGs were generated using R software. Gene Ontology and pathway enrichment analyses were performed for identified DEGs using the Database for Annotation, Visualization, and Integrated Discovery and Kyoto Encyclopedia of Genes and Genomes, respectively. A protein-protein interaction (PPI) network was created using the Search Tool for the Retrieval of Interacting Genes and Cytoscape software. Relevant expression datasets of key identified genes were downloaded from The Cancer Genome Atlas, and overall survival (OS) analysis was performed with R software. Finally, Gene Expression Profiling Interactive Analysis was used to evaluate the expression of key DEGs in pancreatic cancer tissues. Results A total of 34 DEGs (11 upregulated and 23 downregulated) were screened out from the two datasets. Gene Ontology enrichment analysis revealed that the identified DEGs were mainly functionally enriched in ATPase activity, production of siRNA involved in RNA interference, and production of miRNAs involved in gene silencing by miRNA. The pathway enrichment analysis of the identified DEGs showed enrichment mainly in apoptosis, non-homologous end-joining, and miRNA pathways in cancer. The protein–protein interaction network was composed of 21 nodes and 30 edges. After survival analysis and gene expression analysis, 4 genes associated with poor prognosis were selected, including LMNB1, PRKRA, SEPT2, and XRCC5. Conclusions LMNB1, PRKRA, SEPT2, and XRCC5 could be key downstream genes of the S100PBP gene in the inhibition of pancreatic cancer cell adhesion.

Background A proportion of lung cancers show sodium/iodide symporter (NIS) expression. Lung cancers with NIS expression may uptake radioiodine (RAI) and show RAI-avid lesions on RAI scan for differentiated thyroid cancer (DTC) surveillance. Aim To investigate the possibility of RAI uptake by lung cancer in a cohort with thyroid cancer. Methods RAI-avid lung cancers were analyzed using a prospectively maintained database of patients with thyroid cancer who were registered at a medical center between December 1, 1976 and May 28, 2018. NIS expression in lung cancer was assessed using immunohistochemical staining. Results Of the 5000 patients with thyroid cancer from the studied dataset, 4602 had DTC. During follow-up, 33 patients developed primary lung cancer. Of these patients, nine received an iodine-131 (131I) scan within 1 year before the diagnosis of lung cancer. One of these nine lung cancers was RAI-avid. NIS expression was evaluated, and three of the eight available lung cancers revealed NIS expression. The proportions of lung cancer cells with NIS expression were 60%, 15%, and 10%. The RAI-avid lung cancer had the highest level of expression (60%). The RAI-avid lung cancer had a spiculated border upon single-photon emission computed tomography/computed tomography, which led to an accurate diagnosis. Conclusion A proportion of lung cancer demonstrates NIS expression and is RAI-avid. Clinicians should be aware of this possibility in the interpretation of RAI scintigraphy.

Background This study aimed to identify potential stemness-related targets in gastric cancer (GC) in order to support the development of new treatment strategies and improve patient survival. Methods Using the edgeR package, we identified stemness-related differentially expressed genes (DEGs) using GSE112631 and the stemness-related signaling pathways in the Gene Set Enrichment Analysis (GSEA) database. Lasso-penalized Cox regression analysis and multivariate Cox regression analysis tested by Akaike Information Criterion (AIC) were used to screen out survival genes in order to construct a prognostic model. We verified the accuracy of our prognostic model using a nomogram and receiver operating characteristic (ROC) curve analysis. Patients were divided into two groups based on the median risk score, and functional enrichment analysis was used to explore the differences between the two groups. Results Eight genes were selected to establish a prognostic model of The Cancer Genome Atlas (TCGA) and a validation model of the GSE84437 dataset from the Genome Expression Omnibus (GEO). In both models, we found that the low risk score group had better overall survival (OS) than the high-risk score group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two risk groups were totally different. Conclusions We used eight stemness-related genes to build a prognostic model. The high-risk score group had a worse prognosis compared to the low-risk score group.

Neurosurgical procedures often cause damage to the brain tissue at the periphery from surgical manipulations. Especially during retraction, a large amount of pressure could be applied on the brain surface, which can damage it, leading to brain herniation, which can be fatal for patients. To resolve this issue, we have developed a pressure sensor that can be used to monitor the applied pressure during surgery for intraoperative care. This device was tested on a rodent model to create a superficial surgically induced damage profile for three different applied pressures (30, 50, and 70 mmHg) and compared to a standard intracranial pressure monitoring system. Magnetic resonance imaging has been performed after surgical procedures to detect the herniation caused by applied pressure. To evaluate the damage to brain cells and tissue rupture, histological analysis was performed using hematoxylin and eosin staining. A scoring system was developed to understand the severity of the surgically induced brain injury, which will help neurosurgeons to limit the pressure to an optimum point without causing damage.

