Publications by authors named "Hong You"

358 Publications

The Influence of Different Operation Conditions on the Treatment of Mariculture Wastewater by the Combined System of Anoxic Filter and Membrane Bioreactor.

Membranes (Basel) 2021 Sep 24;11(10). Epub 2021 Sep 24.

School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

The mariculture wastewater treatment performance for the combined system of anoxic filter and membrane bioreactor (AF-MBR) was investigated under different hydraulic retention times (HRTs), influent alkalinity, and influent ammonia nitrogen load. The results showed that the removal efficiencies of TOC and total nitrogen were slightly better at the HRT of 8 h than at other HRTs, and the phosphate removal efficiency decreased with the increase of HRT. With the increase of influent alkalinity, the removal of TOC and phosphate did not change significantly. With the increase of influent alkalinity from 300 mg/L to 500 mg/L, the total nitrogen removal efficiency of AF-MBR was improved, but the change of the removal efficiency was not obvious when the alkalinity increased from 500 mg/L to 600 mg/L. When the influent concentration of ammonia nitrogen varied from 20 mg/L to 50 mg/L, the removal efficiencies of TOC, phosphate, and total nitrogen by AF-MBR were stable. An interesting finding was that in all the different operation conditions examined, the treatment efficiency of AF-MBR was always better than that of the control MBR. The concentrations of NO-N in AF-MBR were relatively low, whereas NO-N accumulated in the control MBR. The reason was that the microorganisms attached to the carrier and remained fixed in the aerobic and anoxic spaces, so that there was a gradual enrichment of bacteria characterized by slow growth in a high-salt environment. In addition, the microorganisms could gather and grow on the carrier forming a biofilm with higher activity, a richer and more stable population, and enhanced ability to resist a load impact.
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http://dx.doi.org/10.3390/membranes11100729DOI Listing
September 2021

Changing clinical care cascade of patients with chronic hepatitis B in Beijing, China.

Lancet Reg Health West Pac 2021 Nov 25;16:100249. Epub 2021 Aug 25.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Background: High uptake of hepatitis B virus (HBV) tests and antiviral therapy are required to improve the clinical outcomes of patients with chronic hepatitis B (CHB) at the population level. In the current study, we used the Basic Medical Care Insurance for Employees (BMCIE) to investigate the changes of clinical care cascade of CHB in Beijing, China.

Methods: Records for medical service of CHB patients from January 1, 2010 to December 31, 2018 were retrieved from the BMCIE database. The annual and cumulative rates of CHB patients in care, receiving HBV tests and on antiviral therapy were calculated. The trends of annual percentage changes (APCs) were estimated using Joinpoint regression model.

Findings: Among estimated HBsAg positive employees, the rate of CHB patients in care increased from 4•77% in 2010 to 18•61% in 2018 (APC=17•3, 95%CI: 14•4-20•4). The rate of HBV tests increased from 4•41% in 2010 to 16•39% in 2018. Among the estimated eligible employees for treatment, the rate of antiviral therapy increased from 3•92% in 2010 to 30•88% in 2018. The proportion of hospital visits for HBV≥4 times per year had increased from 47•07% in 2010 to 65•31% in 2018. By 2018, entecavir (65•07%) and tenofovir (12•98%) had become the predominantly prescribed antiviral agents.

Interpretation: The rates of CHB patients in care, receiving HBV tests and on antiviral therapy substantially increased in Beijing, China. However, more efforts are still needed to increase the uptake of HBV tests and treatment for achieving the goal of HBV elimination by 2030.

Funding: Beijing Municipal Science and Technology Commission (No.D161100002716003), National Science and Technology Major Special Project for Infectious Diseases (No.Z191100007619037, No.2018ZX10302204), and Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXX 0104).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406027PMC
November 2021

Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China.

Orphanet J Rare Dis 2021 09 28;16(1):398. Epub 2021 Sep 28.

Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis , Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing, 100050, China.

Background: Hereditary hemochromatosis (HH) is widely recognized and clinical manifestations of hemochromatosis-related (HFE-related) HH is well studied in European populations. Less is known about the clinical and laboratory characteristics of non-HFE related HH in Asian population. We aimed to explore the relationship between genotype and clinical phenotype in Chinese patients with non-HFE related hereditary hemochromatosis.

Methods: Peripheral blood samples and clinical data of patients with primary iron overload were collected from the China Registry of Genetic/Metabolic Liver Diseases. Sanger sequencing was performed in cases with primary iron overload, for 5 known HH related genes (HFE, HJV, HAMP, TFR2 and SLC40A1) and 2 novel iron homeostasis-related genes (DENND3 and SUGP2). The correlation of genotype and clinical phenotype in these patients was analyzed.

Results: Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%), including 8 pathogenic variants in HJV, 7 pathogenic variants in SLC40A1, 8 likely pathogenic variants in SUGP2 and 5 likely pathogenic variants in DENND3 cases. Among these 31 cases, 4 cases harbored homozygous variants, 2 cases harbored homozygous + heterozygous variants, 19 cases harbored heterozygous or combined heterozygous variants, and 6 cases harbored no any damaging variants. None of investigated cases carried damaging HAMP and TFR2 variants were found. 8 cases were classified as type 2A HH and 6 cases as type 4 HH, 10 cases as non-classical genotype, and 6 cases had no pathogenic variants from 31 cases. During the statistical analysis, we excluded one case (SLC40A1 IVS3 + 10delGTT + SUGP2 p. R639Q(homo)) with difficulty in grouping due to combined damaging variants. Cases with type 2A HH have an earlier age at diagnosis (p = 0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p = 0.01). Arthropathy was relatively rare in all groups. None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p = 0.011), cardiac involvement (p = 0.042), diabetes (p = 0.035) and hypogonadism (p = 0.020) was statistically significant in the four groups. However, due to the limited sample size, the pairwise comparison showed no significant difference.

