Publications by authors named "Wen Xie"

540 Publications

Serum markers for predicting advanced fibrosis in patients with chronic hepatitis B and nonalcoholic fatty liver disease.

Medicine (Baltimore) 2021 May;100(18):e25327

Center of Liver Diseases.

Abstract: To compare the diagnostic utility of serum markers in nonalcoholic fatty liver disease (NAFLD) patients with chronic hepatitis B (CHB).This study enrolled 118 consecutive biopsy-proven NAFLD patients with or without CHB. Fibrosis scores of each marker were compared against histological fibrosis staging. Receiver operating characteristic curve (ROC) analysis helped assess the accuracy of each marker.In patients with both diseases, 12.96% (7/54) had advanced fibrosis on biopsy and aspartate aminotransferase (AST) to platelet ratio index was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC (95% confidence interval) for AST to platelet ratio index (APRI) were 0%, 93.62%, 0%, 86.27%, and 0.676 (0.524-0.828), respectively. The markers ranked as follows from highest to lowest with respect to their accuracy: APRI; BARD; fibrosis-4; and AST to ALT ratio. In patients without CHB, fibrosis-4 was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, PPV, NPV, and area under the ROC (95% confidence interval) for fibrosis-4 were 77.78%, 85.45%, 46.67%, 95.92%, and 0.862 (0.745-0.978), respectively.Serum markers are less reliable in predicting advanced fibrosis in NAFLD patients with CHB; APRI is the most accurate predictor of the absence of advanced fibrosis.
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http://dx.doi.org/10.1097/MD.0000000000025327DOI Listing
May 2021

Early and consecutive RT-PCR tests with both oropharyngeal swabs and sputum could improve testing yield for patients with COVID-19: An Observation Cohort Study in China.

Int J Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China. Electronic address:

Objective: The real-time polymerase chain reaction (RT-PCR) test is recommended for diagnosis of COVID-19 and provides a powerful tool to identify new infections and contact tracing. In fact, as COVID-19 prevalence decreases, this remains the main preventive measure to avoid rebound. However, inconsistent results due to biological sample variability in collection timing post infection and sampling procedures, misleads our application in clinic.

Methods: We applied Kaplan-Meier method and multivariate Logistic regression on the RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the negative percentages among patients who had tested twice or more and compared the proportions by oropharyngeal swab, sputum and combined double testing, respectively.

Main Results: The proportion of negative conversion was 6.7% at the 4 day, 16.4% at the 7 day, 41.0% at two weeks and 61.0% at three-weeks post-admission. We also found 34.1% and 60.3% with at least one negative RT-PCR result at the 7 days and 14 days after symptom onset, respectively. The negative proportion in sputum was higher than that in oropharyngeal swab in the early stage but lowered after symptoms.

Conclusion: In the absence of effective treatments or vaccines, efficient testing strategies are critical to control COVID-19 epidemic. According to this study, early, consecutive and combined double testing will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases, and minimize misdiagnosis and ineffective isolation of infected patients.
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http://dx.doi.org/10.1016/j.ijid.2021.04.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079261PMC
April 2021

WWP2 and PPP1R3A are abnormally regulated in arrhythmia-induced cardiac damage.

3 Biotech 2021 Apr 22;11(4):185. Epub 2021 Mar 22.

Department of Cardiology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072 Sichuan China.

The present work aimed to identify the roles of WWP2 (an E3 ubiquitin-protein ligase) and protein phosphatase 1 regulatory subunit 3A (PPP1R3A) in different pathological stages of cardiac arrhythmia development. Leptin-deficient mice (C57BLKS-Lepr/Lepr) were used for the development of initial and severe stages of cardiac arrhythmia. Histology, ECG, immunohistochemistry and Western blotting were used to analyse cardiac arrhythmia, WWP2 and PPP1R3A expression. Histopathological studies of 4-month-old mice showed cardiac degeneration, cellular lesions, and swollen tissue structure with loss of tissue elasticity, indicative of the initial condition of cardiac arrhythmia. The leptin-deficient 7-month-old mice showed cardiac tissue hardening with increased secretion of extracellular matrix. The development of initial- and severe-cardiac arrhythmia was further evident with electrocardiogram studies, which showed more PP interval variations as the disease progressed. At the molecular level, WWP2 showed marginal upregulation in the initial stages of arrhythmia and was predominantly expressed within nuclei. WWP2 was overexpressed 6.6-fold in the severe stage of cardiac arrhythmia and was spread throughout the tissue layer. Interestingly, PPP1R3A was significantly overexpressed in initial cardiac arrhythmia conditions, but was downregulated and restricted to more nuclear expression in advanced cardiac arrhythmia. Silencing of PPP1R3A, enhances the expression of WWP2 to 5.3-fold in initial stages, but remarkable variation not observed in advanced cardiac arrhythmia conditions. Our results suggest that PPP1R3A had a control over WWP2 in the initial stages of cardiac arrhythmia. In particular, PPP1R3A overexpression implies its potential protective effect in initial cardiac arrhythmia stages.
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http://dx.doi.org/10.1007/s13205-021-02719-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984132PMC
April 2021

Reactivation of SARS-CoV-2 infection following recovery from COVID-19.