In our previous study, the anticancer effect of the active fucoidan (JHCF4) isolated from acid-processed Sargassum fusiformis was evaluated. In this study, the liver-protective effects of JHCF4 against ethanol-induced Chang liver cell damage and apoptosis-related responses were investigated. Furthermore, the low cytotoxicity and high cell viability of JHCF4 against ethanol-induced cell damage, as well as its protective effect against ethanol-induced cell apoptosis, were observed via nuclear staining with Hoechst 33342 in Chang liver cells. Additionally, the treatment of the 72 h post-fertilization (hpf) zebrafish model with JHCF4 increased the ethanol-stimulated survival rates as well as decreased oxidative stress, lipid peroxidation, and cell death levels. JHCF4 was found to significantly decrease steatosis production in the 128 hpf zebrafish model by Oil Red O staining, as well as attenuate the malondialdehyde and increase the glutathione contents, compared with the untreated group. These results demonstrate that JHCF4 has a potential hepato-protective effect against ethanol-induced damage both in vitro and in vivo.

Introduction Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan, and radiation therapy combined with or without chemotherapy is its mainstay treatment. Although it is highly sensitive to radiotherapy, local recurrence and distant metastasis remain difficult unsolved problems. In recent years, graphene oxide (GO) has been found to be a promising novel anticancer drug carrier. Here, we present our designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as a drug carrier, which was loaded with erlotinib and showed promising anticancer effects on NPC cells. Methods The effects of GO-PEG-erlotinib on the proliferation, migration, and invasion of NPC cells were investigated by WST-8 assay, wound healing assay, and invasion assay, respectively. RNA sequencing was conducted and analyzed to determine the molecular mechanisms by which GO-PEG-erlotinib affects NPC cells. Results Our results showed that GO-PEG-erlotinib reduced NPC cell viability in a dose-dependent manner and also inhibited the migration and invasion of NPC cells. The RNA sequencing revealed several related molecular mechanisms. Conclusion GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be a potential therapeutic agent for treating NPC in the future.

To investigate the changes of blood pressure (BP) on patients with obstructive sleep apnea/hypopnea syndrome (OSA) before and after upper airway surgery.Case series with chart review.Tertiary academic medical center.Patients with OSA who underwent upper airway surgery were enrolled. We retrospectively investigated the nighttime and daytime BP before and at least 3 months after OSA surgery. PairedIn total, 176 patients with OSA (149 men, 27 women; mean age, 42.9 years; mean apnea/hypopnea index, 43.1/h) were enrolled in this study. The overall nighttime and daytime BP decreased significantly before and after OSA surgery (daytime systolic BP was reduced from 137.3 ± 14.0 mm Hg to 132.7 ± 17.0 mm Hg,Surgical modifications of the upper airways for patients with OSA could benefit blood pressure.

Background This report presents the third case of trochlear schwannoma arising from the pineal region and the first case to be resected using a paramedian infratentorial supracerebellar approach. Schwannomas of cranial nerves have traditionally been thought to arise from the transitional point where the axonal envelopment switches from glial cells to Schwann cells; however, recent temporal bone histopathologic evidence from vestibular schwannomas challenges this view. Of the 38 cases of pathology-confirmed trochlear schwannoma in the literature, there are only 2 cases arising from the pineal region, where the nerve sheath transition zone is located. Here, we discuss an unusual case of trochlear schwannoma arising from this transition zone. Case Description A 65-year-old man was admitted to our institute after a traffic accident. He complained of headache and dizziness, and a computed tomography scan revealed an isodense mass in the pineal region with obstructive hydrocephalus. Magnetic resonance imaging with contrast showed an enhancing mass in the pineal region. The tumor was subtotally resected using a paramedian infratentorial supracerebellar approach, and pathology confirmed the diagnosis of trochlear schwannoma. Conclusions Trochlear schwannoma should be considered when a mass is identified in the pineal region. This diagnosis should still be entertained for mass lesions along the free tentorial edge because the tumor may arise distant from the glial-Schwann transition zone located by the dorsal midbrain. We propose a treatment algorithm for this rare tumor that seeks to maximize functional outcome.

Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.Acr-dG levels were statistically correlated with CKD stages in UC patients (P0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P0.005).These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. A nationwide database of HCC patients with PVTT who underwent liver resection with ‘curative’ intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (

Aims and objectives The primary aim of this study is to explore the influence of obesity, healthy lifestyle and sleep quality of endometrial cancer survivors on their fatigue level. Background As many as 30% of endometrial cancer survivors still suffer from fatigue 5 years after completing therapy. Fatigue may hinder cancer survivors from participating in daily activities or returning to their original roles and functions, thus affecting their health-related quality of life. Design This study adopted a cross-sectional correlational research design. The STROBE checklist for cross-sectional studies was used as a reference for reporting the study. Methods A consecutive sample of 134 endometrial cancer survivors was recruited from the outpatient clinics of a medical centre in Taipei, Taiwan. Data were collected using structured questionnaires. Results Study subjects scored 44 points (SD = 7.09) on average for the fatigue levels. Results of linear regression showed that sleep quality (s = -0.38), comorbidity index (s = -0.024) and age (s = 0.20) were important predictors of fatigue. However, differences in obesity, vegetable and fruit intake, physical activity did not lead to significant differences in fatigue level. Conclusions Survivors who had poorer sleep quality, higher comorbidity index and younger age reported higher fatigue. Relevance to clinical practice The study findings are relevant for assessing and preventing fatigue in endometrial cancer survivors. Those with poorer sleep quality, higher comorbidity index and younger age are at a greater risk for fatigue and deserve further attention. Although the study results failed to support the link between obesity, vegetable and fruit intake, physical activity and fatigue, the ratio of survivors who comply with recommended healthy lifestyles was low. Hence, it is of urgent necessity that this population receives the help to maintain a healthy lifestyle.

New antimicrobial agents are urgently needed to address the emergence of multi-drug resistant organisms, especially those active compounds with new mechanisms of action. Based on the molecular structures of the FtsZ inhibitors reported, a variety of thiazole-quinolinium derivatives with aliphatic amino and/or styrene substituents were synthesized from benzothiazolidine derivatives. In the present study, to further explore the antibacterial potential of thiazole-quinolinium derivatives, several Gram-positive and Gram-negative bacteria were treated with the newly modified compounds and the biological effects were studied in detail in order to understand the bactericidal action of the compounds. Our findings reveal that some of these derivatives possess good potent bactericidal activity as they can inhibit Gram-positive methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and also some Gram-negative organisms and NDM-1 Escherichia coli. Furthermore, compounds 4a1–4a4 and 4b1–4b4 altered the morphology of bacterial cells and the cells displayed a more-elongated shape compared to the untreated cells. Biochemical assays showed that 4a4 and 4b4 stimulate FtsZ polymerization in bacterial cells, which eventually disrupts its dynamic assembly and Z-ring formation. The inhibition of this crucial step in bacterial cell division could potentially represent their main mechanism of antibacterial activity. Cytotoxicity assay and hemolysis assay suggested that 4a4 and 4b4 possess low cytotoxicity. In summary, these results further highlight the importance of 4a4 and 4b4 that could be developed as potent and effective bacteriostatic agents against multi-drug resistant bacteria.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy. However, current MSI identification methods are not available for all patients. We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation. Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC). We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction. The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation. Results: The EPLA model achieved an area-under-the-curve (AUC) of 0.8848 (95% CI: 0.8185-0.9512) in the TCGA-COAD test set and an AUC of 0.8504 (95% CI: 0.7591-0.9323) in the external validation set Asian-CRC after transfer learning. Notably, EPLA captured the relationship between pathological phenotype of poor differentiation and MSI (P < 0.001). Furthermore, the five pathological imaging signatures identified from the EPLA model were associated with mutation burden and DNA damage repair related genotype in the genomic profiles, and antitumor immunity activated pathway in the transcriptomic profiles. Conclusions: Our pathomics-based deep learning model can effectively predict MSI from histopathology images and is transferable to a new patient cohort. The interpretability of our model by association with pathological, genomic and transcriptomic phenotypes lays the foundation for prospective clinical trials of the application of this artificial intelligence (AI) platform in ICB therapy.

Oleanolic acid is an analogue of pentacyclic triterpenoids. It has been used as a hepatic drug for over 20 years in China. Currently, there are only five approved drugs derived from pentacyclic triterpenoids, including oleanolic acid (liver diseases), asiaticoside (wound healing), glycyrrhizinate (liver diseases), isoglycyrrhizinate (liver disease) and sodium aescinate (hydrocephalus). To understand more about the bioactivity and functional mechanisms of oleanolic acid, it can be developed as a potent therapeutic agent, in particular, for the prevention and treatment of heart diseases that are the leading cause of death for people worldwide. The primary aim of this mini-review is to summarize the new applications of oleanolic acid and its derivatives as cardioprotective agents reported in recent years and to highlight their therapeutic perspectives in cardiovascular diseases.

