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Background The intestine is the well-acknowledged important organ where the nutritional molecules are absorbed. Meanwhile, intestinal ailments, including intestinal mucosal atrophy, barrier dysfunction (leaky gut), inflammation bowel disease (ulcerative colitis and Crohn's disease), irritable bowel syndrome (IBS), dysbacteriosis, and cancers (sporadic and colitis-associated intestinal cancers), have always been the top-ranking diseases that we are confronting. However, although there are several reports on the intestinal modulatory effects for the food macromolecular components (polysaccharides and prebiotics), the effects of low-molecular-weight phytochemicals from foods, especially those from functional foods, on intestinal ailments have not been methodically understood. Scope and approach Various functional foods and their low-molecular-weight phytochemicals that help protect intestinal homeostasis have been demonstrated. The preliminary in vitro results are not included due to the uncertainty of their in vivo efficacy. This review compiles only in vivo bioactive reports and findings with solid pieces of evidence (both human and animal-based ones) to demonstrate the practical use of the food and its low-molecular-weight phytochemicals as complementary therapies or dietary supplements for intestinal health and their underlying mechanism of action. Key findings and conclusions Functional foods (both the whole food and extracts) and their low-molecular-weight phytochemicals can benefit intestinal health of both small and large intestines at different stages of intestinal ailments through promoting intestinal epithelial renewal and barrier function, restoring intestinal flora, inhibiting intestinal inflammation and tumor growth, and exerting intestinal-cancer preventive effects. Therefore, depending on the circumstances of the intestinal ailment, intake of certain functional foods or their low-molecular-weight phytochemicals can relieve the symptom of intestinal ailments and contribute to the maintenance of intestinal homeostasis at different levels.

Background Given the serious impact of the COVID-19 outbreak on the mental health of Chinese adolescents, this study aimed to examine the proportion of anxiety and its correlates among Chinese adolescents with depression during the pandemic. Methods This cross-sectional online survey was conducted from February 20th to February 27, 2020 in China. Symptoms of depression and anxiety were assessed by the 20-item Center for Epidemiological Studies-Depression (CES-D) and 7-item Generalized Anxiety Disorder (GAD-7), respectively. Results In this study, 3,498 adolescents with depression were identified. Of them, the proportion of anxiety was 45.1% (95% confidence interval [CI]=43.5%-46.8%). Multiple logistic regression analysis revealed that being concerned about graduation (OR=1.25, P=0.002, 95% CI=1.09-1.43), sleep duration 8hr/day (OR=1.21, P=0.02, 95% CI=1.03-1.42), and quantity of homework higher than before (OR=1.68, P

Atypical porcine pestivirus (APPV), a highly divergent pestivirus, has a wide geographical distribution around the world. APPV is known to cause type A-II congenital tremors in newborn piglets. The main objective of this study is to access APPV prevalence in the US swine herds utilizing a newly developed quantitative real-time RT-PCR assay. Retrospective analysis of 1,785 samples revealed a 19.0% prevalence in Midwest swine herds over a period of three years (2016-2018). Among all clinical and field samples that were APPV positive, 82 samples (24.19%) were also positive for one or more swine viral pathogens. Two APPV US strains identified in this study demonstrated significant sequence diversity (~12% in full genome) compared to the first reported APPV strain from the United States in 2014. Of the two strains identified in this study, USA/023005/2016 is closer to two strains identified in Germany, and USA/047310/2017 shares more similarities with two US strains including Minnesota-1 and ISDVDL2014016573. Partial NS5B sequences (9127-9836 nt of the polyprotein gene) obtained from 54 APPV-positive samples revealed considerable sequence diversity, ranging from 85.8% to 100% nucleotide identity, within the US strains in samples from different geographic regions. Analysis of all US samples indicates high prevalence of APPV in Minnesota (37.35%), followed by Illinois (32.86%), Iowa (30.60%) and Kansas (21.89%). APPV was detected in 15.48% of samples assayed from 2017, slightly higher than that in 2016 (13.08%), but much lower than 2018 (28.77%). Among the various sample types tested, oral fluid samples had the highest prevalence and lowest average Ct value suggesting their suitability as a reliable diagnostic specimen for APPV detection. Overall, sequence variation among APPV strains and prevalence of the pathogen within the United States provides a basis for understanding the genetic diversity and molecular epidemiology of APPV in the US swine herds.

To examine a predictive theoretical model of psychological distress based on the following variables reflected on family caregivers of patients with cancer: the unmet supportive care needs, subjective caregiving burden, social support, and the positive aspects of caregiving. A cross-sectional descriptive study was conducted on a sample of 484 dyads of patients and their family caregivers. The caregivers completed structured questionnaires designed to measure psychological distress, unmet supportive care needs, subjective caregiving burden, positive aspects of caregiving, and social support. Patients’ demographic variables and medical data were collected from a medical record review. We used a structural equation modeling to test the predictive theoretical model. Path analysis results partially supported the proposed model with satisfactory fit indices. Specifically, family caregivers with an increasing number of unmet needs or a heavier caregiving burden were more likely to have more severe psychological distress. Bootstrapping results supported that the caregiving burden and social support were significant mediators. Greater unmet supportive care needs predicted higher psychological distress through increasing caregiving burden. Stronger social support predicted lower psychological distress through decreasing caregiving burden. Positive aspects of caregiving predicted lower caregiving burden through the increasing perceived social support, which in turn eliminated psychological distress. Unmet supportive care needs could cause psychological distress through increasing caregiving burden. The positive aspects of caregiving reduced caregiving burden through increasing social support, which subsequently alleviated psychological distress. Interventions that aim to satisfy supportive care needs, to reduce caregiving burden, and to strengthen social support ties may boost the mental health of family caregivers.

Background and aims Glucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS). Methods and results A total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013). Conclusion After adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.

Abstract Measurement the viscoelastic properties is important for studying the developmental and pathological behavior of soft biological tissues. Magnetic resonance elastography (MRE) is a non-invasive method for in vivo measurement of tissue viscoelasticity. As a flexible method capable of testing small samples, indentation has been widely used for characterizing soft tissues. Using 2nd-order Prony series and dimensional analysis, we analyzed and compared the model parameters estimated from both indentation and MRE. Conversions of the model parameters estimated from the two methods were established. We found that the indention test is better at capturing the dynamic response of tissues at a frequency less than 10 Hz, while MRE is better for describing the frequency responses at a relatively higher range. The results provided helpful information for testing soft tissues using indentation and MRE. The models analyzed are also helpful for quantifying the frequency response of viscoelastic tissues. Graphic Abstract

To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia.Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group.Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD)Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.