Conclusions: This is the first comprehensive analysis about the gene variant spectrum and phenotypic aspects of non-HFE HH in China. The results will be useful to the identification, diagnosis and management of HH in China.
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http://dx.doi.org/10.1186/s13023-021-02020-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479922PMC
September 2021

Selective depletion of hepatic stellate cells-specific LOXL1 alleviates liver fibrosis.

FASEB J 2021 10;35(10):e21918

Beijing Clinical Medicine Institute, Beijing, P.R. China.

The role of LOXL1 in fibrosis via mediating ECM crosslinking and stabilization is well established; however, the role of hepatic stellate cells (HSCs)-specific LOXL1 in the development of fibrosis remains unknown. We generated HSCs-specific Loxl1-depleted mice (Loxl1 mice) to investigate the HSCs-specific contribution of LOXL1 in the pathogenesis of fibrosis. Loxl1 mice were used as the control. Furthermore, we used RNA sequencing to explore the underlying changes in the transcriptome. Results of the sirius red staining, type I collagen immunolabeling, and hydroxyproline content analysis, coupled with the reduced expression of profibrogenic genes revealed that Loxl1 mice with CCl -induced fibrosis exhibited decreased hepatic fibrosis. In addition, Loxl1 mice exhibited reduced macrophage tissue infiltration by CD68-positive cells and decreased expression of inflammatory genes compared with the controls. RNA sequencing identified integrin α8 (ITGA8) as a key modulator of LOXL1-mediated liver fibrosis. Functional analyses showed that siRNA silencing of Itga8 in cultured fibroblasts led to a decline in the LOXL1 expression and inhibition of fibroblast activation. Mechanistic analyses indicated that LOXL1 activated the FAK/PI3K/AKT/HIF1a signaling pathway, and the addition of inhibitors of FAK or PI3K reversed these results via downregulation of LOXL1. Furthermore, HIF1a directly interacted with LOXL1 and upregulated its expression, indicating that LOXL1 can positively self-regulate by forming a positive feedback loop with the FAK/PI3K/AKT/HIF1a pathway. We demonstrated that HSCs-specific Loxl1 deficiency prevented fibrosis, inflammation and that ITGA8/FAK/PI3K/AKT/HIF1a was essential for the function and expression of LOXL1. Knowledge of this approach can provide novel mechanisms and targets to treat fibrosis in the future.
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http://dx.doi.org/10.1096/fj.202100374RDOI Listing
October 2021

Preparation and Characterization of MWCNTs/PVDF Conductive Membrane with Cross-Linked Polymer PVA and Study on Its Anti-Fouling Performance.

Membranes (Basel) 2021 Sep 14;11(9). Epub 2021 Sep 14.

State Key Laboratory of Urban Water Resources and Water Environment, School of Marine Science and Technology, Harbin Institute of Technology at Weihai, Weihai 264200, China.

Based on carboxylated multi-walled carbon nanotubes (MWCNTs-COOH), a MWCNTs/PVDF conductive membrane was prepared by a vacuum filtration cross-linking method. The surface compositions and morphology of conductive membranes were studied by X-ray photoelectron spectroscopy and high-resolution field emission scanning electron microscopy, respectively. The effects of cross-linked polymeric polyvinyl alcohol (PVA) on the conductive membrane properties such as the porosity, pore size distribution, pure water flux, conductivity, hydrophilicity, stability and antifouling properties were investigated. Results showed that the addition of PVA to the MWCNTs/PVDF conductive membrane decreased the pure water flux, porosity and the conductivity. However, the hydrophilicity of the modified MWCNTs/PVDF conductive membrane was greatly improved, and the contact angle of pure water was reduced from 70.18° to 25.48° with the addition of PVA contents from 0 wt% to 0.05 wt%. Meanwhile, the conductive membranes with higher content had a relatively higher stability. It was found that the conductive functional layer of the conductive membrane had an average mass loss rate of 1.22% in the 30 min ultrasonic oscillation experiment. The tensile intensity and break elongation ratio of the conductive membrane are improved by the addition of PVA, and the durability of the conductive membrane with PVA was superior to that without PVA added. The electric assisted anti-fouling experiments of modified conductive membrane indicated that compared with the condition without electric field, the average flux attenuation of the conductive membrane was reduced by 11.2%, and the membrane flux recovery rate reached 97.05%. Moreover, the addition of PVA could accelerate the clean of the conductive membranes.
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http://dx.doi.org/10.3390/membranes11090703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464980PMC
September 2021

Ultrasonic role to activate persulfate/chlorite with foamed zero-valent-iron: Sonochemical applications and induced mechanisms.

Ultrason Sonochem 2021 Oct 10;78:105750. Epub 2021 Sep 10.

State Key Laboratory of Urban Water Resources and Environment, Harbin Institute of Technology, Harbin 150090, China.

