Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study.

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

Biosynthesis and characterization of selenium nanoparticles from Andrographis alata: Assessment of their potential antimicrobial, antidiabetic, anti-Alzheimer's and wound healing properties.

Recently, there has been a lot of focus on the environmentally friendly, specifically plant-based, synthesis of nanoparticles. The extract of leaves from Andrographis alata (A. alata) was used in the current work as a reducing agent to create selenium nanoparticles (SeNPs), which will be used in biological applications (antibacterial, antioxidant and antidiabetic, anti-Alzheimer's and wound healing properties). As part of detailed characterization, the UV-Vis spectra showed an absorption peak at 274 nm with a size in the range of 55-75 nm were shown in morphological investigations using EDS, DLS and SEM analysis to have crystalline spherical-shaped structures. Against several harmful bacterial strains, SeNPs demonstrated a remarkable antibacterial effectiveness. The minimum inhibitory concentration (MIC) of synthesized SeNPs completely prevented the development of various pathogens. Furthermore, bio-reduced SeNPs showed high cholinesterase inhibition efficacy and good antipotential Alzheimer's. According to the current research, treatment with biosynthesized SeNPs stimulates faster wound healing in NIH3T3 murine fibroblast cell lines without cytotoxicity. Different in vitro biological experiments also showed that, when compared with the extract of A. alata, bio-reduced SeNPs had considerable antibacterial, antioxidant effects, antidiabetic, anti-Alzheimer's and wound healing. In general, the findings demonstrate the efficacy and prospective therapeutic uses of SeNPs.

Integrated strategy facilitates rapid in-depth chemome characterization of traditional Chinese medicine prescriptions: Shengbai oral liquid as a case.

Chemome characterization is the prerequisite for either therapeutic mechanism clarification or quality control of traditional Chinese medicine prescriptions (TCMPs). Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) currently serves as the most popular analytical tool; however, chemome characterization is still challenged by MS/MS spectral acquisition and post-acquisition data processing. Here, an integrated strategy was proposed for in-depth chemome clarification of Shengbai oral liquid (SBOL). Gas phase ion fractionation with staggered mass ranges was demonstrated to be the superior acquisition method regarding MS2 spectrum coverage in this study, and narrower mass range further advanced coverage. To facilitate information extraction, all ingredient materials were measured in parallel to form an in-house library, where each MS1 -MS2 item generated a square mass-to-charge ratio (m/z) frame to capture the tagged identity and each chemical family produced a pentagon frame for mass defect features to accomplish chemical analogs-targeted quasi-molecular ion extraction. Square m/z frame imprinting captured 355 identities, while mass defect frames extracted 275 compounds. Attributing to comprehensive MS2 spectrum acquisition and efficient data processing, 355 components were captured and tentatively identified, resulting in a clarified chemical composition for SBOL. Therefore, the proposed strategy should be meaningful for the chemome characterization of TCMPs.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Metal oxide modified biochars for fertile soil management: Effects on soil phosphorus transformation, enzyme activity, microbe community, and plant growth.

Metal oxide modified biochars are increasingly being used for intensive agricultural soil remediation, but there has been limited research on their effects on soil phosphorus transformation, soil enzyme activity, microbe community and plant growth. Two highly-performance metal oxides biochars (FeAl-biochar and MgAl-biochar) were investigated for their effects on soil phosphorus availability, fractions, enzyme activity, microbe community and plant growth in two typical intensive fertile agricultural soils. Adding raw biochar to acidic soil increased NH4Cl-P content, while metal oxide biochar reduced NH4Cl-P content by binding to phosphorus. Original biochar slightly reduced Al-P content in lateritic red soil, while metal oxide biochar increased it. LBC and FBC significantly reduced Ca2-P and Ca8-P properties while improving Al-P and Fe-P, respectively. Inorganic phosphorus-solubilizing bacteria increased in abundance with biochar amendment in both soil types, and biochar addition affected soil pH and phosphorus fractions, leading to changes in bacterial growth and community structure. Biochar's microporous structure allowed it to adsorb phosphorus and aluminum ions, making them more available for plants and reducing leaching. In calcareous soils, biochar additions may dominantly increase the Ca (hydro)oxides bounded P or soluble P instead of Fe-P or Al-P through biotic pathways, favoring plant growth. The recommendations for using metal oxides biochar for fertile soil management include using LBC biochar for optimal performance in both P leaching reduction and plant growth promotion, with the mechanisms differing depending on soil type. This research highlights the potential of metal oxide modified biochars for improving soil fertility and reducing phosphorus leaching, with specific recommendations for their use in different soil types.

