Objective To analyze the adverse reaction reports （ADRs） of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use. Methods ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on. Results In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury （37.84%）. The age of drug-induced liver injury was mainly over 46 years, totaling 195 （75.28%）. Drugs were mainly distributed in cardiovascular system medicine （44.02%）, anti-infective medicine （23.94%）and anti-tumor medicine （11.58%）. Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases （46.49%）. The main anti-infectious drugs were cephalosporins （29.03%）, carbapenem （19.35%）， antifungal （17.74%）and quinolones （11.29%）. Adverse reactions occurred within 6 days （69.88%）, the duration of adverse reactions was 1-2 weeks （31.66%）, and most patients were improved （47.88%） or cured （37.07%）. Conclusion For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

The production of healthy agricultural products has increased the demand for innovative and sustainable plant protection technologies, and the rapid advancement of nanotechnology has brought revolutionary breakthroughs to traditional agriculture. Nanocarrier-based drug delivery systems can not only significantly improve the utilization efficiency of pesticides, achieving enhanced efficacy and reduced application, but also decrease the pesticide residues and environmental pollution. Additionally, they have made breakthrough progress in the stability and persistence of RNA pesticides. This review summarized the research progress on nanopesticides and RNA pesticides, focusing on the mechanisms of nanocarriers in improving pesticide bioactivity and RNA interference (RNAi) efficiency. It also systematically summarized the types of nanomaterials and their applications in pest and disease management and provided an in-depth outlook for the future development of nanopesticides and RNA pesticides, which provided technical support for the high-quality development of agriculture in the future.
Pesticides/chemistry* ; Nanotechnology ; Nanostructures ; RNA ; Agriculture/methods* ; RNA Interference ; Drug Delivery Systems

Poor ovarian response (POR) is a pathological condition in which the ovary responds poorly to gonadotropins,and is a major constraint on the unsatisfactory outcome of in vitro fertilization-embryo transfer (IVF-ET). Follicular growth,development,maturation,and expulsion are all affected by the yin-yang balance between heart and kidney,as well as the elevation exchange. If the heart and kidney essence and blood are insufficient,water and fire are out of harmony,and qi movement is not smooth,fewer high-quality follicles will be recruited and acquired during the ovarian stimulation cycle,resulting in a low transferable embryo rate and unacceptable pregnancy result. Sympathetic treatment of heart and kidney should be based on the following principles at different stages of the IVF-ET cycle:replenishing the heart,kidney,essence,and blood before entering the cycle,in order to nourish the essence and assist in the growth of the follicles;nourishing renal water,and clearing heart fire during the pituitary down-regulation period,in order to lessen the negative effects of the down-regulation medicinals;regulating the depression of the heart,liver,spleen,and kidney meridians during the follicle's retrieval period,in order to encourage the smooth release of the ova;and warming heart and kidney fire to improve endometrial tolerance during the implantation period. The application of the theory of intercourse of heart and kidney to elucidate the pathogenesis of POR is critical to the development of clinical strategies for fertility enhancement,as well as providing new ideas for the clinical application of traditional Chinese medicine in the field of reproduction.

Acute kidney injury （AKI） is a clinical syndrome characterized by a rapid decline in renal function over a short period due to various etiologic factors. If left untreated， AKI can progress to chronic kidney disease （CKD） or even end-stage renal disease （ESRD）. Although continuous renal replacement therapy （CRRT） can manage severe AKI， effective pharmacological treatments for AKI remain largely unavailable. Chinese medicine， with its multi-target and multi-pathway approaches， has accumulated substantial theoretical and practical knowledge in treating AKI and related complications. Rehmanniae Radix is a commonly used Chinese medicinal， known for its functions in clearing heat， cooling blood， nourishing yin， and promoting fluid production. The primary active ingredients of Rehmanniae Radix include catalpol， acteoside， and aucubin. In this study， we summarized recent research on the effect of the active ingredients of Rehmanniae Radix in preventing and treating AKI. We found that the key mechanisms underlying its anti-AKI effects include amelioration of inflammation， alleviation of oxidative stress， and inhibition of apoptosis. Additionally， the antifibrotic properties of the active ingredients of Rehmanniae Radix suggest its potential in slowing CKD progression. We reviewed the mechanisms of Rehmanniae Radix in treating AKI and its antifibrotic effects to provide a scientific basis for developing new AKI drugs， promoting the utilization of Rehmanniae Radix resources， and reducing the transition from AKI to CKD.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.

Objective To observe the value of parallel acquisition technique(PAT)combined with deep learning reconstruction(DLR)for shoulder joint MRI.Methods Totally 74 subjects who underwent shoulder joint MR scanning were prospectively enrolled.Shoulder joint MRI were acquired using standard sequence(group A),PAT accelerated sequence(group B)and PAT accelerated sequence combined with DLR(group C),respectively.Subjective evaluation of overall image quality,artifacts and clarity of anatomical structures(including articular cartilages,ligaments and bone marrow)were performed using a 5-point scale,and signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of articular cartilages were calculated for objective evaluation,which were then compared among groups.Results No significant difference of the subjective scores of overall image quality,artifacts nor clarity of anatomical structures was found between group A and C(all P＞0.05),which were all higher than those in group B(all P＜0.05).SNR and CNR of articular cartilages of shoulder joint MRI in group C,A,B decreased in order(all P＜0.05).Conclusion PAT combined with DLR could shorten scanning time of shoulder joint MRI,reduce image noise and improve image quality.

Objective To investigate the effect of matrine on apoptosis and oxidative damage of PC12 cells induced byβ-amyloid protein(Aβ)25-35 in Alzheimer disease and to analyze the mechanism of its interaction with the AMP-activated protein kinase(AMPK)/silenced information regulator(SIRT1)pathway.Methods The effect of matrine on the growth of PC12 cells was determined using MTT.Matrine concentrations of 0.5,1.0,and 1.5 mmol/L were selected for the experiment.PC12 cells were divided into the Con group(blank culture cells),the Aβ25-35 group(20 μmol/L Aβ25-35 treated cells),the Aβ25-35+Matrine-L group,the Aβ25-35+Matrine-M group,and the Aβ25-35+Matrine-H group(20μmol/L Aβ25-35 were treated with 0.5 mmol/L,1.0 mmol/L,and 2.0 mmol/L matrine).Cell proliferation was detected using MTT.The detection of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)using enzyme-linked immunosorbent assay,expression of B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved caspase-3 containing cysteine,and AMPK/SIRT1 pathway-associated proteins were detected using Western blotting.Results Compared to the Con group,OD value,Bcl-2 protein expression,SOD,and GSH-Px activity decreased at 24 h and 48 h;the apoptosis rate,Bax,cleaved caspase-3 protein expression,ROS content,IL-6,IL-1β,and TNF-α expression increased,and P-AMPK and SIRT1 protein expression were up-regulated in the Aβ25-35 group(all P<0.05).Compared to the Aβ25-35 group,OD value,Bcl-2 protein expression,SOD,and GSH-Px activities in the Aβ25-35+Matrine-L group,the Aβ25-35+Matrine-M group,and the Aβ25-35+Matrine-H group increased at 24 h and 48 h.Apoptosis rate,Bax,cleaved caspase-3 protein expression,and ROS content decreased.IL-6,IL-1β,and TNF-αexpression decreased,and p-AMPK,and SIRT1 protein expression were down-regulated(all P<0.05).Conclusion Matrine may reduce the apoptosis and oxidative damage of PC12 cells induced by Aβ25-35 by inhibiting the AMPK/SIRT1 pathway.