The novel system, consisting of composite oxidants (persulfate/chlorite, SO/ClO) and stationary phase activator (zero-valent-iron foam, Fe) driven by ultrasonic (US) field, was applied to treat the triphenylmethane derivative effectively even at low temperature (≈ 289 K). By comparisons of sub-systems, the US roles to SO, ClO, and Fe were seriatim analyzed. US made the reaction order of multi-component system tend to within 1 (leading to de-order reaction), and widened pH activating range of the Fe by sonicate-polishing during the process of ClO co-activating SO. US and Fe were affected by fluid eddy on activating SO/ClO. The Fe had slight effect on the temperature of US bubble-water interface but the addition of ClO lowered it. The partitioning capacity of the above US reactive zone increased during the reaction. US and ClO could enrich the kinds of degradation intermediates. The contributions of free radicals (ClO-based radicals, sulfate radicals (SO), and hydroxyl radicals (OH)) and non-free radicals (ClO, and O = Fe from ionic Fe under "-O-O-" of SO and cyclic adjustment reaction of ClO) processes by sonochemical induction were equally important by corresponding detection means. Especially, real-time and online high-resolution mass spectrum by self-developing further confirmed the chain transfers of different free radicals due to US role. The findings expanded the application of sono-persulfate-based systems and improved understanding on activation mechanism.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455865PMC
October 2021

The Matrisome Genes From Hepatitis B-Related Hepatocellular Carcinoma Unveiled.

Hepatol Commun 2021 Sep 16;5(9):1571-1585. Epub 2021 Jun 16.

Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.

Chronic hepatitis B virus (HBV) infection changes the composition of the extracellular matrix (ECM) and enables the onset and progression of hepatocellular carcinoma (HCC). The ensemble of ECM proteins and associated factors is a major component of the tumor microenvironment. Our aim was to unveil the matrisome genes from HBV-related HCC. Transcriptomic and clinical profiles from 444 patients with HBV-related HCC were retrieved from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) repositories. Matrisome genes associated with HBV-related hepatocarcinogenesis, matrisome gene modules, HCC subgroups, and liver-specific matrisome genes were systematically analyzed, followed by identification of their biological function and clinical relevance. Eighty matrisome genes, functionally enriched in immune response, ECM remodeling, or cancer-related pathways, were identified as associated with HBV-related HCC, which could robustly discriminate HBV-related HCC tumor from nontumor samples. Subsequently, four significant matrisome gene modules were identified as showing functional homogeneity linked to cell cycle activity. Two subgroups of patients with HBV-related HCC were classified based on the highly correlated matrisome genes. The high-expression subgroup (15.0% in the TCGA cohort and 17.9% in the GEO cohort) exhibited favorable clinical prognosis, activated metabolic activity, exhausted cell cycle, strong immune infiltration, and lower tumor purity. Four liver-specific matrisome genes (F9, HPX [hemopexin], IGFALS [insulin-like growth-factor-binding protein, acid labile subunit], and PLG [plasminogen]) were identified as involved in HBV-related HCC progression and prognosis. Conclusion: This study identified the expression and function of matrisome genes from HBV-related hepatocarcinogenesis, providing major insight to understand HBV-related HCC and develop potential therapeutic opportunities.
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http://dx.doi.org/10.1002/hep4.1741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435279PMC
September 2021

Analytical strategies to determine the labelling accuracy and economically-motivated adulteration of "natural" dietary supplements in the marketplace: Turmeric case study.

Food Chem 2021 Sep 1;370:131007. Epub 2021 Sep 1.

Global Curcumin Association, 18 Augusta Pines Dr, Suite 151 West #2, Spring, TX 77389, USA. Electronic address:

Turmeric has faced authenticity issues as instances of economic-adulterations to reduce the cost. We used carbon-14 and HPLC analyses as complementary methods to verify "all-natural" label claims of commercial dietary supplements containing turmeric ingredients. A high percentage of curcumin-to-curcuminoids value was used as an indicator to imply the presence of synthetic curcumin. However, using the HPLC method alone did not provide direct evidence of curcuminoids' natural origin, whereas using only the carbon-14 method cannot test for potency label claims and determine which constituent(s) contain C radiocarbon. By analyzing results from both methods, a significant correlation between the percentage of curcumin-to-curcuminoids and % biobased carbon (Pearson's r = -0.875, p < 0.001) indicated that synthetic curcumin was greatly attributed to determined synthetic ingredients. Only four out of the 14 samples analyzed supported authentic label claims. This orthogonal testing strategy showed its potential for the quality control of turmeric products.
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http://dx.doi.org/10.1016/j.foodchem.2021.131007DOI Listing
September 2021

Fascin promotes the invasion of pituitary adenoma through partial dependence on epithelial-mesenchymal transition.

J Mol Histol 2021 Aug 7;52(4):823-838. Epub 2021 Jun 7.

Department of Neurosurgery, The First Affiliated Hospital, Shihezi University School of Medicine, North 2 Road, Shihezi, 832000, Xinjiang, China.

The aim of the present study was to investigate the role and potential regulatory mechanisms of fascin in the invasion and epithelial-to-mesenchymal transition of pituitary adenoma cells. A total of 30 specimens were assessed in the present study. The expression levels of fascin in the invasive pituitary adenoma group and non-invasive pituitary adenoma group were determined by immunochemistry. Fascin was downregulated via small interfering RNA in mouse pituitary AtT-20 cells. The proliferation, cell cycle and apoptosis of AtT-20 cells were assessed using Cell Counting Kit‑8 and flow cytometry. The invasion of AtT-20 cells was detected using a Transwell assay. Transmission electron microscopy was utilized to observe the ultrastructure of AtT-20 cells. Real-time quantitative PCR, Western blotting and immunofluorescence staining were utilized to detect the expression levels of fascin and EMT markers. In the present study, fascin expression and clinical characteristics were not significantly correlated in pituitary adenoma. The protein expression level of fascin in invasive pituitary adenoma was higher than that in non-invasive pituitary adenoma, as assessed by immunochemistry. Downregulation of fascin resulted in significant decreases in cell viability, proliferation and invasion, arrested the cell cycle at the G1 phase and increased apoptosis. In addition, downregulation of fascin significantly decreased the expression levels of N-cadherin, the mesenchymal cell marker vimentin and the transcription factor Twist but significantly increased the expression levels of the epithelial cell marker E-cadherin. Further experiments revealed that overexpression of E-cadherin resulted in significant decreases in cell viability, proliferation, invasion, and the expression of fascin and transcription factor Twist and also arrested the cell cycle at the G2 phase. The results of the present study suggest that suppressing the expression level of fascin could regulate the invasion, proliferation and apoptosis of pituitary tumour cells and alter the expression level of various EMT markers. The present study identified that fascin effectively promotes the invasion, proliferation and apoptosis of pituitary tumour cells partially via the EMT pathway.
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http://dx.doi.org/10.1007/s10735-021-09995-9DOI Listing
August 2021