J Infect Public Health 2021 Feb 8;14(5):620-627. Epub 2021 Feb 8.

Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun East Street, Chaoyang District, Beijing 100015, PR China. Electronic address:

Introduction: Many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA after recovering from the coronavirus disease (COVID-19), but the incidence of reactivation is unknown. We, therefore, estimated the incidence of reactivation among individuals who had recovered from COVID-19 and determined its predictors.

Methods: In this retrospective cohort study, patients with COVID-19 were followed up for at least 14 days after two consecutive negative SARS-CoV-2 polymerase chain reaction test results obtained ≥24 h apart, and the frequency of SARS-CoV-2 reactivation was assessed.

Results: Of the 109 patients, 29 (27%) experienced reactivation, and seven (24%) of these were symptomatic. The mean period for the real-time PCR tests for SARS-CoV-2 from negative to positive results was 17 days. Compared with patients without reactivation, those with reactivation were significantly younger and more likely to have a lymphocyte count of <1500/μL (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.12-0.94) and two or fewer symptoms (OR: 0.20, 95% CI: 0.07-0.55) during the initial episode.

Conclusion: Risk-stratified surveillance should be conducted among patients who have recovered from COVID-19.
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http://dx.doi.org/10.1016/j.jiph.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869688PMC
February 2021

Intestinal Sulfation is Essential to Protect Against Colitis and Colonic Carcinogenesis.

Gastroenterology 2021 Apr 2. Epub 2021 Apr 2.

Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania;; Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Background & Aims: Sulfation is a conjugation reaction essential for numerous biochemical and cellular functions in mammals. The 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the key enzyme to generate PAPS, which is the universal sulfonate donor for all sulfation reactions. The goal of this study is to determine whether and how PAPSS2 plays a role in colitis and colonic carcinogenesis.

Methods: Tissue arrays of human colon cancer specimens, gene expression data, and clinical features of cancer patients were analyzed. Intestinal-specific Papss2 knockout mice (Papss2) were created and subjected to dextran sodium sulfate (DSS)-induced colitis, and colonic carcinogenesis induced by combined treatment of azoxymethane (AOM) and DSS, or AOM alone.

Results: The expression of PAPSS2 is decreased in the colon cancers of mice and humans. The lower expression of PAPSS2 in colon cancer patients is correlated with worse survival. Papss2 mice showed heightened sensitivity to colitis and colon cancer by damaging the intestinal mucosal barrier, increasing intestinal permeability and bacteria infiltration, and worsening the intestinal tumor microenvironment. Mechanistically, the Papss2 mice exhibited reduced intestinal sulfomucin content. Metabolomic analyses revealed the accumulation of bile acids including the farnesoid X receptor (FXR) antagonist bile acid tauro-β-muricholic acid (T-β-MCA), and deficiency in the formation of bile acid-sulfates in the colon of Papss2 mice.

Conclusions: We have uncovered an important role of PAPSS2-mediated sulfation in colitis and colonic carcinogenesis. Intestinal sulfation may represent a potential diagnostic marker, and PAPSS2 may serve as a potential therapeutic target for inflammatory bowel disease and colon cancer.
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http://dx.doi.org/10.1053/j.gastro.2021.03.048DOI Listing
April 2021

Genome-Wide Identification and Analysis of Chitinase-Like Gene Family in (Hemiptera: Aleyrodidae).

Insects 2021 Mar 17;12(3). Epub 2021 Mar 17.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Chitinases are of great importance in chitin degradation and remodeling in insects. However, the genome-wide distribution of chitinase-like gene family in , a destructive pest worldwide, is still elusive. With the help of bioinformatics, we annotated 14 genes that encode putative chitinase-like proteins, including ten chitinases (Cht), three imaginal disk growth factors (), and one endo-β-N-acetylglucosaminidase () in the genome of the whitefly, . These genes were phylogenetically grouped into eight clades, among which 13 genes were classified in the glycoside hydrolase family 18 groups and one in the group. Afterwards, developmental expression analysis suggested that , and were highly expressed in nymphal stages and exhibit similar expression patterns, implying their underlying role in nymph ecdysis. Notably, nymphs exhibited a lower rate of survival when challenged by dsRNA targeting these three genes via a nanomaterial-promoted RNAi method. In addition, silencing of significantly resulted in a longer duration of development compared to control nymphs. These results indicate a key role of , and in nymph molting. Our research depicts the differences of chitinase-like family genes in structure and function and identified potential targets for RNAi-based whitefly management.
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http://dx.doi.org/10.3390/insects12030254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002649PMC
March 2021

A machine learning-based pulmonary venous obstruction prediction model using clinical data and CT image.