Orally administered BZL-sRNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice.

The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.

Protein arginine N-methyltransferase 4 (PRMT4) contributes to lymphopenia in experimental sepsis.

BACKGROUND: One hallmark of sepsis is the reduced number of lymphocytes, termed lymphopenia, that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by their epigenetic and non-epigenetic functions; however, the role of these enzymes in lymphopenia remains elusive. METHODS: We used molecular biological approaches to investigate the high expression and function of a chromatin modulator protein arginine N-methyltransferase 4 (PRMT4)/coactivator-associated arginine methyltransferase 1 in human samples from septic patients and cellular and animal septic models. RESULTS: We identified that PRMT4 is elevated systemically in septic patients and experimental sepsis. Gram-negative bacteria and their derived endotoxin lipopolysaccharide (LPS) increased PRMT4 in B and T lymphocytes and THP-1 monocytes. Single-cell RNA sequencing results indicate an increase of PRMT4 gene expression in activated T lymphocytes. Augmented PRMT4 is crucial for inducing lymphocyte apoptosis but not monocyte THP-1 cells. Ectopic expression of PRMT4 protein caused substantial lymphocyte death via caspase 3-mediated cell death signalling, and knockout of PRMT4 abolished LPS-mediated lymphocyte death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. CONCLUSIONS: These findings demonstrate a previously uncharacterised role of a key chromatin modulator in lymphocyte survival that may shed light on devising therapeutic modalities to lessen the severity of septic immunosuppression.

A mechanistic review of chinese medicine polyphenols on bone formation and resorption.

Bone reconstruction includes a steady state system of bone formation and bone absorption. This tight coupling requires subtle coordination between osteoblasts and osteoclasts. If this balance is broken, it will lead to bone mass loss, bone density reduction, and bone metabolic diseases, such as osteoporosis. Polyphenols in Chinese herbal medicines are active ingredients in plant extracts with high safety and few side effects, and they can play a role in affecting bone formation and bone resorption. Some of these have estrogen-like effects and can better target bone health in postmenopausal women. The purpose of this review is to provide comprehensive information on the mechanisms underlying the relationship between traditional Chinese medicine polyphenols and bone formation or bone resorption.

Interception of fertile soil phosphorus leaching with immobilization materials: Recent progresses, opportunities and challenges.

The non-point source pollution induced by phosphorus (P) leaching from fertile soils is accelerating the eutrophication phenomena in aqueous ecosystems. Herein, to alleviate and intercept the P leaching from the fertile soils, diverse P immobilization materials (PIM) which can transform labile P into stable P via a range of physicochemical and biological interactions have been adopted and received increasing research interest. However, the remediation mechanisms of different PIMs were complex and vary with soil properties and PIM application methods. In this review, the P fraction and mobility characteristics of different fertile soils were first introduced. Then, three kinds of PIM including inorganic materials (e.g., clay minerals and red mud), organic materials (e.g., polyacrylamide), and composites (e.g., modified biochar) applied in soil P leaching interception were concluded. The key factors (i.e., soil pH, soil texture, organic matter content and variable soil moisture) influencing PIM performance and potential PIMs used for reducing soil P leaching were also introduced. Current review can favor for proposing more suitable and insightful strategies to regulate the fertile soil P and achieve the dual goals of improving the crop land quality and yield, and preventing agricultural non-point source pollution.

High-salt diet accelerates bone loss accompanied by activation of ion channels related to kidney and bone tissue in ovariectomized rats.