Hepatic stellate cells-specific LOXL1 deficiency abrogates hepatic inflammation, fibrosis, and corrects lipid metabolic abnormalities in non-obese NASH mice.

Hepatol Int 2021 Oct 20;15(5):1122-1135. Epub 2021 May 20.

Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing, 100050, People's Republic of China.

Background And Aims: Lysyl oxidase-like-1 (LOXL1), a vital cross-linking enzyme in extracellular matrix (ECM) maintenance, promotes fibrosis via enhancement of ECM stability. However, the potential role of LOXL1 in the pathogenesis of nonalcoholic steatohepatitis (NASH) has not been previously studied.

Methods: We generated Loxl1 mice to selectively delete LOXL1 in hepatic stellate cells (HSCs) (Loxl1Gfap; Loxl1 as littermate controls) and then examined liver pathology and metabolic profiles in Loxl1Gfap fed with either a choline-deficient L-amino acid-defined (CDAA) diet or an isocaloric control diet for 16 weeks. Thereafter, the findings from the animal model were confirmed in 23 patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD).

Results: LOXL1 was significantly increased in CDAA induced non-obese NASH compared with the control diet, and LOXL1 deficient in HSCs ameliorated CDAA-induced inflammation and fibrosis, with reduced expression of pro-inflammation and pro-fibrogenic genes in the HSCs-specific LOXL1 knockout mice model. Interestingly, LOXL1 deficient in HSCs could attenuate hepatic steatosis and reverse the metabolic disorder by restoring adipose tissue function without altering the effect of hepatic lipogenesis gene expression in non-obese NASH model. More importantly, analyses of serum LOXL1 and leptin levels from NAFLD patients revealed that LOXL1 was positively correlated with histological fibrosis progression, whereas it was inversely correlated with leptin levels, especially in non-obese NAFLD patients.

Conclusion: LOXL1 may contribute to fibrosis progression in non-obese NAFLD, and HSCs-specific knockout of LOXL1 attenuated liver steatosis, inflammation, fibrosis, , and improved lipid metabolic abnormalities. Hence, LOXL1 inhibition may serve as a new therapeutic strategy for NASH.
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http://dx.doi.org/10.1007/s12072-021-10210-wDOI Listing
October 2021

Lateral ventricular medulloepithelioma in children: a case report.

Transl Pediatr 2021 Apr;10(4):1020-1025

Department of Neurosurgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.

Medulloepithelioma is an extremely rare highly malignant and rapidly growing tumor that occurs in the central nervous system. There are few reports of medulloepithelioma located in the ventricle. Medulloepithelioma is common in young children and adolescence. Herein, we described an unusual case of vomiting in a 4-year-old male patient with medulloepithelioma, presenting with enlarging head circumference. Because of computed tomography (CT) scan of the head showed signs of brain tumors and hydrocephalus, and enhanced magnetic resonance imaging (MRI) sequence showed increased heterogeneity and honeycomb-like changes on the mass after the administration of a contrast agent, the patient was first diagnosed as choroid plexus papilloma. After undergoing a surgical craniotomy, the patient was diagnosed as medulloepithelioma through pathological examination. We hope that this work will provide more understanding and knowledge of intracranial medulloepithelioma. For medulloepithelioma that occurs in the central nervous system, radiological examination is not sufficient to make a definite diagnosis of the tumor. Pathological examination can confirm the diagnosis of medulloepithelioma and distinguish it from other central system tumors. Surgical resection is a safe and effective method that can prolong the life of patients. However, the prognosis of medulloepithelioma is still poor, and further research is needed to improve the diagnosis and treatment of this rare disease.
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http://dx.doi.org/10.21037/tp-20-257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107848PMC
April 2021

Sound therapy can modulate the functional connectivity of the auditory network.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 7;110:110323. Epub 2021 Apr 7.

Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address:

The functional connectivity of the auditory network is considered to be important in the development of tinnitus. We hypothesized that sound therapy, as a commonly used effective treatment for tinnitus, can modulate the functional connectivity of the auditory network. In this prospective observational study, we recruited 27 tinnitus patients who had undergone 12 weeks of sound therapy and 27 matched healthy controls. For the two groups of subjects, resting-state functional magnetic resonance imaging was acquired both at baseline and at the 12th week. We utilized independent component analysis and seed-based functional connectivity analysis to characterize the connectivity features of the auditory network. Interaction effects between the two groups and the two scans within the auditory network were observed, which were driven by increased functional connectivity in the left primary auditory cortex (PAC) and decreased values in the secondary auditory cortex (SAC) in tinnitus patients after treatment. Increased connections between the auditory network and limbic network, as well as decreased values with the bilateral thalami, were identified. The effects were mainly driven by the functional connectivity alterations of the SAC rather than that of the PAC. Significant positive correlations between the percent improvement in the Tinnitus Handicap Inventory (THI) score and the percentage change rates of functional connectivity between the SAC and bilateral thalami were observed. Our study contributes to the understanding of the mechanism of tinnitus and effective sound therapy, providing evidence to support the theory of a gain adaptation mechanism that quantifies the recovered gating function of the thalamus in tinnitus patients.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110323DOI Listing
August 2021

Alteration of -Methyladenosine mRNA Methylation in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

Front Neurosci 2021 16;15:605654. Epub 2021 Mar 16.

Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.

Aim: This study was conducted in order to reveal the alterations in the -methyladenosine (m6A) modification profile of cerebral ischemia-reperfusion injury model rats.

Materials And Methods: Rats were used to establish the middle cerebral artery occlusion and reperfusion (MCAO/R) model. MeRIP-seq and RNA-seq were performed to identify differences in m6A methylation and gene expression. The expression of m6A methylation regulators was analyzed in three datasets and detected by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence.

Results: We identified 1,160 differentially expressed genes with hypermethylated or hypomethylated m6A modifications. The differentially expressed genes with hypermethylated m6A modifications were involved in the pathways associated with inflammation, while hypomethylated differentially expressed genes were related to neurons and nerve synapses. Among the m6A regulators, FTO was specifically localized in neurons and significantly downregulated after MCAO/R.

Conclusion: Our study provided an m6A transcriptome-wide map of the MACO/R rat samples, which might provide new insights into the mechanisms of cerebral ischemia-reperfusion injury.
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http://dx.doi.org/10.3389/fnins.2021.605654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009187PMC
March 2021

Innovations and Advances in Schistosome Stem Cell Research.

Front Immunol 2021 5;12:599014. Epub 2021 Mar 5.

Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.
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http://dx.doi.org/10.3389/fimmu.2021.599014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973109PMC
June 2021

Comparison of fibrosis regression of entecavir alone or combined with pegylated interferon alpha2a in patients with chronic hepatitis B.

Hepatol Int 2021 Jun 7;15(3):611-620. Epub 2021 Mar 7.

Liver Research Center, Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis, Beijing Friendship Hospital, National Clinical Research Center of Digestive Diseases, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.

Background And Aims: Antiviral treatment with necleos(t)ide analogues contributes to histological improvement and virologic response in chronic hepatitis B (CHB) patients. However, whether adding pegylated interferon alpha2a (Peg-IFN-α-2a) can help additional clinical benefit, particularly on fibrosis regression was still unknown.

Methods: Chronic hepatitis B patients with pre-treatment biopsy-proven Ishak fibrosis score 2, 3 or 4 were randomly assigned to entecavir (ETV) alone or ETV plus Peg-IFN-α-2a (Peg-IFN-α-2a add-on) group (1:2 ratio). Post-treatment liver biopsy was performed at week 78. Fibrosis regression was defined as decrease in Ishak fibrosis score by ≥ 1 stage or predominantly regressive categorized by P-I-R score. Serum HBV DNA levels were assessed at baseline and every 26 weeks, while HBsAg and HBeAg were evaluated at baseline and every 52 weeks.

Results: A total of 218 treatment-naive CHB patients were randomly assigned to ETV alone or Peg-IFN-α-2a add-on group. Totals of 155 patients (ETV alone: Peg-IFN-α-2a add-on, 47:108) were included in statistical analysis. Fibrosis regression rates were 68% (32/47) in the ETV alone and 56% (60/108) in Peg-IFN-α-2a add-on group (p = 0.144). Both groups showed a similar trend of virological suppression during the process of 104-week antiviral therapy (p = 0.132). HBeAg or HBsAg loss or seroconversion rates in the ETV alone group were lower than Peg-IFN-α-2a add-on group though without statistical significance.

Conclusions: Peg-IFN-α-2a add-on therapy did not yield additional fibrosis regression and virologic response than ETV alone therapy.
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http://dx.doi.org/10.1007/s12072-021-10162-1DOI Listing
June 2021

Aquaculture drug degradation in persulfate by PANI-based microparticles controlled via ultrasonic field: Forced motion of "burning hot micromotors".

Chemosphere 2021 Jul 23;275:130098. Epub 2021 Feb 23.

School of Marine Science and Technology, Harbin Institute of Technology at Weihai, Weihai, 264209, China.

The triphenylmethane derivative malachite green (tpm) despite repeated prohibitions but is frequently detected in aquatic environment and draws emerging attention because of the potential poisonous effects. The polyaniline/persulfate with ultrasound catalysis (US/PANI-PS) was developed for tpm removal. The effects of 12 factors and the optimization by response surface methodology (RSM) for tpm removal were evaluated based on the pseudo-first-kinetics (k). From free radical inhibition, the ratios of active species in US/PANI-PS (δ = 0.355, δ = 0.593) were close to that in US-PS (δ = 0.346, δ = 0.586) and different to that in PANI-PS and PS systems. A possible degradation pathway (hydroxylation, N-demethylation, deamination, and open-benzene ring) was explored by gas chromatography-mass spectrometer (GC/MS) and high performance liquid chromatography-mass spectrometer (HPLC-MS). The designed reactor involving the US-driven PANI was simulated by acoustic-piezoelectric interaction. From cavitation calculations, the estimated effective-mean temperature at bubble-water interface had little increasing (from 704 K to 711 K) after adding the PANI, however, the adsorption capacity of tpm in reactive zone decreased from 0.0891 μM to 0.0787 μM. The mechanism (PANI hot turbo-micromotors) with US/PANI-PS was proposed. The tpm was removed with a low treatment cost of 2.81 $⋅m (the EE/O value 18.29 kWh⋅m) by US/PANI-PS, presenting a cost-effective treating process. The reusability tests and characterizations (contact angle, X-ray diffraction (XRD), and scanning electron microscope (SEM)) further confirmed the stability of PANI.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130098DOI Listing
July 2021

Hepatocellular Carcinoma Prediction Models in Chronic Hepatitis B: A Systematic Review of 14 Models and External Validation.