Int J Comput Assist Radiol Surg 2021 Apr 31;16(4):609-617. Epub 2021 Mar 31.

Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Dongchuan Rd 96, Guangzhou, 510080, China.

Purpose: In this study, we try to consider the most common type of total anomalous pulmonary venous connection and established a machine learning-based prediction model for postoperative pulmonary venous obstruction by using clinical data and CT images jointly.

Method: Patients diagnosed with supracardiac TPAVC from January 1, 2009, to December 31, 2018, in Guangdong Province People's Hospital were enrolled. Logistic regression were applied for clinical data features selection, while a convolutional neural network was used to extract CT images features. The prediction model was established by integrating the above two kinds of features for PVO prediction. And the proposed methods were evaluated using fourfold cross-validation.

Result: Finally, 131 patients were enrolled in our study. Results show that compared with traditional approaches, the machine learning-based joint method using clinical data and CT image achieved the highest average AUC score of 0.943. In addition, the joint method also achieved a higher sensitivity of 0.828 and a higher positive prediction value of 0.864.

Conclusion: Using clinical data and CT images jointly can improve the performance significantly compared with other methods that using only clinical data or CT images. The proposed machine learning-based joint method demonstrates the practicability of fully using multi-modality clinical data.
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http://dx.doi.org/10.1007/s11548-021-02335-yDOI Listing
April 2021

The relationship between clinical characteristics and magnetic resonance imaging results of Ménière disease: a prospective study.

Sci Rep 2021 Mar 30;11(1):7212. Epub 2021 Mar 30.

Department of Otolaryngology, Head and Neck Surgery & Audiology and Neurotology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Ménière disease (MD) is an idiopathic inner ear disorder, and endolymphatic hydrops (EH) being considered to be its pathological basis. Currently, there is no gold standard for diagnosing MD. Previous study has reported visualized EH using MRI by intratympanic gadolinium-based contrast media (GBCM) administration (IT-Gd) in patients with MD, and this technique was gradually established for MD diagnosis. However, few studies reported their diagnostic sensitivity and specificity in clinical application. This prospective study aimed at investigating the clinical characteristics and magnetic resonance imaging (MRI) results of patients with MD, and analyzing the relationship between clinical results and MRI findings in MD patients. Our study shows that the diagnostic sensitivity and specificity of MRI were 79.2% and 80.7% respectively. Moreover, there was no significant correlation between hearing levels and cochlear grading scores, nor vestibular grading scores. The duration of disease was not significantly associated with cochlear or vestibular grading scores. These findings suggest that IT-Gd MRI offers reliable radiological diagnostic criteria for MD.
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http://dx.doi.org/10.1038/s41598-021-86589-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010013PMC
March 2021

Whitefly hijacks a plant detoxification gene that neutralizes plant toxins.

Cell 2021 Apr 25;184(7):1693-1705.e17. Epub 2021 Mar 25.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Plants protect themselves with a vast array of toxic secondary metabolites, yet most plants serve as food for insects. The evolutionary processes that allow herbivorous insects to resist plant defenses remain largely unknown. The whitefly Bemisia tabaci is a cosmopolitan, highly polyphagous agricultural pest that vectors several serious plant pathogenic viruses and is an excellent model to probe the molecular mechanisms involved in overcoming plant defenses. Here, we show that, through an exceptional horizontal gene transfer event, the whitefly has acquired the plant-derived phenolic glucoside malonyltransferase gene BtPMaT1. This gene enables whiteflies to neutralize phenolic glucosides. This was confirmed by genetically transforming tomato plants to produce small interfering RNAs that silence BtPMaT1, thus impairing the whiteflies' detoxification ability. These findings reveal an evolutionary scenario whereby herbivores harness the genetic toolkit of their host plants to develop resistance to plant defenses and how this can be exploited for crop protection.
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http://dx.doi.org/10.1016/j.cell.2021.02.014DOI Listing
April 2021

Crucial roles of different RNA-binding hnRNP proteins in Stem Cells.

Int J Biol Sci 2021 8;17(3):807-817. Epub 2021 Feb 8.

Cancer Research Institute, Department of Neurosurgery, School of Basic Medical Science, Xiangya Hospital, Central South University, Changsha 410008, China.

The self-renewal, pluripotency and differentiation of stem cells are regulated by various genetic and epigenetic factors. As a kind of RNA binding protein (RBP), the heterogeneous nuclear ribonucleoproteins (hnRNPs) can act as "RNA scaffold" and recruit mRNA, lncRNA, microRNA and circRNA to affect mRNA splicing and processing, regulate gene transcription and post-transcriptional translation, change genome structure, and ultimately play crucial roles in the biological processes of cells. Recent researches have demonstrated that hnRNPs are irreplaceable for self-renewal and differentiation of stem cells. hnRNPs function in stem cells by multiple mechanisms, which include regulating mRNA stability, inducing alternative splicing of mRNA, epigenetically regulate gene expression, and maintaining telomerase activity and telomere length. The functions and the underlying mechanisms of hnRNPs in stem cells deserve further investigation.
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http://dx.doi.org/10.7150/ijbs.55120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975692PMC
February 2021

Activation and blockade of dorsal hippocampal serotonin4 receptors produce antidepressant effects in the hemiparkinsonian rats.