BACKGROUND Intraperitoneal (IP) chemotherapy is often a preferred treatment for ovarian cancer because of its clinical benefits, but research on the experiences of patients receiving IP chemotherapy is limited. OBJECTIVES The purpose of this article is to explore the lived experiences of Taiwanese patients diagnosed with ovarian cancer who have received at least one cycle of IP chemotherapy. METHODS A semistructured interview guide was used to collect data. Interviews were analyzed using a qualitative content analysis. FINDINGS The following themes emerged from the data.

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified to facilitate osteogenic differentiation and bone formation both in vitro and in vivo. However, whether lack of PACAP is associated with osteoporosis (OP) still remains unknown. The scope of the current study was to examine the potential relationship between serum PACAP concentrations and disease severity in female patients with postmenopausal osteoporosis (PMOP). 123 PMOP females were enrolled in our study. During the same period, BMI and age-matched 120 postmenopausal non-osteoporotic (PMNOP) patients were also recruited as control. Serum PACAP concentrations were determined by Sandwich ELISA. Bone mineral density was examined by dual-energy x-ray absorptiometry (DXA) at the total hip, lumbar 1–4 vertebrae and left femoral neck. Genant grade was utilized for evaluating the degree of vertebral fracture and receiver operating characteristic (ROC) curve was performed to examine the diagnostic value of PACAP with regard to Genant grade. The numerical rating scale (NRS) was applied for test pain and 6-min walking as well as sit-to-stand test was used for functional status. The bone turnover markers including N-terminal propeptide of type I procollagen (PINP) (marker of bone formation) and C-telopeptide of type I collagen (CTX-I) (marker of bone resorption) were also examined. The PMOP women had significantly decreased mean serum PACAP levels in comparison with the PMNOP females. Serum levels of PACAP in vertebrae fracture patients were significantly lower than that in non-fracture patients Serum PACAP concentrations were negatively and significantly related to Genant grade as well as BMD at total hip, lumbar 1–4 vertebrae and left femoral neck. Further ROC analysis indicated that PACAP may act as a decent marker for Genant grade. In addition, serum PACAP levels were negatively associated with NRS and positively related to 6-min walking as well as sit-to-stand test scores. Last, we found PACAP were negatively correlated with increased CTX-I levels and positively related to PINP levels. Attenuated PACAP concentrations were related to disease severity of PMOP, PACAP may act as a protective role during PMOP.

Background: Angiotensin receptor neprilysin inhibitor (ARNI) was recommended by major guidelines as the frontline therapy for heart failure with reduced ejection fraction (HFrEF) since its clinical benefit was proved in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. However, little is known about its safety and effectiveness in real-world practice, often with sicker and more fragile patients. In addition, East Asia population is underrepresented in PARADIGM-HF trial. Methods: We performed a retrospective analysis of patients who received ARNI in 3 medical institutes located in Northern Taiwan. Patients who received a prescription of at least 30 days of ARNI were enrolled. The date of first prescription was defined as the index date, and a period of 12 months preceding the index date was defined as the baseline period. Results: A total of 452 patients were identified (age: 61.9 ± 15.0, male: 79.4%). Compared to PARADIGM-HF populations, our patients had higher values of baseline serum creatinine (mean: 1.5 vs 1.1 mg/dL) and B-type natriuretic peptide (BNP; median: 554.5 vs 255 pg/mL). After 12 months, 41.6% of the patients received less than half of the standard dose. Overall, all-cause death, cardiovascular death, and heart failure readmission rate were 3.0%, 1.1%, and 6.9% in 12 months, respectively. In those who had both baseline and 12-month data, renal function did not change (1.7-1.8 mg/dL, P = .091), left ventricular ejection fraction improved (30.8%-36.8%, P < .001), BNP decreased (777.0-655.8 pg/mL, P = .032), and uric acid decreased (7.5-7.1 mg/dL, P = .009). Conclusion: In our study, patients with HFrEF had higher BNP and serum creatinine level at baseline and had received lower dose of ARNI than the PARADIGM-HF populations. Angiotensin receptor neprilysin inhibitor appeared to be safe as regard renal function and effective in real-world practice. Left ventricular reverse remodeling was observed 1 year after heart failure medication treatment, including ARNI.