Background Radiofrequency ablation (RFA) is being considered as the favorable treatment option for unresectable colorectal cancer liver metastases (CRLM) receiving chemotherapy, yet there still exist challenges for recurrence after RFA. The present study aims to establish an effective nomogram to predict intrahepatic progression-free survival (PFS) and select RFA candidates. Methods Patients with unresectable CRLM treated with chemotherapy followed by RFA between 2010 and 2016 were enrolled in this study. The nomogram to predict intrahepatic PFS was established based on multivariable Cox regression analysis. The predictive performance of the nomogram was assessed according to the C-index, calibration plots and Kaplan–Meier curve. Results Of a total of 158 patients, the earlier new intrahepatic metastases over local tumor progression were observed in 157 patients during the follow-up, and the mean intrahepatic PFS was 16.9 ± 1.4 months in the present cohort. The optimal cutoff value of tumor size after chemotherapy was identified as 16 mm by X-tile analysis. Based on multivariate analysis, independent prognostic factors for intrahepatic PFS included primary positive lymph nodes, multiple metastases, tumor size >16 mm, no primary lesion resection, mutant KRAS and PD response after chemotherapy. The nomogram was established to predict intrahepatic PFS based on all independent factors, which achieved favorable discrimination and calibration. Conclusion This study firstly established the nomogram to predict intrahepatic PFS for unresectable CRLM patients receiving chemotherapy followed by RFA. It can facilitate the selection of RFA candidates, and help both surgeons and patients choose individualized regimens in the treatment decision.

With the development of endoscopic therapy, argon plasma coagulation (APC) has been widely used by endoscopists. It has many advantages, such as simple to operate, low cost, and minimal invasiveness. Because of its capability of lesion ablation and hemostasis, APC has several indications in the gastrointestinal tract. One of them is esophageal varices. The aim of this review is to summarize the research on APC in this field to provide a reference for clinical practice.

The post-translational modification (PTM) serves as an important molecular switch mechanism to modulate diverse biological functions in response to specific cues. Though more commonly found in eukaryotic cells, many PTMs have been identified and characterized in bacteria over the past decade, highlighting the importance of PTMs in regulating bacterial physiology. Several bacterial PTM enzymes have been characterized to function as the toxin component of type II TA systems, which consist of a toxin that inhibits cell growth and an antitoxin that protects the cell from poisoning by the toxin. While TA systems can be classified into seven types based on nature of the antitoxin and its activity, type II TA systems are perhaps the most studied among the different TA types and widely distributed in eubacteria and archaea. The type II toxins possessing PTM activities typically modify various cellular targets mostly associated with protein translation and DNA replication. This review mainly focuses on the enzymatic activities, target specificities, antitoxin neutralizing mechanisms of the different families of PTM toxins. We also proposed that TA systems can be conceptually viewed as molecular switches where the ‘on’ and ‘off’ state of the system is tightly controlled by antitoxins and discussed the perspective on toxins having other physiologically roles apart from growth inhibition by acting on the nonessential cellular targets.

Objectives. To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics. Methods and Results. Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent. Conclusion. This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

Computational modeling of the brain is crucial for the study of traumatic brain injury. An anatomically accurate model with refined details could provide the most accurate computational results. However, computational models with fine mesh details could take prolonged computation time that impedes the clinical translation of the models. Therefore, a way to construct a model with low computational cost while maintaining a computational accuracy comparable with that of the high-fidelity model is desired. In this study, we constructed magnetic resonance (MR) image-based finite element (FE) models of a mouse brain for simulations of controlled cortical impact. The anatomical details were kept by mapping each image voxel to a corresponding FE mesh element. We constructed a super-resolution neural network that could produce computational results of a refined FE model with a mesh size of 70 μm from a coarse FE model with a mesh size of 280 μm. The peak signal-to-noise ratio of the reconstructed results was 33.26 dB, while the computational speed was increased by 50-fold. This proof-of-concept study showed that using machine learning techniques, MR image-based computational modeling could be applied and evaluated in a timely fashion. This paved ways for fast FE modeling and computation based on MR images. Results also support the potential clinical applications of MR image-based computational modeling of the human brain in a variety of scenarios such as brain impact and intervention.Graphical abstract MR image-based FE models with different mesh sizes were generated for CCI. The training and testing data sets were computed with 5 different impact locations and 3 different impact velocities. High-resolution strain maps were estimated using a SR neural network with greatly reduced computational cost.

In this study, the whole mitochondrial genomes (mitogenomes) from four species were sequenced. The complete mitochondrial genomes of Sinopodisma pieli, S. houshana, S. qinlingensis, and S. wulingshanensis are 15,857 bp, 15,818 bp, 15,843 bp, and 15,872 bp in size, respectively. The 13 protein-coding genes (PCGs) begin with typical ATN codons, except for COXI in S. qinlingensis, which begins with ACC. The highest A+T content in all the sequenced orthopteran mitogenomes is 76.8% (S. qinlingensis), followed by 76.5% (S. wulingshanensis), 76.4% (S. pieli) and 76.4% (S. houshana) (measured on the major strand). The long polythymine stretches (T-stretch) in the A+T-rich region of the four species are not adjacent to the trnI locus but are inside the stem-loop sequences on the major strand. Moreover, several repeated elements are found in the A+T-rich region of the four species. Phylogenetic analysis based on 53 mitochondrial genomes using Bayesian Inference (BI) and Maximum Likelihood (ML) revealed that Melanoplinae (Podismini) was a monophyletic group; however, the monophyly of Sinopodisma was not supported. These data will provide important information for a better understanding of the phylogenetic relationship of Melanoplinae.

Mechanical properties of brain tissue can provide vital information for understanding the mechanism of traumatic brain injury (TBI). As mouse models were commonly adopted for TBI studies, a method to produce injury to the brain and characterize the injured tissue is desired. In this paper, a complete workflow of TBI induction, sample preparation, and biomechanical characterization is presented for measurement of the injured brain tissue. A controlled cortical impact device was used to induce injury to the brain. By setting the angle, speed, and position of the impact, the level of brain injuries could be controlled. Viscoelastic properties of both injured and non-injured brain tissues were measured using a ramp-hold indentation test. Regions of interests (ROIs) were tested and compared to contralateral corresponding counterparts. Methods introduced in this paper could be easily extended to produce and test a variety of other injured soft biological tissues.

This study examines the association between the new drug approvals released by the US Food and Drug Administration (FDA) and subsequent market stock price reactions for listed pharmaceutical and bi...

