Validation of the revised electronic version of RUCAM for diagnosis of DILI in Chinese patients.

BACKGROUND AIMS: The Revised Electronic Causality Assessment Method (RECAM), a computerized update of the Roussel Uclaf Causality Assessment Methodology (RUCAM), was recently proposed. In this study, we validated and compared the utility of the RECAM and RUCAM in Chinese patients with a single conventional or herbal agent-induced liver injury. METHODS: In this retrospective multicenter cohort of well-established DILI and non-DILI patients from 5 centers in China, the diagnostic performance of the RUCAM and RECAM was compared by AUC analysis. The consistency was evaluated by weighted kappa. The major causes of discrepancy were explored. RESULTS: A total of 481 DILI and 100 non-DILI patients were included. In total, 62.6% of the DILI cases were induced by conventional agents, and 37.4% were induced by herbs. The RECAM had relatively higher AUC than RUCAM for overall [0.947 (0.926-0.964) vs. 0.867 (0.836-0.893), p=0.0016], conventional agents [0.923 (0.890-0.949) vs. 0.819 (0.775-0.858), p=0.0185], and herbs [0.972 (0.941-0.989) vs.0.911 (0.866-0.944), p=0.0199]. Latency, scores associated with hepatitis B, and hepatotoxicity information of the insulting drugs were the 3 main causes for the inconsistency between RECAM and RUCAM scores. CONCLUSIONS: The RECAM had relatively better diagnostic performance than RUCAM, with a higher AUC for Chinese DILI patients. Timely updates of the LiverTox category and refinement of serum markers to exclude hepatitis B activity would further improve the applicability of RECAM in areas where the use of herbs and resolution of past HBV infections are common.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.

Near-infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070-nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the ß-amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm-2 1070-nm light at a 10-Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti-inflammatory type. This induces secretion of M2 microglial-derived exosomes containing miR-7670-3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR-7670-3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070-nm light-modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near-infrared photobiomodulation.

Analysis on key parameters in subretinal injection facilitating a predictable and automated robot-assisted treatment in gene therapy.

BACKGROUND: Subretinal injection (SRI) has become an important surgical method for treating vitreoretinal diseases. Nevertheless, the optimisation of bleb formation in SRI, for the attainment of desired therapeutic outcomes, still requires further investigation. METHODS: This study analysed the influence of surgical parameters on SRI using a robotic setup. The surgical procedure was automated using visual guidance. A predictive model for bleb formation was established through regression analysis. To validate the model, we compared the clinical data's target area with the simulated SRI's actual area using parameters determined by the predictive model. RESULTS: The insertion angle dominated the eccentricity and area of the bleb. The injection speed dominated the axial angle. Automated SRI increased success rate and produced predictable outcomes. CONCLUSIONS: We could provide accurate SRI on phantom models by adjusting surgical parameters based on the patient's clinical information. Automatic robot-assisted SRI is a promising surgical technique with highly predictable results.

A metabarcoding protocol targeting two DNA regions to analyze root-associated fungal communities in ferns and lycophytes.

Premise: Detailed studies of the fungi associated with lycophytes and ferns provide crucial insights into the early evolution of land plants. However, most investigations to date have assessed fern-fungus interactions based only on visual root inspection. In the present research, we establish and evaluate a metabarcoding protocol to analyze the fungal communities associated with fern and lycophyte roots. Methods: We used two primer pairs focused on the ITS rRNA region to screen the general fungal communities, and the 18S rRNA to target Glomeromycota fungi (i.e., arbuscular mycorrhizal fungi). To test these approaches, we collected and processed roots from 12 phylogenetically distant fern and lycophyte species. Results: We found marked compositional differences between the ITS and 18S data sets. While the ITS data set demonstrated the dominance of orders Glomerales (phylum Glomeromycota), Pleosporales, and Helotiales (both in phylum Ascomycota), the 18S data set revealed the greatest diversity of Glomeromycota. Non-metric multidimensional scaling (NMDS) ordination suggested an important geographical effect in sample similarities. Discussion: The ITS-based approach is a reliable and effective method to analyze the fungal communities associated with fern and lycophyte roots. The 18S approach is more appropriate for studies focused on the detailed screening of arbuscular mycorrhizal fungi.