Brain Res 2021 Mar 15:147426. Epub 2021 Mar 15.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China; The Key Laboratory of Environment and Disease-Related Genes, Ministry of Education, Xi'an 710061, China. Electronic address:

Depression is a common non-motor symptom in Parkinson's disease (PD). Although serotonin4 (5-HT) receptors and the dorsal hippocampus (dHIP) are regarded to be involved in the depression, the mechanism underlying the effects of 5-HT receptors in the dHIP on PD-related depression should be further investigated. In the present study, unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB) increased the expressions of 5-HT receptors and its co-localization with glutamate neurons in the CA1, CA3 and dentate gyrus. Additionally, MFB lesions induced depressive-like behaviors in the sucrose preference and forced swimming tests. The activation or blockade of dHIP 5-HT receptors produced antidepressant effects in the MFB lesioned rats but not in control rats. Neurochemical results showed no changes of monoamines levels in the striatum, medial prefrontal cortex (mPFC), lateral habenula (LHb), and ventral hippocampus (vHIP) in control rats after intra-dHIP injection of 5-HT receptors agonist BIMU8 (26 μg/rat), antagonist GR 113808 (16 μg/rat) or GR 113808/BIMU8 (26 μg/16 μg/rat). But in the lesioned rats, BIMU8, GR113808 or GR 113808/BIMU8 injection increased dopamine levels in the striatum, mPFC, LHb, and vHIP and increased 5-HT levels in the LHb. Intra-dHIP injection of GR 113808 or GR 113808/BIMU8 also increased the noradrenaline levels in the mPFC and LHb. All these results suggest that activation or blockade dHIP 5-HT receptors produce antidepressant effects in the hemiparkinsonian rats, which may be related to the upregulation of 5-HT receptors in the dHIP and the changes of monoamines in the limbic and limbic-related brain regions.
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http://dx.doi.org/10.1016/j.brainres.2021.147426DOI Listing
March 2021

Yindan Jiedu Granules, a Traditional Chinese Medicinal Formulation, as a Potential Treatment for Coronavirus Disease 2019.

Front Pharmacol 2020 5;11:634266. Epub 2021 Feb 5.

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group ( = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group ( = 0.0180 and = 0.0028, respectively). YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.
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http://dx.doi.org/10.3389/fphar.2020.634266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957926PMC
February 2021

Two Deoxythymidine Triphosphate Synthesis-Related Genes Regulate Obligate Symbiont Density and Reproduction in the Whitefly MED.

Front Physiol 2020 24;11:574749. Epub 2021 Feb 24.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

Deoxythymidine triphosphate (dTTP) is essential for DNA synthesis and cellular growth in all organisms. Here, genetic capacity analysis of the pyrimidine pathway in insects and their symbionts revealed that dTTP is a kind of metabolic input in several host insect/obligate symbiont symbiosis systems, including MED/ (hereafter ). As such, the roles of dTTP on both sides of the symbiosis system were investigated in MED/. Dietary RNA interference (RNAi) showed that suppressing dTTP production significantly reduced the density of , significantly repressed the expression levels of horizontally transferred essential amino acid (EAA) synthesis-related genes, and significantly decreased the reproduction of MED adults as well as the hatchability of their offspring. Our results revealed the regulatory role of dTTP in MED/ and showed that dTTP synthesis-related genes could be potential targets for controlling as well as other sucking pests.
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http://dx.doi.org/10.3389/fphys.2020.574749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943623PMC
February 2021

Causes of Renal Allograft Injury in Recipients With Normal Donor-derived Cell-free DNA.

Transplant Direct 2021 Apr 5;7(4):e679. Epub 2021 Mar 5.

Division of Transplant Surgery, Department of Surgery, University of Maryland Medical Center, Baltimore, MD.

Background: Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for the early detection of organ transplant rejection and other causes of graft injury. For nonrejection renal injuries, there is little information about the performance characteristics of this biomarker. We highlight some of the possible causes of kidney injury that may arise in patients with normal dd-cfDNA levels.

Methods: We performed a retrospective analysis of solitary renal transplant cases between January 2017 and November 2019. Those who had an abnormal laboratory or pathological finding within 1 mo of a normal dd-cfDNA test were selected. Subgroups were stratified for those who had normal or abnormal/rising serum creatinine, and differences between the groups were analyzed.