The MRN can be used to distinguish thickened nerve roots peripheral neuropathies and nonthickened nerve roots peripheral neuropathies. We found the MRN of either the brachial plexus or the lumbosacral plexus has a high diagnostic accuracy for CIDP, and the combined examination does not significantly improve diagnostic accuracy., Study Design. We examined the chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients and non-CIDP patients who have similar symptoms and difficult to differential diagnosis with CIDP by magnetic resonance neurography to find the difference among them. Objective. To investigate the differential diagnostic value of magnetic resonance neurography (MRN) for CIDP and other peripheral neuropathies. Summary of Background Data. Thirty-two consecutive patients with CIDP and 22 non-CIDP patients with symptoms similar to CIDP and difficult to be discriminate were recruited and imaged as a control group between May 2017 and May 2019. Methods. In this prospective study, the brachial plexus and lumbosacral plexus of 32 CIDP patients and 22 non-CIDP patients were examined by MRN. The clinical features and the nerve roots cross-sectional area (CSA) of the brachial plexus and lumbosacral plexus were measured. Results. The CSA of nerve roots of CIDP, Charcot-Marie-Tooth disease type-1 and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes syndrome patients were all shown extensive by MRN. The sensitivity of MRN in diagnosing CIDP was 81.25% (26/32), the specificity was 68.18% (15/22), the positive predictive value was 78.79% (26/33), the negative predictive value was 71.43% (15/21), the accuracy was 75.93% (40/54), the misdiagnosis rate was 24.07% (13/54), and the kappa value was 0.498. Receiver operating characteristic analysis showed higher diagnostic accuracy for CIDP with the CSA of the lumbosacral plexus (area under the curve [AUC] = 0.762) and that of the brachial plexus (AUC = 0.762), and the combined of both examinations did not improve the diagnostic efficacy compared with either (AUC = 0.769). Conclusions. The nerve roots of CIDP, Charcot-Marie-Tooth disease type-1, and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes syndrome were difficult to distinguish by MRN. Atypical CIDP patients had less nerve root injury compared with typical CIDP patients. MRN of either the brachial plexus or the lumbosacral plexus had a high diagnostic accuracy for CIDP, and it is not necessary to perform both parts of the examination. Level of Evidence: 2

Recent studies have displayed that circular RNA plays a key regulatory role in tumorigenesis and development. However, evidence supporting the critical role of circular RNA in the prognosis of colorectal cancer (CRC) is still limited. This study was designed to screen and identify novel circular RNA biomarkers in CRC. The microarray analysis of circular RNA expression profile was performed in three matched CRC and normal tissues. Compared with normal mucosa, a total of 208 differentially expressed circular RNAs were found in CRC, of which 95 were upregulated and 113 were downregulated. Then, the top 10 circular RNAs with the most significant differential expression were selected for verification by quantitative polymerase chain reaction (qPCR) in the above samples. The results of qPCR basically coincided with the findings of microarray analysis. The hsa_circ_022382 expression was the most significant upregulation in CRC among the 10 circular RNAs validated by qPCR. Because hsa_circ_022382 is derived from the human FADS2 gene, we named it circFADS2. Next, the increased expression of circFADS2 was further confirmed by qPCR, and its correlation with clinicopathologic parameters was analyzed in 200 CRC tissues. Herein, the expression of circFADS2 was shown to increase in 187 cases and decrease in 13 cases of CRC, and the elevated circFADS2 expression was closely related to the size, differentiation, infiltration depth, lymphatic and distant metastasis, and tumor/node/metastasis (TNM) stage of CRC. The survival analyses by Kaplan–Meier method demonstrated that patients with higher circFADS2 expression levels had shorter overall survival time and vice versa. Cox regression and area under ROC curve analyses revealed that the circFADS2 expression may be a promised biomarker for prognosis of CRC patients and had better prediction value when combined with TNM stage. In conclusion, our study identifies circFADS2 as an oncogenic biomarker and a potential prognostic factor in CRC. Impact statement Colorectal cancer (CRC) is the third most common malignancy worldwide with the second highest mortality rate. Although multidisciplinary cooperative therapies are helpful for improving the survival of CRC patients, the prognosis remains poor. Therefore, it is imperative to seek new biomarkers for the development of individualized treatment for each CRC patient. Circular RNA, an endogenous transcript with specific covalent closed loop, exhibits higher stability, conservation and expression abundance than the corresponding linear component and thus may be utilized as a promised biomarker. Although the majority of studies have focused on circular RNA expression profiling in various types of cancers, evidence supporting their critical role in the diagnosis and prognosis of CRC is limited. This study aimed to screen and identify novel circular RNA biomarkers of CRC by chip analysis and qPCR verification, and to highlight their potential as targets for CRC prognosis, and therapy.

The toxin–antitoxin (TA) system is composed of a stable toxin and an unstable antitoxin that neutralizes the toxin. Being perhaps the most studied among the different TA types, type II TA systems are widely distributed and often exist in multiple copies within chromosomes of eubacteria and archaea. Exhibiting diverse molecular activities such as RNases, kinases, and acetyltransferases, type II TA systems have been confirmed to be involved in diverse biological processes including plasmid maintenance, phage inhibition, persistence, stress response, and biofilm formation. In this review, we summarize the current state of the research in the type II TA field, emphasizing the activation mechanism, structure–function relationship, and biological functions of type II TA systems.

The study recruited 168 patients diagnosed with major depressive disorder (MDD). The nine-item Patient Health Questionnaire (PHQ-9) and Perceived Deficits Questionnaire for Depression (PDQ-D) were lower and the Digit Symbol Substitution Test (DSST) was higher in the community volunteers than those in MDD patients. Depression-related scores (17-item Hamilton Depression Rating Scale [HAMD-17], Clinical Global Impressions-Severity of Illness Scale [CGI-S], and PHQ-9), functioning-related scores (Sheehan Disability Scale [SDS]), and Work Efficiency and Activity Damage-Specific Health Problems questionnaire work productivity loss were decreased, and the quality of life-related scores (European Quality of life-5 Dimensions [EQ-5D] utility score) were increased in the MDD patients. PDQ-D was decreased and DSST was increased with the increase of follow-up time. Linear regression indicated that cognitive symptoms (PDQ-D and DSST) improved more slowly than depressive symptoms (PHQ-9). At baseline, PDQ-D was related with functioning (SDS and work productivity loss). PDQ-D and DSST were related with EQ-5D utility score. In addition, at month 6, PDQ-D was related with functioning (SDS and work productivity loss) and EQ-5D utility score. Cognitive impairment might be a risk for MDD and MDD-related changes in the functioning and quality of life.

Background Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis. Methods High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter. Results In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-β signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS. Conclusions NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.