Premisa: El estudio de los hongos asociados a licofitas y helechos proporciona información crucial sobre la evolución temprana de las plantas terrestres. Sin embargo, hasta el momento, la mayoría de las investigaciones ha evaluado las interacciones helecho­hongo basándose solamente en la observación directa de las raíces. En la presente investigación, establecemos y evaluamos un protocolo de metabarcoding enfocado en dos regiones de ADN para analizar las comunidades fúngicas asociadas a las raíces de helechos y licofitas. Métodos: Utilizamos dos pares de primer orientados hacia la región ITS ARNr, para la detección de las comunidades fúngicas generales, y la región 18S ARNr, para captar hongos pertenecientes al phylum Glomeromycota (i.e., hongos micorrícicos arbusculares). Para evaluar estos procedimientos, nosotros recolectamos y procesamos raíces de 12 especies de helechos y licofitas distantes desde el punto de vista filogenético. Resultados: Se observaron claras diferencias de composición entre los sets de datos ITS y 18S: mientras el primero demostró un predominio de los órdenes Glomerales (phylum Glomeromycota), Pleosporales y Helotiales (ambos en phylum Ascomycota), el set 18S reveló la mayor diversidad de hongos micorrizógenos arbusculares. Ninguno de los marcadores moleculares utilizados detectó miembros del phylum Mucoromycota en las muestras. El escalamiento multidimensional no métrico (NMDS) sugirió un papel importante de la región geográfica de origen en la determinación de las similitudes entre muestras. Discusión: El método basado en la región ITS es consistente, replicable y eficaz para analizar las comunidades fúngicas asociadas con raíces de helechos y licofitos. El enfoque 18S es más apropiado para estudios centrados en la detección de los hongos micorrizógenos arbusculares.

Recovery of Li2CO3 from Spent LiFePO4 by Using a Novel Impurity Elimination Process.

The large-scale implementations of lithium iron phosphate (LFP) batteries for energy storage systems have been gaining attention around the world due to their quality of high technological maturity and flexible configuration. Unfortunately, the exponential production of LFP batteries is accompanied by an annual accumulation of spent batteries and a premature consumption of the lithium resource. Recycling souring critical battery materials such as Li2CO3 is essential to reduce the supply chain risk and achieve net carbon neutrality goals. During the recovery of Li2CO3, impurity removal is the most crucial step in the hydrometallurgy process of spent LiFePO4, which determines the purity of Li2CO3. By investigating and comparing the results of impurity elimination from the purified Li+-containing liquids with strong and weak alkalis under identical pH conditions, respectively, a strategy based on an alkali mixture has been proposed. The purified Li+-containing liquid was, thereafter, concentrated and sodium carbonate was added in order to precipitate Li2CO3. As a result, a high purity Li2CO3 (99.51%) of battery grade was obtained. LiFePO4 prepared with the recovered Li2CO3 and FePO4 as raw materials also displayed a comparative high capacity and stable cycle performance to the commercial product and further verified the electrochemical activity of the recovered materials.

Langbiangia, a new genus of Gesneriaceae endemic to Langbiang Plateau, southern Vietnam and a taxonomic endeavor to achieve key targets of the post-2020 global biodiversity framework.

Situated in the southern end of the Annamite Mountain Range, Langbiang Plateau is a major biodiversity hotspot of southern Vietnam known for high species diversity and endemicity. To achieve effective conservation, parts of the plateau were designated as the Langbiang Biosphere Reserve, an UNESCO World Network aiming to improve relationships between inhabitants and their environments. Amongst the rich endemic flora of the plateau are three gesneriads ascribed to Primulina, a calciphilous genus with high species diversity in the vast limestone karsts stretching from southern China to northern Vietnam. However, a recent phylogenetic study questioned the generic placement of the Langbiang Primulina, corroborating with observations on the geographical distribution, habitat preference, and phyllotaxy of the three species. Based on phylogenetic analyses of nuclear ITS and plastid trnL-F DNA sequences of a comprehensive sampling covering nearly all genera of the Old World Gesneriaceae, we demonstrate that the three Langbiang Primulina species form a fully supported clade distantly related to other Primulina. As this clade is biogeographically, ecologically, morphologically, and phylogenetically distinct worthy of generic recognition, we propose to name it Langbiangia gen. nov. to highlight the rich and unique biodiversity of the Langbiang Plateau. By means of this taxonomic endeavor, we are hoping to raise the conservation awareness of this biodiversity heritage of southern Vietnam and promote the importance of Langbiang Biosphere Reserve that is crucial for achieving action-oriented global targets of the post-2020 global biodiversity framework (GBF) of the UN Convention on Biological Diversity (CBD)-effective conservation and management of at least 30% of biodiverse terrestrial, inland water, and costal and marine areas by 2030-that has been agreed at the COP15 in Montréal in December 2022.