The rising tuberculosis (TB) incidence has become one of the main health issues in the world. The objective of this study is to understand TB knowledge and what factors may predict students’ TB knowledge among University students in Indonesia. This study included a total of 200 students. Convenient sampling was used to recruit students for the study. Univariate analysis utilized, such as t-test and one-way ANOVA and Pearson correlations coefficient. Stepwise multiple regression analysis was used to understand which factors can predict the TB knowledge. Overall, the mean score for TB knowledge among the students was 9.49 out of 14. Most of the respondents were male, and included several ethnicities, such as Sunda and non-Sunda. The variables associated with TB knowledge were gender, education, major field of study, and heard of TB. Moreover, the study found that, as predictors, the variables that influenced knowledge about TB ranked according to relevance were: major field of study and educational background. Health promotion among students is very important to improve their knowledge related to TB disease. The findings could be used for designing the university strategic programs in measuring the knowledge of TB among their students. Students with accurate knowledge of TB can help reduce its prevalence in Indonesia.

BackgroundProstate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease.MethodsA total of 412 men with PSA of 2–20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound.ResultsOf the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15–1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p=0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting.ConclusionThe PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa.

Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid–binding protein 4 (FABP4) and sterol regulatory element–binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.

IntroductionProspective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort study in southern China.MethodsBased on an NPC screening cohort established in 2008–2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30–69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation.ResultsDuring a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15–0.62) for the highest intake frequency and 0.29 (95% CI: 0.16–0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65–0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64–0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59–0.84) for VCA-IgA and 0.64 (95% CI: 0.54–0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals.ConclusionsWith inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas.

Longitudinal trends on traumatic cataract wound dehiscence are scant. In this study, we present the characteristics of traumatic cataract wound dehiscence using 15 years of longitudinal trend in one of the largest medical centers in Taiwan for a period when cataract surgeries were gradually shifting from extracapsular cataract extraction (ECCE) to phacoemulsification. All patients with a prior cataract surgery who suffered from blunt open globe trauma between 2001 and 2015 at a tertiary referral center in Taiwan were included. The number of cases per year; type of prior cataract surgery; visual acuity (VA); mechanism and place of injury were analyzed. The risk factors associated with final VA were investigated in patients followed up for ≥ 1 month. Seventy-six eyes of 75 patients were included and all of them were traumatic cataract wound dehiscence with a prior ECCE (65 eyes) or phacoemulsification. The most common mechanism and place of injury was fall and at home in both cataract surgical types. The mean log of the minimal angle resolution (logMAR) of final VA was 2.15 ± 0.88 (ECCE) and 1.61 ± 0.83 (phacoemulsification) (P = .026). The most significant risk factors associated with worse final VA were retinal detachment at the initial visit and low ocular trauma score (both P

INTRODUCTION AND OBJECTIVE:Mineralcorticoid receptor antagonist was the first-line treatment in bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA). Some patients were refractory to...

The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the "microbiota-gut-brain" axis. The aims of this study were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundances of commensal microbes in the families Lachnospiraceae and Prevotellaceae, which were significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. Regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolite alteration might be a cofactor for developing of alcohol dependence. IMPORTANCE Gut microbiota dysbiosis is associated with certain psychiatric disorders through the "microbiota-gut-brain" axis. Here, we revealed that alcohol consumption induced colonic microbiota dysbiosis, increased intestinal permeability, and altered the serum metabolic phenotype in rats, and there was a strong correlation between gut microbiota dysbiosis and serum metabolite disorders. Thus, gut microbiota dysbiosis and serum metabolite alteration may be a cofactor for development of alcohol dependence.

A 2D monocular endoscope has been used in transcanal transpromontory vestibular schwannoma surgery instead of craniotomy. However, the absence of depth perception is the limitation of this approach. With the loss of depth perception, the surgeon will be not able to perform delicate and particularly complicated surgery. A binocular endoscope has been developed to provide stereoscopic vision with better depth perception for complicated anatomic structures and has been applied in some endoscopic surgeries. However, the diameter of the endoscope is a limitation in the performance of transcanal otologic surgeries. A small diameter endoscope facilitates easier surgery in a restricted space. A computer-based 3D imaging system can obtain 3D images in real-time using a small monocular endoscope. In this study, to evaluate the feasibility of a computer-based 3D imaging system for endoscopic lateral skull base surgery, we applied this 3D imaging system in a transcanal transpromontorial approach in two patients with vestibular schwannomas. The surgical procedure was completed without complication in these two cases. There was no mortality, perioperative complications, nor notable postoperative complications. Using this computer-based 3D imaging system, a better depth perception and stereoscopic vision was observed compared to a conventional 2D endoscope. The improvement in depth perception offers superior management of the complicated surgical anatomy.