Results: Of 414 individuals who received a kidney transplant, 24 (7.5%) had a total of 41 normal dd-cfDNA values and 51 abnormal laboratory tests or histologic findings. The most common graft-injuring event was BK virus viremia (24 of 51). Other abnormal findings included urinary traction infections (n = 4), CMV viremia (n = 4), and biopsies demonstrating antibody-mediated rejection (AMR) (n = 2), T cell-mediated rejection (n = 1), focal segmental glomerulosclerosis (n = 2), nondonor-specific antibody chronic AMR (n = 1), and interstitial fibrosis and tubular atrophy (n = 7). Subgroup analysis of those with normal dd-cfDNA and normal/stable versus abnormal/rising creatinine showed that BK virus viremia was the most common abnormal finding in both groups at 53% and 38% respectively. On biopsy, 1 case of acute T cell-mediated rejection (1B and 2B) was seen with normal/stable creatinine, whereas 1 of nonspecific C4d focally positive and 1 of nondonor-specific antibody AMR were seen with abnormal/rising creatinine.

Conclusions: Low levels of serum dd-cfDNA do not preclude detection of active graft-injuring events and that subclinical injuries may be developing. Context is important in the interpretation of dd-cfDNA, so renal biopsy remains a part of the diagnostic pathway for allograft dysfunction and maintenance of allograft health.
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http://dx.doi.org/10.1097/TXD.0000000000001135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935401PMC
April 2021

Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states.

Nat Neurosci 2021 04 8;24(4):542-553. Epub 2021 Mar 8.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.

In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (PO) to primary somatosensory cortex glutamatergic neurons (S1) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PF) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACC) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that PO and PF populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits PO→S1 and PF→ACC subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.
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http://dx.doi.org/10.1038/s41593-021-00811-xDOI Listing
April 2021

is required in part for the anti-obesity effect of constitutive androstane receptor (CAR).

Acta Pharm Sin B 2021 Feb 3;11(2):434-441. Epub 2020 Sep 3.

Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Crosstalk between xenobiotic metabolism and energy metabolism in the liver has provided a potential opportunity to target xenobiotic receptors to treat metabolic diseases. Activation of constitutive androstane receptor (CAR), a xenobiotic-sensing nuclear receptor, has been shown to inhibit obesity, suppress hepatic gluconeogenesis, and ameliorate hyperglycemia in rodent models of obesity and type 2 diabetes. However, the underlying molecular mechanism remains to be defined. The growth arrest and DNA damage-inducible gene 45b (), a well-known anti-apoptotic factor, has been shown to be an inducible coactivator of CAR in promoting rapid liver growth. It is unknown whether the effect of CAR on energy metabolism depends on GADD45B. In the present study and by using a high fat diet (HFD)-induced obesity model, we show that reduced body weight gain and improved insulin sensitivity by the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) were markedly blunted in knockout mice. Mechanistically, the TCPOBOP-responsive inhibition of hepatic lipogenesis, gluconeogenesis, and adipose inflammation observed in wild type mice were largely abolished in knockout mice. We conclude that is required in part for the metabolic benefits of CAR activation.
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http://dx.doi.org/10.1016/j.apsb.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893119PMC
February 2021

Targeting Xenobiotic Nuclear Receptors PXR and CAR to Prevent Cobicistat Hepatotoxicity.

Toxicol Sci 2021 04;181(1):58-67

Center for Pharmacogenetics, Department of Pharmaceutical Sciences.

Liver-related diseases including drug-induced liver injury are becoming increasingly prominent in AIDS patients. Cobicistat (COBI) is the backbone of multiple regimens for antiretroviral therapy. The current work investigated the mechanisms of adverse drug-drug interactions associated with COBI that lead to liver damage. For individuals co-infected with HIV and tuberculosis (TB), the World Health Organization recommends the initiation of TB treatment followed by antiretroviral therapy. Rifampicin (RIF), a first line anti-TB drug, is a human specific activator of pregnane X receptor (PXR). Using PXR-humanized mice, we found that RIF-mediated PXR activation potentiates COBI hepatotoxicity. In contrast, rifabutin, a PXR-neutral analog of RIF, has no impact on COBI hepatotoxicity. Because of the crosstalk between PXR and the constitutive androstane receptor (CAR), the role of CAR in COBI hepatotoxicity was also investigated. Similar to PXR, ligand-dependent activation of CAR also potentiates COBI hepatotoxicity. Our further studies illustrated that PXR and CAR modulate COBI hepatotoxicity through the CYP3A4-dependent pathways. In summary, the current work determined PXR and CAR as key modulators of COBI hepatotoxicity. Given the fact that many prescription drugs and herbal supplements can activate PXR and CAR, these two receptors should be considered as targets to prevent COBI hepatotoxicity in the clinic.
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http://dx.doi.org/10.1093/toxsci/kfab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081023PMC
April 2021

Annual analysis of field-evolved insecticide resistance in Bemisia tabaci across China.

Pest Manag Sci 2021 Feb 24. Epub 2021 Feb 24.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

Background: Over recent decades, many efficacious insecticides have been applied for control of Bemisia tabaci, one of the most notorious insect pests worldwide. Field-evolved insecticide resistance in B. tabaci has developed globally, but remains poorly understood in China.