Systematics and biogeography of the Old World fern genus Antrophyum.

Antrophyum is one of the largest genera of vittarioid ferns (Pteridaceae) and is most diverse in tropical Asia and the Pacific Islands, but also occurs in temperate Asia, Australia, tropical Africa and the Malagasy region. The only monographic study of Antrophyum was published more than a century ago and a modern assessment of its diversity is lacking. Here, we reconstructed a comprehensively sampled and robustly supported phylogeny for the genus based on four chloroplast markers using Bayesian inference, maximum likelihood and maximum parsimony analyses. We then explored the evolution of the genus from the perspectives of morphology, systematics and historical biogeography. We investigated nine critical morphological characters using a morphometric approach and reconstructed their evolution on the phylogeny. We describe four new species and provide new insight into species delimitation. We currently recognize 34 species for the genus and provide a key to identify them. The results of biogeographical analysis suggest that the distribution of extant species is largely shaped by both ancient and recent dispersal events.

Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial.

BACKGROUND & AIMS: Hepatitis B virus infection frequently leads to liver fibrosis and is the leading cause of hepatocellular carcinoma and cirrhosis in Asia Pacific. Pirfenidone is approved by the United States Food and Drug Administration for treatment of idiopathic pulmonary fibrosis, and hydronidone is a novel structural modification of pirfenidone with the aim of reducing hepatoxicity. We aimed to investigate the safety and efficacy of hydronidone in patients with chronic hepatitis B (CHB)-associated liver fibrosis. METHODS: This was a 52-week multicenter, randomized, double-blind, placebo-controlled, phase II study at 8 centers in China. Patients with CHB with biopsied documented liver fibrosis were eligible and were randomly assigned into receiving daily placebo or hydronidone orally (180 mg/day, 270 mg/day, or 360 mg/day). All enrolled subjects also received entecavir 0.5 mg/day. A second liver biopsy was performed at week 52. The primary endpoint was defined as fibrosis improvement (reduction of at least 1 Ishak score at week 52 of treatment). RESULTS: From June 25, 2015, to September 5, 2019, 168 patients with CHB and liver fibrosis met the inclusion/exclusion criteria and were subsequently randomized, 43 in the placebo group and 125 in the hydronidone groups (42 in the 180-mg group, 42 in the 270-mg group, and 41 in the 360-mg group). The fibrosis improvement endpoint was achieved by 11 patients (25.6%) in the placebo group and 17 patients (40.5%) in the 180-mg group (P = .12), 23 patients (54.8%) in the 270-mg group (P = .006), and 18 patients (43.90%) in the 360-mg group (P = .08). The improvement rate was 58 of 125 (46.4%) in the combined hydronidone group (P = .014). The overall safety profile and incidence of serious adverse events were similar among the groups. CONCLUSIONS: Hydronidone plus entecavir showed clinically significant histological improvement of liver fibrosis in patients with CHB, and the dose of 270 mg showed the best efficacy of fibrosis regression. Further studies are required to assess the long-term effectiveness of hydronidone in regression of hepatic fibrosis. CLINICALTRIALS: gov number, NCT02499562.

Morphological study of CT image of posterior pilon variant fracture and its possible clinical significance.

OBJECTIVE: The incidence of posterior pilon variant fractures has been underestimated. The purpose was to study the characteristics of posteromedial (PM) and posterolateral (PL) fragments in CT imaging of posterior pilon variant fractures, and to provide help for clinical diagnosis and treatment. METHODS: CT imaging data of 109 cases of posterior pilon variant fractures in our hospital from January 2013 to December 2020 were retrospectively analyzed. According to Mason and Molloy classification, PM fragments were further divided into pilon subtypes and avulsed subtypes. The largest actual area of fragments in axial and sagittal were selected as the study plane, and the maximum axial lengths of X, Y and Z, α angle, ß angle, fragment area (S1-7) and fragment area ratio (FAR1-4), interfragmentary (IF) angle, and back of tibia (BT) angle were measured. RESULTS: A total of 109 cases were included in this study, 61 of whom were pilon subtypes [90.16% were supination-external rotation (SER) injuries]. 48 cases were avulsed subtypes [81.25% were pronation-external rotation (PER) injuries]. Pilon subtypes were larger than avulsed subtypes in X, Y, Z, α2 Angle, ß2 Angle, fragment area and ratio, and IF and BT angle (P < 0.05). There was no difference between α1 and ß1 angle (P > 0.05). CONCLUSION: The morphology of pilon subtype was larger than that of avulsion subtype. According to fragment size, morphology, and injury mechanism, two fragments of pilon subtype should be anatomic reduction and fixation. However, the PL fragment of avulsion subtype should to be fixed, while PM fragment may only need conservative treatment.

