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

Objective:To investigate and analyze case reporting ethical review and patient informed consent reports published in the comprehensive journals of clinical medicine in China in 2022.Methods:According to the data from the 2022 Edition of the Chinese Science and Technology Journal of the Citation Reports(Extended Version),the case reports published in comprehensive journals of clinical medicine in 2022 were selected as the research objects.The information on ethics and patient informed consent was extracted from the case reports that met the selection criteria,and Microsoft Excel 2021 and SPSS 21.0 were used to sort out and analyze the data.Results:A total of 587 case reporting articles were published in the 42 included journals in 2022,of which 36(6.13%)reported on science and technology ethics and/or informed consent.Case reports reporting on science and technology ethics and/or informed consent mostly came from the key magazine of China technology(88.89%Vs.65.88%),and the proportion of manuscripts involving science and technology ethics on the official website of the journal was relatively high(86.11%Vs.63.88%),and the difference was statistically significant(P＜0.01).Conclusion:The proportion of case reports of science and technology ethics and/or informed consent in journals of comprehensive discipline classification of clinical medicine was relatively low.Currently,most international journals are required to obtain the informed consent of patients or legal guardians before publishing case reports.Compared with this,there are still certain gaps in China,which need to be paid great attention to.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

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.

Objective:To evaluate the effectiveness of correcting breast ptosis using the rotational filling of an inferolaterally pedicled tongue-shaped parenchymal flap via a double periareolar incision.Methods:A retrospective study was conducted on 34 female patients (68 breasts) with breast ptosis treated at the Department of Plastic Surgery at the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from January 2016 to June 2023. The patients＇ ages ranged from 23 to 53 years, with an average of (37.4±7.9) years. All patients underwent correction of breast ptosis using an inferolaterally pedicled tongue-shaped parenchymal flap via a double periareolar incision. Pre-operative and post-operative measurements were taken to assess the corrective outcomes, including mammary base width (MBW), areola diameter (AD), nipple-to-nipple distance (NN), suprasternal notch-to-nipple distance (SSN-N), nipple-to-inframammary fold distance (N-IMF), and thoracic circumference at the nipple level (TN). Patients＇ satisfaction was assessed using the BREAST-questionnaire (BREAST-Q) module.Results:Postoperative first-stage wound healing was achieved in all 34 patients without complications such as hematoma, infection, or nipple necrosis. The follow-up period ranged from 6 to 60 months, with a median of 12 months. Early postoperative observations showed periareolar folds, which disappeared within 3 to 6 months in 31 cases, while mild periareolar folds, persisted for up to 12 months in 3 cases. Four patients reported reduced nipple sensation postoperatively. Measurements showed a statistically significant increase in TN and a reduction in NN, SSN-N, AD, N-IMF, and MBW compared to preoperative values (all P<0.001). BREAST-Q scores indicated significant improvements in satisfaction with breasts, psychosocial well-being and physical well-being, with preoperative scores of (21.6±8.9), (42.4±11.9) and (49.7±12.9) scores increasing to (82.3±8.5), (81.9±8.1) and (81.2±8.3) scores, respectively (all P<0.001). Conclusions:The double periareolar incision technique with rotational filling of an inferolaterally pedicled tongue-shaped glandular flap is a safe and effective method for correcting breast ptosis.

Objective To systematically review the efficacy of multiple doses and single dose of perioperative dexamethasone on pain and recovery after total knee arthroplasty(TKA).Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,SinoMed and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on multiple doses and single dose of dexamethasone during perioperative period of TKA from inception of the databases to January 4,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed by using RevMan 5.4 software.Results A total of 6 studies involving 674 patients were included,336 patients in single dose dexamethasone group and 338 patients in multiple dose dexamethasone group.The results of Meta-analysis showed that compared with single dose of dexamethasone,multiple doses of perioperative dexamethasone could significantly decrease the pain scores at rest at 48 h after TKA(SMD=-0.68,95%CI-1.05 to-0.30,P﹤0.001),the pain scores with movement at postoperative 48 h(SMD=-0.86,95%CI-1.37 to-0.34,P=0.001),C-reactive protein(CRP)levels at postoperative 48 h(MD=-4.43,95%CI-6.70 to-2.16,P﹤0.001)and CRP levels at postoperative 72 h(MD=-3.60,95%CI-5.53 to-1.67,P﹤0.001).There was no statistically significant difference between the two groups regarding pain scores at rest at postoperative 24 h and 72 h,pain scores with movement at postoperative 24 h and 72 h,incidence of postoperative nausea and vomiting(PONV),CRP levels at postoperative 24 h,length of hospital stay,and incidence of adverse drug reactions(P>0.05).The results of 5 studies showed that multiple doses of dexamethasone did not increase the dosage or patient proportion of remedial analgesics.Conclusion Current evidence shows that compared with single dose of dexamethasone,multiple doses of perioperative dexamethasone can significantly reduce pain scores at postoperative 48 h,CRP levels at postoperative 48 and 72 h after TKA,but it does not significantly reduce the incidence of PONV,hospital stay,or increase the risk of adverse drug reactions.

Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the pa-rameters in the diagnosis of anxiety and depression in PD patients.Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The gener-alized anxiety scale(GAD-7)and the patient health questionnaire(PHQ-9)were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were col-lected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW)were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients.Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0% ,respectively.There were differences in the dialysis period(Z=-2.358,P =0.018;Z =-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z =-4.587,P<0.001;Z=-7.367,P<0.001)between the anxiety group and the non-anxiety group as well as between the de-pression group and the non-depression group.The correlation analysis showed that MPV(r =0.358,P<0.001;r =0.489,P<0.001)and PDW(r =0.340,P<0.001;r =0.447,P<0.001)were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P =0.022,P =0.011),PDW(P =0.041,P =0.018),and dialysis period(P =0.011,P =0.030)were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively.Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.