Vertebro–venous fistula (VVF) refers to an abnormal arteriovenous shunt connecting the extracranial vertebral artery and the paraspinal venous structures. Coil embolization is the mainstay treatment of choice for VVF, and accurate definition of the endovascular target is mandatory. Traditionally, catheter-based angiograms are used for treatment planning, but those images lack bony information to delineate the precise relationship of the drainage veins to the spinal structure. Herein, we presented two VVF cases and demonstrated how we used intra-arterial cone-beam computed tomography angiography (IA-CBCTA) to determine the safe embolization zone for dense coil packing. We propose that IA-CBCTA is a useful adjunct in the endovascular planning of VVF by offering an image consisting of bony and vascular information.

Simple Summary Adavosertib is a first-in-class Wee1 inhibitor that has demonstrated activity against certain cancers. We evaluated the effects of adavosertib in treating differentiated thyroid cancer (DTC) using four DTC cell lines (BHP7-13, K1, FTC-133, FTC-238). Adavosertib accumulated cells in the G2/M phase and induced apoptosis in four DTC cell lines. Baseline Wee1 levels correlated with adavosertib sensitivity. Single-agent adavosertib therapy was sufficient to inhibit the growth of K1 and FTC-133 tumor models. Adavosertib potentiated the anti-tumor effect of dabrafenib and trametinib in K1 xenografts harboring the BRAFV600E mutation, with promising safety profiles. Adavosertib also improved the anti-tumor efficacy of lenvatinib in FTC-133 xenografts. Our results suggest the clinical efficacy of adavosertib for DTC patient therapy. Abstract Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in four DTC cell lines. Adavosertib induces cell growth inhibition in a dose-dependent fashion. Cell cycle analyses revealed that cells were accumulated in the G2/M phase and apoptosis was induced by adavosertib in the four DTC tumor cell lines. The sensitivity of adavosertib correlated with baseline Wee1 expression. In vivo studies showed that adavosertib significantly inhibited the xenograft growth of papillary and follicular thyroid cancer tumor models. Adavosertib therapy, combined with dabrafenib and trametinib, had strong synergism in vitro, and revealed robust tumor growth suppression in vivo in a xenograft model of papillary thyroid cancer harboring mutant BRAFV600E, without appreciable toxicity. Furthermore, combination of adavosertib with lenvatinib was more effective than either agent alone in a xenograft model of follicular thyroid cancer. These results show that adavosertib has the potential in treating DTC.

Simple Summary To improve the use of hydrophobic photosensitizer IR-780 in photothermal/photodynamic therapy (PTT/PDT), we entrap IR-780 within the lipid bilayer of liposomes (ILs). Compared to free IR-780, ILs showed well-preserved photothermal response by maintaining the photostability of IR-780 from repeated near infrared (NIR) laser exposure both in vitro and in vivo. Combined with fast endocytosis by human glioblastoma cells, ILs demonstrated enhanced cytotoxicity and induced higher cell apoptosis rate toward human glioblastoma cells over free IR-780, due to PTT with overexpression of heat shock protein and PDT with generation of intracellular reactive oxygen species. To overcome the blood–brain barrier, we used convection enhanced delivery (CED) for specific delivery of ILs to brain tumors in intracranial glioma xenograft. Upon three successive NIR laser irradiations, the liposomal IR-780 could significantly improve the anti-cancer efficacy in glioma treatment, leading to diminished intracranial tumor size and prolonged animal survival time. Abstract As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. The cationic nature of ILs promotes fast endocytosis of liposomal IR-780 by U87MG human glioblastoma cells within 30 min. For PTT/PDT in vitro, ILs treatment plus NIR laser irradiation leads to overexpression of heat shock protein 70 and generation of intracellular reactive oxygen species by U87MG cells, resulting in enhanced cytotoxicity and higher cell apoptosis rate. Using intracranial glioma xenograft in nude mice and administration of ILs by convection enhanced delivery (CED) to overcome blood-brain barrier, liposomal IR-780 could be specifically delivered to the brain tumor, as demonstrated from fluorescence imaging. By providing a highly stable liposomal IR-780, ILs significantly improved anti-cancer efficacy in glioma treatment, as revealed from various diagnostic imaging tools and histological examination. Overall, CED of ILs plus successive laser-assisted PTT/PDT may be an alternative approach for treating brain tumor, which can retard glioma growth and prolong animal survival times from orthotopic brain tumor models.