Ultrasound growth measurements are monitored to evaluate if a fetus is growing normally compared with a defined standard chart at a specified gestational age. Using data from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st project, we have modelled the longitudinal dependence of fetal head circumference, biparietal diameter, occipito-frontal diameter, abdominal circumference, and femur length using a two-stage approach. The first stage involved finding a suitable transformation of the raw fetal measurements (as the marginal distributions of ultrasound measurements were non-normal) to standardized deviations (Z-scores). In the second stage, a correlation model for a Gaussian process is fitted, yielding a correlation for any pair of observations made between 14 and 40 weeks. The correlation structure of the fetal Z-score can be used to assess whether the growth, for example, between successive measurements is satisfactory. The paper is accompanied by a Shiny application, see https://lxiao5.shinyapps.io/shinycalculator/ .

An increasing number of enzymes involved in serine biosynthesis have been identified and correlated with malignant evolution in various types of cancer. Here we showed that the overexpression of phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients.

BackgroundThis study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.MethodsThis double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.ResultsA total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.ConclusionsAfter 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Objectives We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. Background TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. Methods Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. Results A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. Conclusions Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined.A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials (In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment.This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.

Untargeted metabolomics technology was used to discover the metabolic pathways and biomarkers for revealing the potential biological mechanism of syringin on hepatitis B virus. Serum samples were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based comparative metabolomics coupled with pattern recognition methods and network pathway. In addition, the histopathology, HBV DNA detection of liver tissue, and biochemical indicators of liver function change were also explored for investigating the antiviral effect of syringin. In comparison to the model group, the metabolic profiles of the turbulence in transgenic mice tended to recover to the same as the control group after syringin therapy. A total of 33 potential biomarkers were determined to explore the metabolic disorders in the hepatitis B animal model, of which 25 were regulated by syringin, and 8 metabolic pathways, such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, were involved. Syringin markedly reduced the liver pathology change, inhibited HBV DNA replication, and improved liver function. Amino acid metabolism is a potential target for the treatment of hepatitis B. The hepatoprotective effect of syringin may contribute to ameliorating oxidative stress and preventing protein and DNA replication. Comparative metabolomics is a promising tool for discovering metabolic pathways and biomarkers of the hepatitis B animal model as targets to reveal the effects and mechanism of syringin, which benefits the development of natural products and advances the treatment of diseases.

The 2019 novel coronavirus disease (COVID-19) epidemic in China has presented substantial challenges to traditional forms of mental health service delivery. This review summarizes the expert consensus on the mental health treatment and services for severe psychiatric disorders during the COVID-19 outbreak developed by the Chinese Society of Psychiatry and other academic associations. The Expert Recommendations on Managing Patients with Mental Disorders during a Serious Infectious Disease Outbreak (COVID-19) outline the appropriate measures for psychiatric hospitals or psychiatric units in general hospitals, including the delivery of outpatient, inpatient, and community mental health services. The Expert Recommendations on Internet and Telehealth in Psychiatry during Major Public Health Crises (COVID-19) describe the assessment and treatment issues of internet-based mental health services during the COVID-19 outbreak. The expert consensus recommendations provide guidance for mental health professionals in managing psychiatric services during the COVID-19 outbreak in China. The experiences from China in addressing the challenges in the management of major psychiatric disorders may be useful and relevant to other countries who are combating the COVID-19 pandemic.

We aimed to assess the efficacy and safety of pulmonary vasodilators in patients after the Fontan procedure. The PubMed, EMBASE, and Cochrane Library databases were searched through November 2019 for studies comparing pulmonary vasodilators and controls in Fontan patients. The variables assessed included change in pulmonary resistance, heart function, exercise capacity, quality of life, mortality, and adverse events after drug administration. A random/fixed effects model was used to assess the mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CIs). Subgroup analysis was stratified by drug category. In total, 449 Fontan patients from 13 studies were included. Pooled estimates of the change in pulmonary arterial pressure (MD, - 1.07; 95% CI, - 2.75 to 0.60; p = 0.21), New York Heart Association class (MD, - 0.57; 95% CI, - 1.41 to 0.28; p = 0.19), peak oxygen consumption (MD, 1.46; 95% CI, 0.01 to 2.90; p = 0.05), Short Form 36 (MD, 1.39; 95% CI, - 0.62 to 3.39; p = 0.17), mortality (RR, 0.37; 95% CI, 0.08 to 1.65; p = 0.19), and any adverse event (RR, 0.94; 95% CI, 0.71 to 1.24; p = 0.64) were not significantly different between the drug and control groups. Likewise, most results of the subgroup analysis revealed no significant between-group differences. Pulmonary vasodilator therapy appears to be safe, but not beneficial, in the categories of pulmonary resistance, heart function, or quality of life in patients who have undergone a Fontan procedure. No significant evidence was found to confirm that most pulmonary vasodilators could improve exercise capacity in Fontan patients.

Follistatin-like protein 1 (FSTL1) plays a critical role in lung organogenesis, but is downregulated during lung cancer development and progression. The prognostic significance and functional consequences of FSTL1 downregulation in lung cancer are unclear. Here, reduced levels of FSTL1 were detected in various tumors compared with normal tissues and were associated with poor clinical outcome in patients with non–small cell lung cancer, particularly those with lung adenocarcinoma. FSTL1 expression negatively correlated with the metastatic potential of lung cancer cells. Antibody-based neutralization of extracellular FSTL1 increased cellular migration/invasion while addition of recombinant FSTL1 protein diminished the metastatic capacity of lung cancer cells in vitro and in vivo. Notably, treatment with FSTL1 effectively prevented the metastatic progression of lung cancer cells in an orthotopic animal model. Mechanistically, FSTL1 directly bound to the proform of secreted phosphoprotein 1 (SPP1)/osteopontin, restraining proteolytic activation of SPP1, which led to inactivation of integrin/CD44-associated signaling and rearrangement of the actin cytoskeleton. Combined low expression of FSTL1 and high expression of SPP1 predicted a poorer prognosis for patients with lung cancer. This study highlights the novel interaction between FSTL1 and SPP1 and new opportunities to effectively target SPP1-driven metastatic cancers characterized by FSTL1 downregulation. Significance: These findings describe the novel interaction between FSTL1 and SPP1 and its role in the metastatic progression of lung adenocarcinoma.