Systematics and Plastome Evolution in Schizaeaceae.

While the family Schizaeaceae (Schizaeales) represents only about 0.4% of the extant fern species diversity, it differs from other ferns greatly in gross morphologies, niche preferences, and life histories. One of the most notable features in this family is its mycoheterotrophic life style in the gametophytic stage, which appears to be associated with extensive losses of plastid genes. However, the limited number of sequenced plastomes, and the lack of a well-resolved phylogenetic framework of Schizaeaceae, makes it difficult to gain any further insight. Here, with a comprehensive sampling of ~77% of the species diversity of this family, we first inferred a plastid phylogeny of Schizaeaceae using three DNA regions. To resolve the deep relationships within this family, we then reconstructed a plastome-based phylogeny focusing on a selection of representatives that covered all the major clades. From this phylogenomic backbone, we traced the evolutionary histories of plastid genes and examined whether gene losses were associated with the evolution of gametophytic mycoheterotrophy. Our results reveal that extant Schizaeaceae is comprised of four major clades-Microschizaea, Actinostachys, Schizaea, and Schizaea pusilla. The loss of all plastid NADH-like dehydrogenase (ndh) genes was confirmed to have occurred in the ancestor of extant Schizaeaceae, which coincides with the evolution of mycoheterotrophy in this family. For chlorophyll biosynthesis genes (chl), the losses were interpreted as convergent in Schizaeaceae, and found not only in Actinostachys, a clade producing achlorophyllous gametophytes, but also in S. pusilla with chlorophyllous gametophytes. In addition, we discovered a previously undescribed but phylogenetically distinct species hidden in the Schizaea dichotoma complex and provided a taxonomic treatment and morphological diagnostics for this new species-Schizaea medusa. Finally, our phylogenetic results suggest that the current PPG I circumscription of Schizaea is non-monophyletic, and we therefore proposed a three-genus classification moving a subset of Schizaea species sensu PPG I to a third genus-Microschizaea.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial.

BACKGROUND AND AIMS: Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI. METHODS: This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial. Patients with idiosyncratic acute DILI were randomized 1: 1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID) and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment for 4 weeks. RESULTS: Overall, 241 patients were included in the full analysis set, with 81, 82 and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2 U/L in the low-dose bicyclol, high-dose bicyclol and control groups, respectively; both p < .001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6 and 8 were higher in the bicyclol-dependent groups than in the control group (p = .002 at week 1 and all p < .001 at weeks 2, 4, 6 and 8 respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol and control groups were 29, 16 and 43 days respectively. Adverse events, serious adverse events and adverse drug reactions were similar across groups. CONCLUSIONS: Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy. TRIAL REGISTRATION NUMBER: www. CLINICALTRIALS: gov (registration no. NCT02944552).

Zero-fluoroscopy ablation of left-sided arrhythmia substrates in children - Mid-term safety and feasibility study from transaortic approach.

BACKGROUND: A widely used method of treating left-sided arrhythmia substrates in children is retrograde transaortic ablation under fluoroscopic guidance. However, the feasibility, safety, and efficacy of this approach under zero fluoroscopy (ZF) guidance, especially the mid-term safety of anatomy and function of aortic valves, have yet to be proven. METHODS: All consecutive patients who received ablation of left-sided arrhythmias between January 2012 and June 2020 and below 20 years-old were enrolled. The study group submitted to 55 ZF-guided procedures using cardiac mapping system (EnSite Precision), whereas 49 procedures were performed under fluoroscopic guidance in the control group. Echocardiographic studies took place before and 6-months after ablative procedures. RESULTS: One-hundred-and-two patients (male, 66; female, 36) underwent a total of 104 ablative procedures. Mean procedural durations were 83.9 ± 44.4 min in the study group and 64.8 ± 29.1 min in the control group, respectively (p = .01; the 95% confidence interval, -33.57 to -4.63). Corresponding fluoroscopic times were .5 ± 2.2 min and 24.7 ± 13.9 min (p < .001; the 95% confidence interval, 20.15 to 28.22). ZF may be reasonably applied after a learning curve of 20 cases. Immediate procedural success and recurrence rates were similar in each groups. There was no detectable progression of aortic regurgitation in any of the patients during serial follow-up of echocardiography. CONCLUSION: ZF-guided retrograde transaortic ablation of left-sided arrhythmia substrates proved safe in children at midterm follow-up, reducing radiation exposure significantly within a learning curve of <20 cases.