Excessive salt intake can induce a variety of diseases, such as hypertension, cardiovascular disease, kidney disease and so on，it is also one of the factors promoting bone resorption. The mechanism of osteoporosis-induced exacerbations of high salt diet is not well-defined. In this study, we used ovariectomized 6-month-old Sprague Dawley rats to construct a high bone turnover model, and then administrated with high sodium chloride diet (2.0% w/w NaCl, 8.0% w/w NaCl) for 12 weeks to observe the effect of high salt diet on bone metabolism. The results showed that high salt diet could lead to the destruction of bone microstructure, promote the excretion of urinary calcium and phosphorus and accelerate the bone turnover, as well as cause the pathologic structural abnormalities in renal tubular. At the same time, it was accompanied by the up-regulated expression of the epithelial sodium channel (ENaCα), voltage-gated chloride channels (ClC)- 3 and the down-regulated expression of Na-Cl cotransporter (NCC), sodium calcium exchanger (NCX1) in femoral tissue and renal tubules. These findings confirm that high salt diet can destroy the microstructure of bone by increasing bone resorption and affect some ion channels of bone tissue and renal tubule in ovariectomized rats.

Identifying biotic and abiotic processes of reversing biochar-induced soil phosphorus leaching through biochar modification with MgAl layered (hydr)oxides.

Biochar (BC) as a increasing widely adopted soil amendments showed potential threat to soil P leaching, but the relevant mechanisms were not clear enough and relevant strategy should be proposed to address the P leaching induced by BC application. In this study, effects of ordinary corn straw BC, and a fabricated Mg/Al-LDHs modified biochar (LBC) on soil P availability, adsorption, fraction and mobility were compared and investigated by conducting the column and incubation experiments at biochar to soil rate of 1 %, 2 % and 4 % (w/w). Chemical sequential extraction methods and various solid-state method (i.e., three-dimensional excitation emission matrix (EEM), x-ray diffraction (XRD), scanning electron micrograph (SEM) and P K-edge X-ray absorption near edge structure (XANES)) were utilized to give deep insights into the P mobilization and immobilization mechanisms by respectively applying the BC and LBC. Results of incubation experiments showed that applying the LBC reduced the labile P with significant CaP transformation to Al-retained P, while ordinary BC promoted the Fe/Al-P transformation to labile dibasic calcium phosphate and monobasic calcium phosphate evidenced by the EEM analysis, in-situ XANES investigation and chemical sequential extraction methods. Results of phosphatase and microbial analyses indicated that the decreased labile P after 30 days' incubation and the mitigated P leaching in LBC treatment were dominantly ascribed to abiotic processes of inorganic P transformation and (de)sorption. This research gave deep insights into abiotic and biotic processes of ordinary biochar promoting soil P leaching, and important implications for applying engineered biochar in reducing P leaching and improving soil productivity.

Incidence and risk factors of drug-induced liver injury.

The epidemiology and aetiology of drug-induced liver injury (DILI) vary across different countries and populations. Overall, DILI is rare in the general population but has become more prevalent in hospitalized patients, especially among patients with unexplained liver conditions. In addition, drugs implicated in DILI differ between Western and Eastern countries. Antibiotics are the leading drugs implicated in DILI in the West, whereas traditional Chinese medicine is the primary cause implicated in DILI in the East. The incidence of herbal and dietary supplements-induced hepatotoxicity is increasing globally. Several genetic and nongenetic risk factors associated with DILI have been described in the literature; however, there are no confirmed risk factors for all-cause DILI. Some factors may contribute to the risk of DILI in a drug-specific manner.

Glycine Acts Through Estrogen Receptor Alpha to Mediate Estrogen Receptor Signaling, Stimulating Osteogenesis and Attenuating Adipogenesis in Ovariectomized Rats.

SCOPE: Glycine is commonly used as an additive in bone health supplements, the activity and differentiation of bone mesenchymal stem cells (BMSCs) are essential to bone metabolism, but the effect of Glycine on bone metabolism and specific mechanism are not fully clarified. METHODS AND RESULTS: The ovariectomized rats to evaluate the effects of Glycine on bone quality and quantity is constructed; then used an ER signaling inhibitor (ICI182780) and an ERα deficient BMSCs to explore how Glycine mediated ERα regulating the osteogenic and adipogenic differentiation of BMSCs; furthermore, an autodock analysis is used to assess the affinity of Glycine and ERα. The results show that Glycine significantly moderated bone mass and bone microstructure in ovariectomized rats; Glycine stimulates the osteogenic differentiation and attenuates the adipogenic differentiation in OVX rats and BMSCs, and these effects could be abolished by ICI 182780; further docking experiment showes that Glycine and ERα have a stronger affinity, and finally proves that the impact of Glycine could be blocked by ERα. CONCLUSION: Glycine stimulates osteogenesis and attenuates adipogenesis in ovariectomized rats, which process may involve in ERα mediated ER signaling pathway.