Clin Gastroenterol Hepatol 2021 Mar 3. Epub 2021 Mar 3.

National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Background & Aims: The aim of our study was to characterize the performance of hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients through meta-analysis followed by external validation.

Methods: We performed a systematic review and meta-analysis of current literature, followed by external validation in independent multi-center cohort with 986 patients with CHB undergoing entecavir treatment (median follow-up: 4.7 years). Model performance to predict HCC within 3, 5, 7, and 10 years was assessed using area under receiver operating characteristic curve (AUROC) and calibration index. Subgroup analysis were conducted by treatment status, cirrhotic, race and baseline alanine aminotransferase.

Results: We identified 14 models with 123,885 patients (5,452 HCC cases), with REACH-B, CU-HCC, GAG-HCC, PAGE-B and mPAGE-B models being broadly externally validated. Discrimination was generally acceptable for all models, with pooled AUC ranging from 0.70 (95% CI, 0.63-0.76 for REACH-B) to 0.83 (95% CI, 0.78-0.87 for REAL-B) for 3-year, 0.68 (95% CI, 0.64-0.73 for REACH-B) to 0.81 (95% CI, 0.77-0.85 for REAL-B) for 5-year and 0.70 (95% CI, 0.58-0.80 for PAGE-B) to 0.81 (95% CI, 0.78-0.84 for REAL-B and 0.77-0.86 for AASL-HCC) for 10-year prediction. However, calibration performance was poorly reported in most studies. In external validation cohort, REAL-B showed highest discrimination with 0.76 (95% CI, 0.69-0.83) and 0.75 (95% CI, 0.70-0.81) for 3 and 5-year prediction. The REAL-B model was also well calibrated in the external validation cohort (3-year Brier score 0.066). Results were consistent in subgroup analyses.

Conclusions: In a systematic review of available HCC models, the REAL-B model exhibited best discrimination and calibration.
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http://dx.doi.org/10.1016/j.cgh.2021.02.040DOI Listing
March 2021

Microbial community dynamic shifts associated with sulfamethoxazole degradation in microbial fuel cells.

Chemosphere 2021 Jul 22;274:129744. Epub 2021 Jan 22.

State Key Laboratory of Urban Water Resource and Environment (SKLUWRE), School of Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

Though sulfamethoxazole (SMX) degradation at the low or medium concentration (SMX< 30 mg/L) has been reported in the microbial fuel cell (MFC), further exploration is still urgently required to investigate how the high concentration of SMX affect the anode biofilm formation. In this study, the degradation mechanism of SMX and the response of microbial community to SMX at different initial concentrations (0, 0.5, 5 and 50 mg/L) were investigated in MFCs. The highest SMX removal efficiency of 98.4% was obtained in MFC (5 mg/L). SMX at optimal concentration (5 mg/L) could serve as substrate accelerating the extracellular electron transfer. However, high concentration of SMX (50 mg/L) conferred significant inhibition on the electron transfer with SMX removal decline to 84.4%. The 16S rRNA high-throughput sequencing revealed the significant shift of the anode biofilms communities with different initial SMX concentrations were observed in MFCs. Thauera and Geobacter were the predominant genus, with relative abundance of 31.9% in MFC (50 mg/L SMX) and 52.7% in MFC (5 mg/L SMX). Methylophilus exhibited a huge increase with the highest percentage of 16.4% in MFC (50 mg/L). Hence, the functional bacteria of Thauera, Geobacter and Methylophilus endowed significant tolerance to the selection pressure from high concentration of SMX in MFCs. Meanwhile, some bacteria including Ornatilinea, Dechloromonas and Longilinea exhibited a decrease or even disappeared in MFCs. Therefore, initial concentrations of SMX played a fundamental role in modifying the relative abundance of predominant populations. This finding would promote theories support for understanding the evolution of anode biofilm formation related to the different initial concentrations of SMX in MFCs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129744DOI Listing
July 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

14-kDa phosphohistidine phosphatase is a potential therapeutic target for liver fibrosis.

Am J Physiol Gastrointest Liver Physiol 2021 03 6;320(3):G351-G365. Epub 2021 Jan 6.

Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

Liver fibrosis, a major cause of morbidity and mortality worldwide, leads to liver damage, seriously threatening human health. In our previous study, we demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) was upregulated in fibrotic liver tissue and involved in the migration and lamellipodia formation of hepatic stellate cells (HSCs). In this study, we evaluated PHP14 as a therapeutic target for liver fibrosis and investigated the mechanism by which it mediates liver fibrosis. AAV-sh administration significantly attenuates CCl-induced liver fibrosis in mice. In particular, fibrosis-associated inflammatory infiltration was significantly suppressed after PHP14 knockdown. Mechanistically, PHP14 regulated macrophage recruitment, infiltration, and migration by affecting podosome formation of macrophages. Inhibition of PHP14 decreased the expression of the fibrogenic signature at the early stage of liver fibrogenesis and the activation of HSCs in vivo. Thus, PHP14 can be considered a potential therapeutic target for liver fibrosis. PHP14 inhibition via adeno-associated virus (AAV)-mediated gene silencing could potently attenuate carbon tetrachloride (CCl)-induced liver fibrosis. PHP14 could regulate the migration of macrophages to the site of injury in vivo. PHP14 knockdown in vivo influenced the environment of fibrogenesis and relevant signaling pathways, subsequently affecting myofibroblast activation.
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http://dx.doi.org/10.1152/ajpgi.00334.2020DOI Listing
March 2021

New understanding of novel brominated flame retardants (NBFRs): Neuro(endocrine) toxicity.