PURPOSE/BACKGROUND Lithium, a common medication used in bipolar disorder treatment, can exert an inhibitory effect on sodium and potassium channels and potentially cause cardiac electrical conduction disturbance and corrected QT (QTc) prolongation. This study aimed to examine whether lithium at therapeutic levels can change electrocardiographic parameters in different groups of patients with bipolar disorder and to identify the potential clinical risk factors. METHODS/PROCEDURES Standard 12-lead electrocardiogram data before and after lithium treatment in bipolar disorder patients after at least 2-week dropout of psychotropic medications were analyzed. FINDINGS/RESULTS A total of 39 patients with bipolar disorder receiving lithium treatment were enrolled. Nineteen patients (48.7%) exhibited increased from P wave beginning to QRS complex beginning intervals after lithium treatment (mean serum level, 0.653 ± 0.247 mmol/L). Twenty-four patients (61.5%) exhibited increased a combination of Q, R, and S waves complex durations and increased QTc intervals. Twenty-three patients (59.0%) exhibited increased corrected JT (JTc) intervals. The patient group with increased QTc or JTc intervals exhibited a higher mean systolic blood pressure than did the patient group without increased QTc (134.7 ± 19.2 mm Hg vs 115.7 ± 11.8 mm Hg, P = 0.020) or JTc intervals (134.4 ± 19.6 mm Hg vs 117.6 ± 13.3 mm Hg, P = 0.054), respectively. Biochemical and hemodynamic parameters were comparable between patients with and without increased a combination of Q, R, and S waves complex durations or from P wave beginning to QRS complex beginning intervals. IMPLICATIONS/CONCLUSIONS Elevated systolic blood pressure may be the risk factor for the ventricular conduction delay in bipolar disorder patients receiving lithium at therapeutic levels.

Objective. To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren’s syndrome (pSS). Methods. Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher’s exact analysis, Mann–Whitney U-test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value. Results. Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%). Conclusion. This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.

Background Bladder hyperthermic intracavitary chemotherapy (HIVEC) has good effectiveness for bladder cancer, but conventional HIVEC systems lack precision and convenient application. To test the safety of a new HIVEC device (BR-TRG-II-type) in pigs and to perform a preliminary clinical trial in patients with bladder cancer. Methods This device was tested on six pigs to optimize the temperature and time parameters. Then, 165 patients (HIVEC after transurethral resection (TUR), n = 128; or HIVEC, n = 37) treated between December 2006 and December 2016 were recruited. Mitomycin C (MMC) was the chemotherapeutic agent. A serum pharmacokinetic study was performed. The primary endpoints were tumor recurrence, disease-free survival (DFS), and cumulative incidence rate (CIR) during follow-up. The adverse effects were graded. Results The animal experiment showed that 45 °C for 1 h was optimal. HIVEC was successful, with the infusion tube temperature stably controlled at about 45 °C, and outlet tube temperature of about 43 °C in all patients, for three sessions. Serum MMC levels gradually increased during HIVEC and decreased thereafter. The mean DFS was 39 ± 3.21 months (ranging from 8 to 78 months), and the DFS rate was 89.1% during follow-up. No adverse events occurred. Conclusion The use of the BR-TRG-II-type HIVEC device is feasible for the treatment of bladder cancer. Future clinical trials in patients with different stages of bladder cancer will further confirm the clinical usefulness of this device. Trial registration chictr.org.cn: ChiCTR1900022099 (registered on Mar. 252,019). Retrospectively registered.

Background Inflammatory factors have been considered a significant factor contributing to the development and progression of glioma. However, the relationship between circulating inflammatory factors and glioma risk as well as their prognostic values in glioma patients is still inconclusive. Here, we performed a meta‐analysis to address this issue. Methods Relevant articles were identified through PubMed, EMBASE, the Cochrane Library, Web of Science, Wanfang database, and China National Knowledge Infrastructure (CNKI) from inception to February 2019. The weighted mean differences (WMDs) or standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to describe the predictive ability of the levels of circulating inflammatory factors on glioma risk. To evaluate the prognostic values of the circulating inflammatory factors in glioma, hazard ratios (HRs) with 95% CIs were used. Results Thirty‐one studies comprising 2587 patients were included. The overall analysis showed that increased circulating interleukin‐6 (IL‐6) [SMD 0.81 (95% CI: 0.21‐1.40; P = .008)], interleukin‐8 (IL‐8) [SMD 1.01 (95% CI: 0.17‐1.84; P = .018)], interleukin‐17 (IL‐17) [SMD 1.12 (95% CI: 0.26‐1.98; P = .011)], tumor necrosis factor‐α (TNF‐α) [SMD 1.80 (95% CI: 1.03‐2.56; P = .000)], transforming growth factor‐β (TGF‐β) [SMD 10.55 (95% CI: 5.59‐15.51; P = .000)], and C‐reactive protein (CRP) [SMD 0.95 (95% CI: 0.75‐1.15; P = .000)] levels were significantly associated with glioma risk. On the other hand, our results showed that circulating IL‐6 [HR 1.10 (95% CI: 1.05‐1.16; P = .000)] and CRP [HR 2.02 (95% CI: 1.52‐2.68; P = .000)] levels were highly correlated with a poor overall survival (OS) rate in glioma patients. Conclusion Our results indicate that increased circulating IL‐6, IL‐8, IL‐17, TNF‐α, TGF‐β, and CRP levels are significantly associated with increased glioma risk. Moreover, our meta‐analysis suggests that circulating IL‐6 and CRP may serve as powerful biomarkers for a poor prognosis in glioma patients., Inflammatory factors have been considered a significant factor contributing to the development and progression of glioma. Our meta‐analysis indicates that increased circulating IL‐6, IL‐8, IL‐17, TNF‐α, TGF‐β, and CRP levels are significantly associated with increased glioma risk. Moreover, it suggests that circulating IL‐6 and CRP may serve as powerful biomarkers for a poor prognosis in glioma patients.

We sought to assess the amount and distribution of force on the valve frame after transcatheter aortic valve replacement (TAVR) via patient-specific computer simulation. Patients successfully treated with the self-expanding Venus A-Valve and multislice computed tomography (MSCT) pre- and post-TAVR were retrospectively included. Patient-specific finite element models of the aortic root and prosthesis were constructed. The force (in Newton) on the valve frame was derived at every 3 mm from the inflow and at every 22.5° on each level. Twenty patients of whom 10 had bicuspid aortic valve (BAV) were analyzed. The total force on the frame was 74.9 N in median (interquartile range 24.0). The maximal force was observed at level 5 that corresponds with the nadir of the bioprosthetic leaflets and was 9.9 (7.1) N in all patients, 10.3 (6.6) N in BAV and 9.7 (9.2) N for patients with tricuspid aortic valve (TAV). The level of maximal force located higher from the native annulus in BAV and TAV patients (8.8 [4.8] vs. 1.8 [7.4] mm). The area of the valve frame at the level of maximal force decreased from 437.4 (239.7) mm2 at the annulus to 377.6 (114.3) mm2 in BAV, but increased from 397.5 (114.3) mm2 at the annulus to 406.7 (108.9) mm2 in TAV. The maximum force on the bioprosthetic valve frame is located at the plane of the nadir of the bioprosthetic leaflets. It remains to be elucidated whether this may be associated with bioprosthetic frame and leaflet integrity and/or function.