Acceptability of Vegetable Fortified Ugali in Sub-Saharan Africa.

Corn flour-based porridge like dough, ugali, is the staple food of low-income population in sub-Saharan Africa. Lack of vitamin A, carotenoids, and dietary fibers brings about serious health issues to this population. In this study, vegetables including bok choy, broccoli, cabbage, carrot, Chinese onion stalk (C_onion), mushroom, are added during the cooking of ugali, as nutritional supplements. The freeze-dried powder of each vegetable was used for its long storage, stable nutrients, and similar particle size. Sub-Saharan African assessors were trained and sensory evaluated the six different vegetable fortified ugali with the plain, unfortified as the control on five attributes. The plain ugali was indistinguishable with the C_onion stalk fortified in color, with the carrot and C_onion stalk fortified in odor, with all vegetables (except broccoli and mushroom) fortified ugali in taste, with carrot and C_onion stalk fortified in granularity, and with cabbage, carrot, C_onion stalk fortified in viscosity. Preference ranking analysis showed that the C_onion stalk fortified ugali is even more favorably preferred than the plain, unfortified ugali, probably due to the umami components in C_onion that serve as the taste enhancer. This study indicates that Chinese onion stalk is a potential vegetable supplement to population in the sub-Saharan Africa.

Smart MXene/agarose hydrogel with photothermal property for controlled drug release.

Smart hydrogels responsive to minimally invasive near-infrared (NIR) light have great potential in localized drug delivery for cancer treatment, but they still show some limitations such as low photothermal conversion, poor photothermal stability, and improper temperature range in biomedical applications. In this paper, the two-dimensional MXene nanosheets with high photothermal conversion efficiency as well as photothermal stability was firstly prepared, then the MXene nanosheets and the therapeutic drug were embedded in the low-melting-point agarose hydrogel network to fabricate the drug-loaded MXene/agarose hydrogel (MXene@Hydrogel). With the addition of low concentration of MXene (20 ppm), the MXene@Hydrogel could quickly rise to 60 °C under NIR irradiation and melt to release the encapsulated drugs. Importantly, the drug on/off release and the kinetics could be easily controlled with varied agarose concentration, MXene concentration, light intensity, and exposure time. In addition, the drug doxorubicin retained the anticancer activity after released from the MXene@Hydrogel network under NIR irradiation. With the excellent biocompatibility, the newly fabricated NIR-responsive MXene@Hydrogel offers a novel way for the development of smart hydrogel-based drug delivery system for localized cancer treatment.

Hugan tablets for the treatment of RUCAM based drug-induced liver injury: a propensity score matching analysis using a nationwide database.

BACKGROUND: Drug-induced liver injury (DILI) is a major clinical challenge with no specific therapeutic drugs available. It is crucial to develop new agents to improve the clinical outcome of patients with DILI. This study evaluated the efficacy and safety of Hugan tablets in DILI patients using a nationwide database. RESEARCH DESIGN AND METHODS: We analyzed the clinical data of DILI patients from a nationwide DILI database (www.hepatox.org). Patients who received oral Hugan tablets for DILI were defined as the Hugan group, and those who received no treatment for DILI were defined as the control group. RESULTS: There were 111 cases in the Hugan group and 512 cases in the control group. One-to-one propensity score matching created 111 matched pairs. The normalization rates of alanine aminotransferase and aspartate aminotransferase in the Hugan group were significantly higher than those in the control group (50.45% vs. 26.13%, p ≤ .0002 and 67.57% vs. 41.75%, p ≤ .0001). There were no differences in the incidence of renal function impairment or blood abnormality between the two groups. CONCLUSIONS: Hugan tablets are safe and effective in DILI treatment. Large-scale randomized controlled studies are needed to explore the effects of Hugan tablets on DILI induced by different offending drugs. TRIAL REGISTRATION: The study protocol was posted on ClinicalTrials.gov with NCT number: NCT02407964.

Single dose testosterone administration enhances novelty responsiveness and short-term habituation in healthy males.