Results: In this study, a total of 30 field samples of the whitefly Bemisia tabaci from eight provinces of China were collected in 2015 to 2018. Twenty-four of the populations were identified as Mediterranean, 'Q' type (MED), three were Middle East-Asia Minor 1, 'B' type (MEAM1), and three were mixtures of MED/ MEAM1. After identifying whether they belong to MED or MEAM1, the selected individuals were used in bioassays assessing insecticide resistance to abamectin, thiamethoxam, spirotetramat, cyantraniliprole, and pyriproxyfen. Our results showed that all populations in the eight regions had little or no resistance to abamectin; abamectin resistance was highest in the Hunan (Changsha) and Hubei (Wuhan) regions and was lowest in the island region of Hainan (Sanya). The resistance of B. tabaci to spirotetramat, cyantraniliprole, and pyriproxyfen increased each year. The resistance to thiamethoxam remained low because of the high LC value for the laboratory strain.

Conclusion: These findings suggest that a rotation system using efficacious B. tabaci insecticides with differing mode of actions ought to be implemented for sustainable control to reduce the potential of resistance development. This study provides important data to support the integrated pest management and insecticide resistance management of B. tabaci in China.
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http://dx.doi.org/10.1002/ps.6338DOI Listing
February 2021

The xenobiotic receptors PXR and CAR in liver physiology, an update.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 15;1867(6):166101. Epub 2021 Feb 15.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address:

Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two nuclear receptors that are well-known for their roles in xenobiotic detoxification by regulating the expression of drug-metabolizing enzymes and transporters. In addition to metabolizing drugs and other xenobiotics, the same enzymes and transporters are also responsible for the production and elimination of numerous endogenous chemicals, or endobiotics. Moreover, both PXR and CAR are highly expressed in the liver. As such, it is conceivable that PXR and CAR have major potentials to affect the pathophysiology of the liver by regulating the homeostasis of endobiotics. In recent years, the physiological functions of PXR and CAR in the liver have been extensively studied. Emerging evidence has suggested the roles of PXR and CAR in energy metabolism, bile acid homeostasis, cell proliferation, to name a few. This review summarizes the recent progress in our understanding of the roles of PXR and CAR in liver physiology.
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http://dx.doi.org/10.1016/j.bbadis.2021.166101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026720PMC
June 2021

LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion and immunotherapy resistance.

Sci Adv 2021 Feb 10;7(7). Epub 2021 Feb 10.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Through an integrative analysis of the lincRNA expression and tumor immune response in 9,626 tumor samples across 32 cancer types, we developed a lincRNA-based immune response (LIMER) score that can predict the immune cells infiltration and patient prognosis in multiple cancer types. Our analysis also identified tumor-specific lincRNAs, including , that potentially regulate tumor immune response in multiple cancer types. Immunocompetent mouse models and in vitro co-culture assays demonstrated that induces tumor immune evasion and resistance to immunotherapy by suppressing tumor cell antigen presentation. Mechanistically, lincRNA interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of , , , and MHC-I genes. Genetic and pharmacological inhibition of EZH2 abolish immune-related oncogenic effect and its suppression of interferon-γ signaling. The -EZH2 axis emerges as a potential mechanism for tumor immune evasion that can serve as therapeutic targets for immunotherapy.
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http://dx.doi.org/10.1126/sciadv.abb3555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875530PMC
February 2021

Small bowel obstruction post-living liver transplantation.

Am J Transplant 2021 02;21(2):898-900

Department of Surgery, Division of Transplantation, School of Medicine, University of Maryland, Baltimore, Maryland.

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http://dx.doi.org/10.1111/ajt.16303DOI Listing
February 2021

Acupoint for angina pectoris: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e24080

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province.

Introduction: Patients with angina pectoris (AP) often experience heavy psychological distress, especially anxiety and depression, which results in poorer quality of life, shorter survival time. Acupoint therapies, including massage, acupuncture, acupoints injection, acupressure, and moxibustion, showed clinical and long-lasting benefits for AP, but the efficiency of acupoint therapies was poorly evaluated. The current review is attempted to evaluate the efficacy and safety of the different acupoint-based therapies for AP.

Methods And Analysis: A literature search will be conducted in MEDLINE, EMBASE, Web of Science, Cochrane Library, Web of Science, PubMed, Science Direct, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), and China National Knowledge Infrastructure (CNKI). Observational studies regarding the association between liver cancer and depression and anxiety written in English or Chinese will be included. Study inclusion, data extraction, and quality assessment will be performed independently by 2 reviewers. We will use RevMan V.5.0 and STATA V.12.0 software for statistical analysis. The I2 test will be used to identify the extent of heterogeneity. Publication bias will be assessed by generating a funnel plot and performing the Begg and Egger test. The quality of the systematic review will be evaluated using the Measurement Tool to Assess Systematic Reviews (AMSTAR) and Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. With the permitted numeric data, we will carry out a meta-analysis.