Type 2 diabetes mellitus (DM) patients are at a higher risk for developing lung cancer due to immune dysfunction and chronic inflammation. They also have increased morbidity and mortality related to influenza, and it is recommended that they receive an annual influenza vaccination. In this study, we evaluate whether influenza vaccination could reduce the incidence of lung cancer in DM patients. This cohort study included DM patients (≥55 years old) between 1 January 2002 and 31 December 2012 by using the Taiwan Health Insurance Database. Cox proportional hazard regression method was used to compare the relation between the influenza vaccination and lung cancer incidence after adjusting for potential confounders. Sub-group analyses were done according to vaccination status (unvaccinated, total number of vaccinations: 1, 2–3, ≥4) and evaluated the dose-dependent effects on lung cancer events. Among 22,252 eligible DM patients, 7860 (35.32%) received an influenza vaccination and 67.68% (14392) did not receive an influenza vaccination. Lung cancer incidence was significantly lower in the vaccinated group versus the unvaccinated group (adjusted HR 0.77, 95% CI 0.62–0.95, p &lt, 0.05). Significant protective effects were observed among male sex (adjusted HR 0.72, 95% CI 0.55–0.94, p &lt, 0.05) and 55–64 year (adjusted HR 0.61, 95% CI 0.40–0.94, p &lt, 0.05) and ≥75 year (adjusted HR 0.63, 95% CI 0.42–0.92, p &lt, 0.05) age groups, respectively. A dose-dependent protective effect was noted with a significant protective effect in those that received ≥4 vaccinations (adjusted HR 0.42, 95% CI 0.29–0.61, p &lt, 0.001). In sub-group analysis, elder patients with ≥65 years of age were significantly protected from ≥4 vaccinations (adjusted HR 0.37, 95% CI 0.23–0.62, p &lt, 0.001 in 65–74 years and adjusted HR 0.31, 95% CI 0.15–0.66, p = 0.002 in ≥75 years group, respectively). Male sex with ≥4 vaccinations had a significantly lower risk of lung cancer (adjusted HR 0.35, 95% CI 0.21–0.57, p &lt, 0.001). Patients with comorbid conditions that received ≥4 vaccinations were also protected, and was especially significant among those with CCI ≥ 3 (adjusted HR 0.38, 95% CI 0.18–0.80, p = 0.009) as compared to 1 and 2–3 vaccination groups, including those with hypertension (adjusted HR 0.35, 95% CI 0.22–0.57, p &lt, 0.001). This population-based cohort study demonstrated that annual influenza vaccination significantly reduced the lung cancer risk in DM patients and specifically demonstrates that a higher number of vaccinations is related with a more protective effect. Whether this is due to vaccine booster effects on anti-tumor immune regulation among DM patients still needs to be explored.

Turner syndrome is a clinical syndrome caused by autosomal abnormalities in women. It is often accompanied by congenital cardiovascular malformations commonly including a bicuspid aortic valve malformation and aortic coarctation, but the presence of multiple pulmonary venous abnormalities is extremely rare. We present a 27-year-old woman who was diagnosed with Turner syndrome. She was revealed an anomalous right upper pulmonary venous connection, left upper pulmonary vein obstruction, and varicose vein malformations of the left pulmonary veins by a series of examination. Cardiac catheterisation and selective pulmonary angiography can further confirm the diagnosis, morphological characteristics, haemodynamic significance and provide a reference for the next step of treatment.

Simple Summary The hypoxic inducible factor 1A (HIF1A) pathway has been known to play an important role in tumor progression in various cancers, including lower-grade (Grade II/III) gliomas (LGGs). An in silico analysis using 34 genes associated with the activity of the HIF1A pathway demonstrated that the BICD cargo adaptor 1 (BICD1) gene is a potential prognostic marker in LGGs. Moreover, BICD1 gene (BICD1) expression was positively correlated with CD274, GSK3B, HGF, and STAT3 expression in LGGs. Importantly, BICD1 downregulation was significantly associated with well-known favorable prognostic markers, such as a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR and younger patient age, in LGGs. Therefore, our findings present BICD1 as a new prognostic biomarker to more precisely predict the clinical outcomes of LGG patients in coordination with those well-known biomarkers. Abstract Although several biomarkers have been identified to predict the prognosis of lower-grade (Grade II/III) gliomas (LGGs), we still need to identify new markers to facilitate those well-known markers to obtain more accurate prognosis prediction in LGGs. Bioinformatics data from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Cancer Cell Line Encyclopedia (CCLE) datasets were used as the research materials. In total, 34 genes associated with the HIF1A pathway were analyzed using the hierarchical method to search for the most compatible gene. The BICD cargo adaptor 1 (BICD1) gene (BICD1) was shown to be significantly correlated with The hypoxic inducible factor 1A (HIF1A) expression, the World Health Organization (WHO) grade, and IDH1 mutation status. In addition, BICD1 downregulation was significantly correlated with a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR, and younger patient age in the enrolled LGG cohort. Moreover, BICD1 expression was significantly upregulated in wild-type IDH1 LGGs with EGFR mutations. Kaplan–Meier survival analysis revealed that BICD1 downregulation predicts a favorable overall survival (OS) in LGG patients, especially in those with IDH1 mutations. Intriguingly, we found a significant correlation between BICD1 downregulation and a decreased level of CD274, GSK3B, HGF, or STAT3 in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.