The role of testosterone in sensory perception suggests that testosterone likely regulates adaptive responses to sensory changes, including habituation to repeated events and responsiveness to novel events. To test this hypothesis, we investigated how testosterone modulates brain responses to rapid changes in sensory inputs. Using a double-blind, placebo-controlled, within-participant design, each participant received a single dose of either testosterone or placebo, and then completed a passive auditory oddball task in which infrequent deviant tones were embedded in a series of frequent standard tones. Analysis of novelty-evoked potentials revealed smaller Mismatch Negativity (MMN) responses, but larger P3a responses in the testosterone session than in the placebo session. This suggests testosterone attenuates MMN responses that are associated with pre-attentive novelty detection and enhances P3a responses that are associated with involuntary attentional orientation toward novelty. Along with the repetition of standard tones, P2 responses on the auditory evoked potentials became significantly attenuated in the testosterone session, but not in the placebo session. This suggests testosterone enhances short-term habituation of P2 responses to recurring sensory events, which has been associated with bottom-up attention allocation. Mediation analysis further revealed that the role of testosterone in promoting attentional orientation toward novelty could be explained by the influence it exerts on short-term habituation and pre-attentive novelty detection. Overall, testosterone facilitated involuntary attention switching-withdrawal of attention from repeated sensory events and orientation toward novel sensory events-at the cost of attenuated pre-attentive novelty detection. This finding provides insight into the interplay between endocrinology and involuntary attentional processes.

Quercetin regulates ERα mediated differentiation of BMSCs through circular RNA.

Circular RNA (circRNA) participates in regulation of gene transcription, while estrogen receptor alpha (ERα) and quercetin (QUE) positively regulate bone formation, but little is known about the correlation among circRNA, ERα and QUE. In this experiment, we created an ERα-deficient rBMSC model treated with QUE and evaluated the effects of ERα or QUE on rBMSCs, then analyzed differentially-expressed circRNAs by RNA-Seq and bioinformatics. The results showed that ERα deficiency constrained osteogenic differentiation and stimulated adipocytic differentiation of rBMSCs, while QUE abrogated those effects. We identified 136 differentially-expressed circRNAs in the Lv-shERα group and 120 differentially-expressed circRNAs in the Lv-shERα + QUE group. Thirty-two circRNAs retroregulated by ERα and QUE were involved in Rap1 and Wnt signaling, and four of them together sponged miR-326-5p, the target genes of which are osteogenic and adipogenic differentiation factors. Further study showed that over-expressed miR-326-5p could stimulate osteogenic differentiation, while attenuating adipogenic differentiation of rBMSCs. Therefore, we concluded that ERα and QUE might regulate the differentiation of rBMSCs through the circRNA-miR-326-5p-mRNA axis.

A label-free electrochemical magnetic aptasensor based on exonuclease III-assisted signal amplification for determination of carcinoembryonic antigen.

A novel label-free and exonuclease III (Exo III)-assisted signal amplification electrochemical aptasensor was constructed for the determination of carcinoembryonic antigen (CEA) via magnetic field-induced self-assembly of magnetic biocomposites (Fe3O4@Au NPs-S1-S2-S3). The magnetic biocomposites were acquired by modifying double-stranded DNA (S1-S2-S3) on the surface of Fe3O4@Au nanoparticles (Fe3O4@Au NPs). Among them, Fe3O4@Au NPs were used as carriers for magnetic separation, thiolated single-stranded DNA (S1) provided signal sequence, CEA aptamer (S2) worked as a recognition element, and complementary strand (S3) was used to form double strands. In the presence of CEA, S2 bonded with CEA competitively; the exposed S1 could not be cleaved since Exo III was inactive against ssDNA. The G-quadruplex/hemin complexes finally formed with the existence of K+, and the high electrochemical signal of G-quadruplex/hemin complexes was recorded by differential pulse voltammetry (DPV) at - 0.6 V. Conversely, in the absence of CEA, dsDNA was cleaved from the 3' blunt end by Exo III; the disappearance of G-rich sequence blocked the generation of the signal. This method exhibited good selectivity and sensitivity for the determination of CEA; the linear range was from 0.1 to 200 ng mL-1 and the limit of detection was 0.4 pg mL-1. Graphical abstract.