Background: Ventilator dependence (VD) has been considered as a serious complication in critically ill patients in the intensive care unit (ICU). Acute kidney injury (AKI) is associated with VD as a result of lung–kidney interaction. The aim of our study was to investigate novel biomarkers in predicting ventilator dependence in critically ill surgical patients. Methods: Patients who were admitted to surgical ICU were enrolled and their serum and urine samples were collected. Novel biomarkers including gelatinase-associated lipocalin (NGAL), calprotectin, kidney injury molecule-1 (KIM-1), cystatin C, and growth differentiation factor 15 (GDF-15) were analyzed and correlated with clinical outcome. Results: A total of 33 patients were enrolled and analyzed. The majority of them received abdominal surgery prior to ICU admission. Thirteen patients were classified into the VD group, while the remaining 20 were in a non-ventilator dependence group (nVD). Statistical analysis demonstrated that the following were significantly higher in the VD group than in the nVD group: serum NGAL (420.25 ± 45.18 ng/mL vs. 314.68 ± 38.12 ng/mL, p-value 0.036), urinary NGAL (420.87 ± 41.08 ng/mL vs. 250.84 ± 39.45 ng/mL, p-value 0.002), SOFA score (11.3 ± 1.5 vs. 5.6 ± 0.7, p-value 0.001), and APACHE II score (23.2 ± 2.6 vs. 13.6 ± 0.8, p-value 0.001). The area under the ROC curve (AUROC) of urinary NGAL for VD was 0.808. The combination of urinary NGAL and SOFA score could further increase AUROC for VD to 0.835. Conclusions: The current study demonstrated the predictive capability of urinary NGAL for ventilator dependence among critically ill surgical patients. When combined with SOFA score, the predictive ability was further augmented. Further large-scale studies are warranted to validate our findings.

The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from Taiwan’s National Health Insurance Research Database. We compared these patients with control subjects matched for age, gender, history of cardiovascular disease (CVD), hyperlipidemia, diabetes mellitus, hypertension, and occupation to assess the risk of overall mortality and cause-specific mortality. Finally, our cohort comprised 30,778 patients with thyroid cancer. Three hundred and ninety-eight deaths (1.29%) occurred during a median follow-up of 60.0 months (range: 30.3 to 117.6 months). The primary cause of death was thyroid cancer mortality (31.2%), followed by other malignancy-related mortality (29.9%) and CVD mortality (12.3%). The overall mortality risk was similar between the thyroid cancer and control groups (unadjusted hazard ratio (HR): 0.98, 95% confidence interval (CI): 0.88–1.10), the adjusted HR was 1.07 (95% CI: 0.95–1.20) after multivariate adjustment for age, gender, history of CVD, hyperlipidemia, diabetes mellitus, hypertension, and occupation. The risk of other malignancy-related mortality was comparable between two groups. CVD mortality risk was lower in the thyroid cancer group, with an unadjusted HR of 0.51 (95% CI: 0.38–0.69) and adjusted HR of 0.56 (95% CI: 0.42–0.76). In conclusion, patients with thyroid cancer had excellent overall survival. Thyroid cancer-specific mortality was the leading cause of death, highlighting the importance of thyroid cancer management. Thyroid cancer patients had lower CVD mortality risk than the general population.

Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the concentrations and temporal dynamics of different hemoglobin types. However, the dynamics of the light absorption (photoplethysmography; PPG) have not been applied to survey penile hemodynamics and erection quality. This paper compared the use of photoplethysmography (PPG) to study vascular ED with standard penile Doppler ultrasonography. Men diagnosed with vascular ED for at least 6 months and nominated for penile ultrasonography were included. PPG signals were collected during the ultrasound examination. All beat-to-beat PPG waveforms were aligned with the peak and averaged to one representative template waveform for feature analysis, including amplitude differences (APD) index, reflection time index (RTI), augmentation index (AI), and perfusion index (PI). An inverse correlation was found between end-erection amplitude and both erection hardness score (EHS) and resistive index (RI). APD index and EHS as well as the international index of erectile function-5 (IIEF) and RI were positively correlated. RTI and AI were inversely correlated to IIEF and RI. PI was positively correlated to RI. PPG may therefore be useful as a noninvasive, convenient, technique for sexual function evaluation.