Results: This study will provide a high-quality synthesis of pain VAS and functional disability or the quality of life, the success treatment rate, the recurrent rate and the complications rate to assess the effectiveness and safety of acupoint for AP patients. This systematic review will provide evidence to judge whether acupoint is an effective intervention for patients with AP.

Conclusion: This systematic review and meta-analysis will provide evidence to judge whether acupoint is an effective intervention for patients with AP and provide evidence for designing early targeted interventions for high-risk survivors that can attenuate negative reactions.

Prospero Registration Number: 10.17605/OSF.IO/VNXWE.
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http://dx.doi.org/10.1097/MD.0000000000024080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837901PMC
January 2021

Infection and disease spectrum in individuals with household exposure to SARS-CoV-2: A family cluster cohort study.

J Med Virol 2021 May 12;93(5):3033-3046. Epub 2021 Feb 12.

Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

We primarily quantified exposure patterns, transmission characteristics, and the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among household contacts of individuals with severe coronavirus disease-2019 (COVID-19). We conducted a retrospective cohort study of 20 index patients hospitalized with severe COVID-19 and 79 of their household contacts. We determined the transmission frequency, range of manifestations of SARS-CoV-2 infection, and factors associated with infection in household settings. Of the 79 household contacts, 53 (67%) developed SARS-CoV-2 infection (49 [62%] symptomatic, 4 [5%] asymptomatic). Eight patients (10%) developed severe COVID-19, and one died of COVID-19 pneumonia (case-fatality rate: 1.9%). The probability of SARS-CoV-2 infection was similar in children and adults (55% vs. 72%, p = .14), with children being less likely to develop the symptomatic disease (46% vs. 68%, p = .06). Handwashing ≥ 5 times/day was associated with reduced infection risk (52.8% vs. 76.9%, p = .04). SARS-CoV-2 has a high frequency of transmission among household contacts. Nonhospitalized individuals with SARS-CoV-2 infection should be quarantined in patient care facilities rather than at home to minimize spread, if possible, and frequent handwashing should be practiced to prevent transmission.
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http://dx.doi.org/10.1002/jmv.26847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014049PMC
May 2021

Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy.

Hepatol Int 2021 Feb 18;15(1):82-92. Epub 2021 Jan 18.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.

Background And Aims: Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters.

Methods: Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6 months. LRE was defined as development of decompensation, HCC or death.

Results: Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5 years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%.

Conclusion: Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.
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http://dx.doi.org/10.1007/s12072-020-10114-1DOI Listing
February 2021

Good outcomes with a bad story.

Am J Surg 2021 04 11;221(4):675-676. Epub 2021 Jan 11.

University of Maryland, School of Medicine and University of Maryland Medical Center, United States. Electronic address:

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http://dx.doi.org/10.1016/j.amjsurg.2021.01.006DOI Listing
April 2021

The efficacy and safety of lenvatinib in the treatment of solid tumors: an up-to-date meta-analysis.

Future Oncol 2021 Feb 6;17(6):745-754. Epub 2021 Jan 6.

Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, 071000, China.

We performed an updated meta-analysis to evaluate the efficacy and safety of lenvatinib in cancer patients. Databases were searched to identify relevant trials. Data were extracted to evaluate overall survival, progression-free survival, overall response rate and grade ≥3 adverse events. The pooled analysis demonstrated that lenvatinib significantly improved progression-free survival (hazard ratio: 0.43; 95% CI: 0.23-0.80; p = 0.008), overall survival (hazard ratio: 0.85; 95% CI: 0.75-0.97; p = 0.013) and overall response rate (relative risk: 6.89; 95% CI: 2.22-21.36; p = 0.001) compared with control therapy. However, the use of lenvatinib can increase the risk of severe infection. Lenvatinib-containing regimens are associated with better progression-free survival, overall survival and overall response rate, but can induce severe infection.
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http://dx.doi.org/10.2217/fon-2020-0327DOI Listing
February 2021

Genome-wide identification and analysis of sulfatase and sulfatase modifying factor genes in Bemisia tabaci (Hemiptera: Aleyrodidae).