Background: Bipolar disorder (BD) is a severe psychiatric disorder that is often misdiagnosed and under-diagnosed in clinical settings. The 33-item Hypomania Checklist (HCL-33) is a newly developed self-administered scale for BD detection, while the 33-item Hypomania Checklist-external assessment (HCL-33-EA) is a version of the HCL-33 for external rating used by patient's carer (e.g., family member or friend). We aimed to compare the screening abilities between the HCL-33 and the HCL-33-EA, and evaluate the screening consistency between the two scales.Methods: The data were collected from 269 patients with diagnosed BD (n = 84) or major depressive disorder (MDD) (n = 185). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) between the HCL-33 and the HCL-33-EA for BD were compared against clinician diagnosis as the gold standard.Results: Using Youden's index, the optimal cut-off value of the HCL-33 is 20, while the corresponding figure for HCL-33-EA is 11. Using Youden's index, the HCL-33-EA showed a better performance than the HCL-33 (0.51 vs.0.41). The HCL-33-EA was more sensitive in correctly identifying BD patients from MDD patients than the HCL-33 (0.83 vs. 0.59), while the HCL-33 presented better specificity than the HCL-33-EA (0.82 vs. 0.68). There was significant screening consistency between the two scales (p < 0.001).Conclusions: Both scales have acceptable psychometric properties in detection BD from MDD. Use of the two scales should be considered based on the assessment purpose in clinical research or daily practice (i.e., prefer sensitivity or specificity). Noticeably, the current sample size is insufficient and future studies are recommended to further evaluate the scales.

Coronary artery fistula is an abnormal direct connection between the coronary artery and any of the four chambers of the heart or great vessels. A fistula from the left circumflex coronary artery to the coronary sinus is a relatively rare situation. We report a case of 12-month-old infant with coronary artery fistula from the left circumflex coronary artery to the coronary sinus that was identified incidentally. The N-terminal pro-brain natriuretic peptide level was elevated. Additionally, the proximal segment of the left circumflex coronary artery was dilated. On the basis of these findings, percutaneous closure of the fistula was performed with a vascular plug. This procedure achieved no residual flow and good hemodynamics were observed during follow-up.

Transcatheter aortic valve replacement (TAVR) is a mature technique in treating patients with severe aortic stenosis. However, permanent pacemaker implantation (PPMI) still remains a common complication after TAVR, especially in patients treated with self-expandable valves ([1][1]). Implantation

Background Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. Methods We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). Results Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. Conclusion Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. Significance: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non–small lung cancer and that blocking this interaction could be an effective cancer treatment.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially deadly manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the clinical characteristics and risk factors of DAH in SLE. A systematic review and meta-analysis of previous observational studies compared the clinical characteristics and risk factors between DAH-SLE and SLE patients without DAH. A total of 5 observational studies were included in this meta-analysis. Compared with the SLE patients without DAH, DAH-SLE patients had a significantly higher incidence of neuropsychiatric events (OR = 4.321, 95% CI (1.686–11.073), P = 0.002, I2 = 49.2%), nephritis (OR = 3.146, 95% CI (1.663–5.955,), P = 0.000, I2 = 0.0%), serositis (OR = 6.028, 95% CI (1.418–25.635), P = 0.015, I2 = 80.3%), dyspnea (OR = 31.241,95% CI (0.202–4833.203), P = 0.181, I2 = 94.6%), and a significantly lower level of C3 (SMD = − 1.358, 95% CI − 1.685, − 1.031), P = 0.000, I2 = 98.0%), C4 (SMD = − 1.251, 95% CI (− 1.648, − 0.855), P = 0.000, I2 = 87.7%), hemoglobin (SMD = − 2.074, 95% CI (− 2.433, − 1.715), P = 0.000, I2 = 94.2%), and a higher SLEDAI-2K score (SMD = 1.284, 95% CI (0.959, 1.608), P = 0.000, I2 = 98.2%). However, due to significant heterogeneity, some of these results should be interpreted cautiously. Nevertheless, when the above abnormal indicators are found, especially neuropsychiatric involvement and nephritis, besides the existed diagnostic criteria for DAH in SLE patients, a diagnosis for DAH should be considered and relevant treatment timely initiated. Further prospective multi-center SLE studies with a large cohort of patients and long-term follow-up are needed to clarify further or find out the specific clinical indexes for DAH in SLE patients.

Purpose Thermo-chemotherapy (TCT) is a new approach for the treatment of cancer that combines chemotherapy with thermotherapy. In the present study, we investigated the relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and TCT sensitivity in gastric cancer (GC) to further illuminate the molecular mechanism underlying the effect of TCT on GC. Methods A TCT cell model was constructed, and EIF5A2 was silenced or overexpressed by infection with a lentivirus expressing either EIF5A2 or EIF5A2 shRNA. Then, RT-qPCR, Western blotting, and immunohistochemistry assays were performed to evaluate the changes in the expression levels of EIF5A2, c-myc, vimentin, and E-cadherin. Cell proliferation and xenograft assays were conducted to evaluate the effect on cell proliferation. Finally, wound-healing and Transwell invasion assays were performed to evaluate the effects on migration and invasion. Results TCT reduced EIF5A2 expression at both the mRNA and protein levels. It also inhibited cell proliferation, migration, and invasion, downregulated the expression of c-myc and vimentin, and increased the expression of E-cadherin in both MKN28 and MKN45 cells. Silencing of EIF5A2 enhanced the above effects of TCT on MKN28 and MKN45 cells, while overexpression of EIF5A2 had the opposite effects. In addition, EIF5A2 overexpression weakened the inhibitory effect of TCT on tumor growth in vivo as well as the effects on c-myc, vimentin, and E-cadherin. Conclusion TCT inhibits GC cell proliferation and metastasis by suppressing EIF5A2 expression. Our results provide new insights into our understanding of the molecular mechanism underlying the effects of TCT in GC.

OBJECTIVE To analyze whether the bilirubin level is a protective factor in ulcerative colitis (UC) and the predictive value of the bilirubin level. PATIENTS AND METHODS We compared the bilirubin levels of 100 UC patients and 140 healthy controls as well as those of the subgroups of patients with different UC severities and then analyzed the correlation between the bilirubin level and UC and the correlations among the erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP) level, UC severity, and bilirubin level. The predictive value of the bilirubin level for UC was determined by constructing a receiver operating characteristic (ROC) curve. RESULTS The mean levels of the total bilirubin (TBIL) and indirect bilirubin (IBIL) in the UC were lower in comparison with the mean TBIL and IBIL levels in the control group, and the TBIL and IBIL levels were significantly higher in the mild activity subgroup than in the moderate and severe activity subgroups (P

AIM Inflammatory joint diseases (IJDs) are chronic arthritis, but frequently present with co-morbidities of other organs and systems, which is known as extra-articular manifestations (EAMs). It is still unclear which clinical characteristics or bio-markers can predict the development of EAMs. The aim of this study was to estimate the proportion of EAMs in southern Chinese patients with IJDs and to explore the risk factors. METHODS This was a retrospective cohort study of a total 1135 IJDs patients, including 788 rheumatoid arthritis (RA) patients, 307 ankylosing spondylitis (AS) patients and 40 psoriatic arthritis (PsA) patients. Demographic data, disease characteristics, laboratory blood tests, medical imaging, and the presence of EAMs were recorded. RESULTS We found 459 (40.44%) patients presented with EAMs: 30.84% had cardiovascular involvement, 7.67% had pulmonary involvement, 5.29% had osteoporosis/low bone mineral density, 2.29% had ocular, 0.79% had gastrointestinal and 0.26% had renal involvements. Multivariate logistic regression showed older age (odds ratio [OR] 1.06, P