Ecotoxicol Environ Saf 2021 Jan 13;208:111570. Epub 2020 Nov 13.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

Traditional brominated flame retardants (BFRs) negatively affect the environment and human health, especially in the sensitive (developing) nervous system. Considering the physicochemical similarities between novel brominated flame retardants (NBFRs) and BFRs, more and more evidence reveals the neurotoxic effects of NBFRs. We reviewed the neuro(endocrine) toxic effects of NBFRs in vivo and in vitro and discussed their action mechanisms based on the available information. The neurotoxic potential of NBFRs has been demonstrated through direct neurotoxicity and disruption of the neuroendocrine system, with adverse effects on neurobehavioral and reproductive development. Mechanistic studies have shown that the impact of NBFRs is related to the complex interaction of neural and endocrine signals. From disrupting the gender differentiation of the brain, altering serum thyroid/sex hormone levels, gene/protein expression, and so on, to interfere with the feedback effect between different levels of the HPG/HPT axis. In this paper, the mechanism of neurotoxic effects of NBFRs is explored from a new perspective-neuro and endocrine interactions. Gaps in the toxicity data of NBFRs in the neuroendocrine system are supplemented and provide a broader dataset for a complete risk assessment.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111570DOI Listing
January 2021

Therapeutic inhibition of miR-802 protects against obesity through AMPK-mediated regulation of hepatic lipid metabolism.

Theranostics 2021 1;11(3):1079-1099. Epub 2021 Jan 1.

Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Center for global health, Nanjing Medical University, Nanjing, Jiangsu, China.

The host-parasite relationship is based on subtle interplay between parasite survival strategies and host defense mechanisms. It is well known that helminth infection, which afflicts more than one billion people globally, correlates with a decreased prevalence of obesity. Dissecting the underlying mechanisms can provide new targets for treating obesity from the host-parasite interaction perspective. C57BL/6 mice received a normal or high-fat diet (HFD) with or without Sjp40 (one main component of schistosome-derived soluble egg antigens) treatment. Both the loss and gain-of-function experiments by the inhibitor suppression and lentivirus treatment of miR-802 were utilized to elucidate the role of miR-802/AMPK axis in host lipid metabolism. Hepatocyte lipogenesis assay and metabolic parameters were assessed both and . The potential interactions among Sjp40, CD36, miR-802, Prkab1, and AMPK were clarified by pull-down, miRNA expression microarray, quantitative RT-PCR, dual-luciferase reporter assay, and western blotting analysis. We showed a link between decreased miR-802 and impaired lipid metabolism in infected mice. The decreased miR-802 promotes murine or human expression, respectively, which increases levels of phosphorylated AMPK, resulting in a decrease in hepatic lipogenesis. Also, injection with schistosome-derived soluble egg antigens (SEA) attenuated metabolism. We demonstrated that Sjp40 as a main component of SEA interacted with CD36 on hepatocytes to inhibit miR-802, resulting in the activation of AMPK pathway and subsequent attenuation of lipogenesis. Our study reveals the significant role of miR-802/AMPK axis in hepatic lipid metabolism and identifies the therapeutic potential of Sjp40 in treating obesity-related fatty liver.
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http://dx.doi.org/10.7150/thno.49354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738900PMC
July 2021

CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase.

FASEB J 2021 01;35(1):e21205

Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. We report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. Eggs recovered from livers of experimentally infected mice were transfected by electroporation with a CRISPR/Cas9-vector encoding gRNA X5 or X7 combining with/ without a ssODN donor. Next generation sequencing analysis of reads of amplicon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, an significantly enhanced Th2 response involving IL-4, -5, -10, and-13 was detected in lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, -13, and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes.
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http://dx.doi.org/10.1096/fj.202001745RRDOI Listing
January 2021

Effects of short-term upper limb robot-assisted therapy on the rehabilitation of sub-acute stroke patients.

Technol Health Care 2021 ;29(2):295-303

Background: Robot-assisted therapy (RT) has become a promising stroke rehabilitation intervention.

Objective: To examine the effects of short-term upper limb RT on the rehabilitation of sub-acute stroke patients.

Methods: Subjects were randomly assigned to the RT group (n= 23) or conventional rehabilitation (CR) group (n= 22). All subjects received conventional rehabilitation therapy for 30 minutes twice a day, for 2 weeks. In addition, the RT group received RT for 30 minutes twice a day, for 2 weeks. The outcomes before treatment (T0) and at 2 weeks (T1) and 1 month follow-up (T2) were evaluated in the patients using the upper limb motor function test of the Fugl-Meyer assessment (FMA) the Motricity Index (MI), the Modified Ashworth Scale (MAS), the Functional Independence Measure (FIM), and the Barthel Index (BI).

Results: There were significant improvements in motor function scales (P< 0.001 for FMA and MI) and activities of daily living (P< 0.001 for FIM and BI) but without muscle tone (MAS, P> 0.05) in the RT and CR groups. Compared to the CR group, the RT group showed improvements in motor function and activities of daily living (P< 0.05 for FMA, MI, FIM, BI) at T1 and T2. There was no significant difference between the two groups in muscle tone (MAS, P> 0.05).

Conclusions: RT may be a useful tool for sub-acute stroke patients' rehabilitation.
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http://dx.doi.org/10.3233/THC-202127DOI Listing
September 2021

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

Integrated remediation for organic-contaminated site by forcing running-water to modify alkali-heat/persulfate via oxidation process transfer.