Insect Sci 2021 Jan 5. Epub 2021 Jan 5.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

The invasive pest whitefly (Bemisia tabaci) is a complex species, of which Middle East-Minor Asia 1 (MEAM1) and Mediterranean (MED) are the two most damaging members. Previous research showed that cabbage is frequently infested with MEAM1 but seldomly with MED, and this difference in performance is associated with glucosinolate (GS) content. Some insects can modify GS using glucosinolate sulfatase (SULF), the activity of which is regulated by sulfatase modifying factor 1 (SUMF1); therefore, to increase our understanding of different performances of MEAM1 and MED on cabbage plants, we identified and compared nine putative SULFs and one SUMF in MEAM1 and MED. We found that the lengths of two genes, BtSulf2 and BtSulf4, differed between MEAM1 and MED. The messenger RNA levels of BtSulf4 increased more than 20-fold after MEAM1 and MED adults were exposed to GS, but BtSulf2 expression was only induced by GS in MEAM1. Knockdown of BtSulf2 and BtSulf4 in MEAM1 resulted in a substantial increase in the mortality of GS-treated adults but not in MED. These results indicate that differences in BtSulf2 and BtSulf4 sequences and/or expression may explain why MEAM1 performs better than MED on cabbage. Our results provide a basis for future functional research on SULF and SUMF in B. tabaci.
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http://dx.doi.org/10.1111/1744-7917.12898DOI Listing
January 2021

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

JGH Open 2020 Dec 15;4(6):1065-1073. Epub 2020 Jul 15.

Department of Infectious Diseases Merck & Co., Inc. Kenilworth New Jersey USA.

Background And Aim: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.

Methods: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067).

Results: A total of 152 participants in China were randomly assigned (ITG, = 115; DTG, = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, = 3; GT6a, = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo.

Conclusion: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.
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http://dx.doi.org/10.1002/jgh3.12387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731814PMC
December 2020

Altered neural activity in the reward-related circuit and executive control network associated with amelioration of anhedonia in major depressive disorder by electroconvulsive therapy.

Prog Neuropsychopharmacol Biol Psychiatry 2020 Dec 5;109:110193. Epub 2020 Dec 5.

Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China; Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Anhui Province, China; Institute of Artificial Intelligence, University of Science and Technology of China, Hefei, Anhui Province, China.

Anhedonia is a core characteristic of depression, the amelioration of which accounts for depressive symptom improvement. Electroconvulsive therapy (ECT) has been shown remarkable antidepressive effect, however, less is known about the effect of ECT on anhedonia and its underlying neural mechanism. Herein, we investigated local and global intrinsic brain functional alterations during the resting state in 46 patients with pre- and post-ECT major depressive disorder using the amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) approach. Functional connectivity (FC) was also calculated between nodes with significant local and global intrinsic brain functional alterations. The severity of anhedonia and depression was assessed with the Temporal Experience of Pleasure Scale and Hamilton Depression Rating Scale, respectively. The relationship between the change in anhedonia and depressive symptoms and brain functional alterations was determined. Increased ALFF and DC were observed in the bilateral dorsal medial prefrontal cortex (dmPFC), right dorsal lateral prefrontal cortex (dlPFC), left orbitofrontal cortex, and right orbitofrontal cortex (ROFC) after ECT. Correlational analysis between the change in anhedonia and ALFF had positive results in the dmPFC. Similarly, there was a positive correlation between the change in anhedonia and change in DC in the dmPFC, right dlPFC, ROFC, and middle frontal gyrus. Furthermore, there was a significant relationship between the change in anhedonia and altered dmPFC-dlPFC FC. These results revealed that amelioration of anhedonia may be associated with intrinsic neural activity alteration in the reward-related circuit and executive control network following ECT.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110193DOI Listing
December 2020

Screening varices in patients with HBV-related cirrhosis on antiviral therapy: Platelet alone or together with LSM.

Liver Int 2021 02 18;41(2):369-377. Epub 2020 Dec 18.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Diseases, Beijing, China.

Background & Aims: Non-invasive assessment criteria to rule out high-risk varices (HRV) in compensated hepatitis B virus (HBV) cirrhosis on antiviral therapy remains unclear.

Methods: HBV-related compensated cirrhotic patients who underwent screening endoscopy during antiviral therapy were enrolled and randomly divided into the derivation and validation sets. HRV were defined as medium to large varices or small varices with red signs. Univariate and multivariate logistic analysis were used to determine the parameters associated with HRV.

Results: A total of 436 HBV-related compensated cirrhotic patients screened for varices were enrolled, the median duration of antiviral therapy was 4 years (IQR: 2.5-5.5 years). In the derivation set (N = 290, 17.2% with HRV), only platelet (PLT) count (OR = 0.972, 95% CI 0.961-0.984, P < .05) was independently associated with HRV, whereas liver stiffness measurement was not associated with the presence of HRV. With a PLT count cut-off value of 105 × 10 /L, unnecessary endoscopies could be spared in 56.9% patients, with a 3.6%. risk of missing HRV. In the validation cohort (N = 146, 16.4% with HRV), the proportion of patients that could safely spare endoscopies (61.0%) identified by this PLT count cut-off value was higher than that obtained by using Baveno VI criteria (34.9%), with an acceptable risk of missing HRV (3.4%).

Conclusion: Compared with the 'Baveno VI criteria or beyond' criteria, PLT count higher than 105 × 10 /L could safely spare more screening endoscopies without increasing the risk of missing HRV in patients with HBV-related compensated cirrhosis on antiviral therapy.
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http://dx.doi.org/10.1111/liv.14752DOI Listing
February 2021