Highlights • A multiplex real-time PCR assay was developed for PCV2 and PCV3 detection and differentiation. • Sensitivity was determined by standard curves with viral isolates and positive diagnostic samples. • Specificity was determined by testing common swine viruses. • The assay was validated on 336 swine diagnostic samples. • Limited data indicated that PCV3 has higher prevalence than PCV2 in the US., A multiplex quantitative real-time polymerase chain reaction (mqPCR) assay was developed and validated for the detection and differentiation of porcine circovirus type 3 (PCV3) and type 2 (PCV2) strains. The assay coverage was 97.9% (184/188) for PCV3 and 99.1% (1889/1907) for PCV2 sequences that were available from the current GenBank database. The PCR amplification efficiencies were 98–99% for plasmids, and 92–96% for diagnostic samples, with correlation coefficients all greater than 0.99. The limit of detection (LOD) determined as plasmid copies per reaction was 17 for PCV3 and 14 for PCV2. The assay specifically detected the targeted viruses without cross reacting to each other or to other common porcine viruses. Among 336 swine clinical samples collected in 2018, 101 (30.1%) were PCV3 positive, 56 (16.7%) were PCV2 positive and 18 (5.4%) were co-positives. Sixty selected PCV3 positives were confirmed by Sanger sequencing, and 53 of the 56 PCV2 positive samples were tested positive by another validated PCR assay.

Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and is characterized by mesangial cell proliferation and agglomeration of the mesangial matrix. Methods In this study, we aimed to explore the role of TNS3, PHLDB1, NTN4, and GNG2 3′untranslated region (3′UTR) polymorphisms with the risk of IgAN in a Chinese Han cohort. A logistic recession model was used to calculate the effects of candidate single nucleotide polymorphism (SNP) on IgAN risk after adjusting age and gender difference. In silico prediction was conducted to identify potential functions of SNPs. Results The analysis revealed a significant relationship between the homozygotic genotype for NTN4 rs1362970 A/A and higher risk of IgAN (p = 0.003). Statistically significant associations were found when the sample was stratified by gender and Lee's grade. As a result, NTN4 rs1362970 A/A and GNG2 rs3204008 G/G genotypes were associated with enhanced IgAN risk in males (p = 0.006, p = 0.023, respectively), and the association between the PHLDB1 rs7389 G/T genotype and higher IgAN risk was found in females (p = 0.008). In the Lee's grade III–V subgroup, the rs1369270 in NTN4 was significantly correlated with the risk of IgAN (p = 0.004). Bioinformatics prediction suggested that rs1362970 within NTN4 3′UTR was located in the potential target sequence of miR-483-5p. Conclusions Our research confirmed that NTN4, GNG2, and PHLDB1 gene polymorphisms were implicated in IgAN susceptibility in Chinese Han population. Further research should be conducted to investigate and validate the mechanism by which the above-mentioned polymorphisms affect IgAN.

Background The molecular mechanism underlying clear cell renal cell carcinoma (ccRCC) metastasis remains unclear. We therefore aimed to elucidate the role of IMPA2 in ccRCC metastatic progression. Methods Using the Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) staining, we investigated differences in IMPA2 mRNA and protein expression, as well as their clinical relevance, in ccRCC. To investigate the function of IMPA2 in ccRCC metastasis, we performed in vitro migration and in vivo lung colony-forming assays. We further explored the effect of microRNA (miR)-25 on IMPA2 expression by performing a luciferase reporter assay. Findings We show that ccRCC expresses relatively lower transcript levels of IMPA2 than normal kidney tissue. IMPA2 downregulation was greater in high-grade ccRCC than in low-grade ccRCC and was correlated with a poor prognosis in ccRCC patients. Importantly, we demonstrate that IMPA2 expression is inversely associated with the metastatic potential of ccRCC cells. We found that IMPA2 knockdown promotes, but overexpression suppresses, the cellular migration and lung colony-forming abilities of ccRCC cells. By using in silico and luciferase reporter assays, we found that IMPA2 expression is primarily influenced by miR-25 in ccRCC cells. Significantly, the inhibition of miR-25 function restored IMPA2 expression, thereby diminishing the metastatic potential of ccRCC cells. Interpretation We conclude that miR-25-mediated IMPA2 downregulation constitutes a novel signature for cancer metastasis and poor outcomes in ccRCC. We further postulate that the therapeutic targeting of miR-25 can be useful for preventing the metastatic progression of ccRCC associated with IMPA2 downregulation. Fund This study was supported by the Ministry of Science and Technology, Taiwan (MOST 107-2314-B-038-094, MOST 106-2314-B-038-069-MY3, MOST 105-2320-B-038-021-MY3 and MOST 107-2320-B-038-056).

The authors sought to better understand the stent geometry of the Lotus valve after transcatheter aortic valve replacement (TAVR) and its potential implications for valve size selection.The authors hypothesized that the greatest interference between the frame and aortic valvar complex occurs across the aortic valve leaflets.The authors retrospectively analyzed the multidetector computed tomography (MDCT) scans of 32 consecutive patients undergoing Lotus valve (Boston Scientific, Natick, Massachusetts) implantation. The prosthesis cross section was analyzed at 3-mm increments along its length. The plane where the frame had the smallest area was defined as the waist. The corresponding plane of the waist on pre-procedural MDCT was identified by surrounding structures such as calcium deposits, commissural fusion, and commissural gaps, and was referred to as the supra-annulus. The spline of the supra-annulus was circumscribed with reference to the post-implant stent geometry at the waist.The waist was 5.8 ± 1.7 mm higher than the native annulus on post-procedural MDCT. The waist had a nearly 2-fold larger compression rate than the stent at the native annulus level (36.3 ± 10.4% vs. 18.9 ± 9.6%; p 0.01), irrespective of valve morphologies. The supra-annulus was 5.9 ± 1.6 mm higher than the annulus on pre-procedural MDCT. Patients had an approximately 17% decrease in area from the annulus to the supra-annulus (18.3 ± 4.4% for bicuspid morphology and 16.0 ± 3.5% for tricuspid morphology).Major interference between the implanted prosthesis and anatomy occurred at a level above the annulus. The decrease in area from the annulus to supra-annulus may explain the feasibility of implanting a smaller valve than that suggested by traditional annular measurements.