Synoviolin inhibits the inflammatory cytokine secretion of Müller cells by reducing NLRP3.

The pro-inflammatory cytokines secreted by Müller cells aggregate retinal cell loss and vascularization in diabetic retinopathy (DR). The deubiquitinase BRCA1-BRCA2-containing complex subunit 3 (BRCC3)-mediated nucleotide-binding domain and leucine-rich repeat receptor containing a pyrin domain 3 (NLRP3) inflammasome activation participate in this progress. This study aims to clarify whether the E3 ubiquitin ligase synoviolin (SYVN1) relieves DR via regulating the BRCC3/NLRP3 axis. The DR model was established using streptozotocin-induced mice. Immunofluorescence staining with anti-CD31, anti-glutamine synthetase, and anti-vimentin was performed to identify DR and Müller cells. Levels of pro-inflammatory cytokines, including interleukin-1ß, tumor necrosis factor-α, IL-6, and IL-18, in murine serum and Müller cell supernatants were determined. Co-immunoprecipitation (Co-IP) and ubiquitination assays were used to clarify the interactions among SYVN1, BRCC3, and NLRP3. SYVN1 was reduced and BRCC3 was increased in DR retina and high glucose (HG)-induced Müller cells. Overexpressing 1 promoted the ubiquitination and degradation of BRCC3 and reduced the secretion of proinflammatory cytokines in HG-induced Müller cells. The simultaneous overexpression of 1 and Brcc3 restored the reduction of pro-inflammatory cytokines caused by the overexpression of 1 alone. Co-IP experiments confirmed the interaction between BRCC3 and NLRP3. SYVN1-mediated BRCC3 downregulation promoted NLRP3 ubiquitination and reduced pro-inflammatory cytokine secretion. 1 overexpression reduced retinal vascularization and inflammatory cytokine secretion in DR mice. SYVN1 has a protective effect on DR, whose molecular mechanisms are partly through SYVN1-mediated ubiquitination of BRCC3 and the subsequent downregulation of NLRP3.

LncRNA XIST restrains the activation of Müller cells and inflammation in diabetic retinopathy via stabilizing SIRT1.

BACKGROUND: Recent studies have provided strong evidence that lncRNAs play a functional regulatory role in diabetic retinopathy (DR). The purpose of this study was to investigate the effect of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) in DR. METHODS: A DR mouse model was established by intraperitoneal injection of streptozotocin (STZ), and then the mouse retinal Müller cells (mMCs) were isolated from retina tissues of mice. Human retinal Müller cell line (HMCs) and mMCs and were treated with high glucose (HG) to simulate an in vitro DR model. XIST expression was detected by qRT-PCR. Next, XIST overexpression was performed in mMCs and HMCs to examine its effect on the activation of Müller cells and production of pro-inflammatory cytokines. Subsequently, the interaction between XIST and SIRT1 was verified, and the ubiquitination level of SIRT1 as well as the stability of SIRT1 protein were assessed. RESULTS: XIST was down-regulated in retinal tissues of DR mice and HG-induced HMCs. Overexpression of XIST inhibited HG-induced activation of mMCs and HMCs, and reduced the production of pro-inflammatory cytokines. XIST promoted SIRT1 expression via interacting with SIRT1 and inhibiting the ubiquitination of SIRT1. Furthermore, SIRT1 silencing partly abrogated the effect of XIST overexpression on the activation of mMCs and HMCs as well as the production of pro-inflammatory cytokines induced by HG. CONCLUSION: We concluded that XIST restrained the activation of Müller cells and the production of pro-inflammatory cytokines via stabilizing SIRT1.

3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China.

BACKGROUND AND AIMS: Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236). METHODS: Chinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis. RESULTS: Of the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log10 IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (-0.4 vs. -3.2 mL/min; p=0.014) and less percentage change in bone mineral density vs. TDF at hip (-0.95% vs. -1.93%) and spine (+0.35% vs. -1.40%). CONCLUSIONS: In chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.

Bicyclol for the treatment of drug-induced liver injury: a propensity score matching analysis using a nationwide inpatient database.

OBJECTIVE: To evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database. METHODS: We retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified. RESULTS: The analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups. CONCLUSIONS: Bicyclol is a potential candidate for DILI.

Diagnostic Performance of FibroTouch Ultrasound Attenuation Parameter and Liver Stiffness Measurement in Assessing Hepatic Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.