Chemosphere 2021 Jan 16;262:128352. Epub 2020 Sep 16.

State Key Laboratory of Urban Water Resources and Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

As organic pollution of soil and groundwater increases, the effective and economical remediation of contaminated sites has drawn growing attention. In this study, running-water (RW) was designed to modify alkali-heat/persulfate (MAH/PS) for integrated remediation of an actual organic-contaminated site. The degradation efficiency mainly reached 60%-99% for Benz[a]anthracene, Benzo[a]pyrene and total petroleum hydrocarbons (TPHs). MAH/PS was more effective in degrading Benzene and 1,2-Dichloroethane with simple molecular configurations. The pollutant degradation efficiencies decreased with increasing site depth and increased with increasing pollutant concentrations. Migration with RW enhanced site remediation. By monitoring the groundwater after remediation, it was found that residual TPHs presented anomalous diffusion; SO ranged from 8.00 to 237.00 mg L to 8.00-290.00 mg L and pH presented alkalescence (7.00-8.20). Mathematical models were established to describe the reaction process including the solubility equilibrium of calcium hydroxide, temperature equilibrium, and reaction kinetics. Moreover, MAH/PS provided a cost-saving approach for site remediation.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128352DOI Listing
January 2021

CRISPR/Cas9: A new tool for the study and control of helminth parasites.

Bioessays 2021 01 4;43(1):e2000185. Epub 2020 Nov 4.

Immunology Department, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.

Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9-targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9-mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration.
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http://dx.doi.org/10.1002/bies.202000185DOI Listing
January 2021

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource.

Gut 2021 Apr 1;70(4):677-686. Epub 2020 Oct 1.

Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn's disease (CD), including their impact on need for surgery.

Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines.

Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015).

Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD.
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http://dx.doi.org/10.1136/gutjnl-2019-320185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948184PMC
April 2021

Effects of visual feedback balance training with the Pro-kin system on walking and self-care abilities in stroke patients.

Medicine (Baltimore) 2020 Sep;99(39):e22425

Sino-French Department of Neurological Rehabilitation, Gansu Provincial Hospital, Lanzhou, Gansu, China.

Some scholars' studies have demonstrated that Pro-kin balance system training is able to promote the recovery of the balance function in stroke patients. The present study has expanded on those studies, and was not merely limited to studying balance, but also encompassed walking and self-care abilities of the patients; furthermore, the association among balance and walking and self-care abilities was also explored.A total of 40 stroke patients were randomly and equally divided into 2 groups: the control group (n = 20) and the treatment group (n = 20). Both groups underwent conventional balance training, although the treatment group also underwent visual feedback balance training with the Pro-kin system. The balance function was assessed using the Berg Balance Scale (BBS), the Timed "Up & Go" (TUG) test, and Pro-kin system parameters. The Pro-kin system parameters included the perimeter and ellipse area, which were both tested once with eyes open (EO) and eyes closed (EC). Walking ability was assessed using the Holden Walking Ability Scale, according to the Functional Ambulation Classification (FAC). The self-care abilities were assessed with the Barthel Index (BI). The tests were conducted prior to training, and 3 weeks after the end of the training programme.No significant differences were noted among the groups before the training. After 3 weeks of training, for both the groups, significant improvements in balance and the walking and self-care abilities were noted: The BBS value was significantly increased (P < .05), whereas the TUG, perimeter, and ellipse area with EO and EC measurements were significantly decreased after treatment (P < .05). The FAC and BI readings were significantly increased after treatment (P < 0.05), and the treatment group outperformed the control group (P < .05). Furthermore, the balance function was shown to be strongly correlated with the walking and self-care abilities (P < .01).The present study has demonstrated that the use of the Pro-kin visual feedback balance training system in combination with conventional training is a viable method for improving walking and self-care abilities of stroke patients.
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http://dx.doi.org/10.1097/MD.0000000000022425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523840PMC
September 2020

A comparative proteomics analysis of the egg secretions of three major schistosome species.

Mol Biochem Parasitol 2020 11 19;240:111322. Epub 2020 Sep 19.

School of Biological Sciences, Queen's University Belfast, Belfast, United Kingdom. Electronic address:

Morbidity associated with hepatic and urogenital schistosomiasis stems primarily from the host immune response directed against schistosome eggs. When eggs become entrapped in host tissues, the development of fibrotic plaques drives downstream pathology. These events occur due to the antigenic nature of egg excretory/secretory products (ESPs). Both Schistosoma mansoni and S. japonicum ESPs have been shown to interact with several cell populations in the host liver including hepatocytes, macrophages, and hepatic stellate cells, with both immunomodulatory and pathological consequences. Several protein components of the ESPs of S. mansoni and S. japonicum eggs have been characterised; however, studies into the collective contents of schistosome egg ESPs are lacking. Utilising shotgun mass spectrometry and an array of in silico analyses, we identified 266, 90 and 50 proteins within the S. mansoni, S. japonicum and S. haematobium egg secretomes respectively. We identified numerous proteins with already established immunomodulatory activities, vaccine candidates and vesicle markers. Relatively few common orthologues within the ESPs were identified by BLAST, indicating that the three egg secretomes differ in content significantly. Having a clearer understanding of these components may lead to the identification of new proteins with uncharacterised immunomodulatory potential or pathological relevance. This will enhance our understanding of host-parasite interactions, particularly those occurring during chronic schistosomiasis, and pave the way towards novel therapeutics and vaccines.
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http://dx.doi.org/10.1016/j.molbiopara.2020.111322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059868PMC
November 2020
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