Wee1 is a kinase that regulates the G2/M progression by the inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic thyroid cancer was evaluated in this study. Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy showed significant retardation of the growth of two anaplastic thyroid cancer tumor models. The combination of adavosertib with dabrafenib and trametinib revealed strong synergism in vitro and demonstrated robust suppression of tumor growth in vivo in anaplastic thyroid cancer xenograft models with BRAFV600E mutation. The combination of adavosertib with either sorafenib or lenvatinib also demonstrated synergism in vitro and had strong inhibition of tumor growth in vivo in an anaplastic thyroid cancer xenograft model. No appreciable toxicity appeared in mice treated with either a single agent or combination treatment. Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury.

As important signal metabolites within enterohepatic circulation, bile acids (BAs) play a pivotal role during the occurrence and development of diet-induced nonalcoholic fatty liver disease (NAFLD). Here, we evaluated the functional effects of BAs and gut microbiota contributing to sucralose consumption-induced NAFLD of mice. The results showed that sucralose consumption significantly upregulated the abundance of intestinal genera Bacteroides and Clostridium, which produced deoxycholic acid (DCA) accumulating in multiple biological matrixes including feces, serum, and liver of mice. Subsequently, elevated hepatic DCA, one of the endogenous antagonists of the farnesol X receptor (Fxr), inhibited hepatic gene expression including a small heterodimer partner (Shp) and Fxr leading to sucralose-induced NAFLD in mice. Dietary supplements with fructo-oligosaccharide or metformin markedly restored genera Bacteroides and Clostridium abundance and the DCA level of sucralose-consuming mice, which eventually ameliorated NAFLD. These findings highlighted the effects of gut microbiota and its metabolite DCA on sucralose-induced NAFLD of mice.

The purpose of this study was to test the feasibility of utilizing the established perimenopausal fatigue self-management scale (P-MFSMS) to evaluate perimenopausal Taiwanese women’s vulnerability to fatigue syndrome. A cross-sectional study design was adopted to survey 220 perimenopausal Taiwanese women with a mean age of 51.8 ± 4.64 years and a mean body mass index of 23.07 ± 3.04 kg/m2, 75.9% of whom were married, 52.3% had a college education or above, 80.4% had salaries, 81.3% had small families, and 96.4% were not using hormone therapy. The P-MFSMS consists of 25 questions based on six categories: (1) strive to maintain work energy and efficiency, (2) seek self-help from medical resources (doctor shopping), (3) strive to maintain the normal operation of the family (seeking help and support from family or significant other), (4) make time for activities or exercise in busy life, (5) slow down or adjust lifestyle, (6) frustration. For all of these six categories, the minimum loading of each question on the factor was calculated to be over 0.50, with a Cronbach’s α of 0.78 and a corrected total-item correlation of &gt, 0.50. The goodness of fit of the model was determined to be acceptable, with a chi-square/df value of &lt, 3.0 (χ2 = 503.45 and df = 260), a root mean square error of approximation (RMSEA) value of 0.065 (&lt, 0.08), as well as a Kaiser–Meyer–Olkin (KMO) value of 0.892. The Tucker–Lewis index (TLI = 0.91), Comparative Fit index (CFI = 0.92), and Incremental Fit index (IFI = 0.92) were all &gt, 0.90. There was no statistically significant difference in the difficulty between perimenopausal and postmenopausal women utilizing differential item function (DIF) analysis. Taken together, the 25-question P-MFSMS may be a potentially valid and reliable instrument for suitably evaluating perimenopausal Taiwanese women’s vulnerability to fatigue syndrome. Future studies will be conducted to test the effectiveness of the P-MFSMS for evaluating perimenopausal Taiwanese women’s vulnerability to fatigue syndrome in clinical practice.

Objective: Though living donor liver transplantation (LDLT) is commonly performed for pediatric patients with biliary atresia (BA), pulmonary hypertension (PH) is seldom encountered or reported previously. The aim of this study is mainly to identify the prevalence of PH in pediatric patients undergoing liver transplantation and assess whether PH significantly augment the operative risk and evaluate the outcomes in this series of patients. Design: Retrospectively cohort study. Setting: Renji hospital, Shanghai, China. Participants: This study comprised 161 pediatric patients undergoing LDLT. Interventions: Patient diagnosed of PH in preoperative examination was compared to those without PH in intra- or post- operative complications or outcomes. Measurements and Main Results: We collected clinical records of LDLT surgery for pediatric patients during the year of 2016 in our hospital. Results suggested that pediatric patients undergoing LDLT had a substantial number of PH with a prevalence of 16.1% in this study. No significant difference was identified between two groups of patients regarding intraoperative outcomes and postoperative complications and mortality. Conclusion: LDLT is a safe procedure in a selected group of BA patients with PH, however, further long-term clinical investigations and mechanical researches are needed.