In this study, a composite cell model for evaluation of idiosyncratic drug-induced liver injury (IDILI) was established in vitro from the perspective of immune inflammation. And this model was used to evaluate the risk of IDILI for 2,3,5,4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside (Cis-SG) and 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside (Trans-SG). To determine the low, medium, and high dosage of Cis-SG and Trans-SG, CellTiter-Glo^® 3D Cell Viability Assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of HepG2 cells in three dimensional (3D) culture, and MTT assay was used to detect the effects of Cis-SG and Trans-SG on cell viability of THP-1 derived macrophages. THP-1 derived macrophages were incubated by Cis-SG and Trans-SG directly or supernatants from HepG2 cells incubated with them. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-1β (IL-1β) in the supernatants of the THP-1 derived macrophages. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in THP-1 derived macrophages. The results showed that there was no effect on the secretion of IL-1β in THP-1 derived macrophages incubated by Cis-SG and Trans-SG directly. However, the secretion of IL-1β, the protein and mRNA expression of ASC, NLRP3, caspase-1, and IL-1β significantly increased in THP-1 derived macrophages incubated by supernatants from HepG2 cells incubated with 1, 5, and 25 μmol·L^-1 Cis-SG or 25 μmol·L^-1 Trans-SG. In summary, the composite cell model for evaluation of IDILI established in vitro has been successfully applied in testing Cis-SG and Trans-SG. This composite cell model is helpful to evaluate and screen drugs with IDILI risk in vitro preliminarily, which provides methods for predicting and solving the idiosyncratic liver toxicity of drugs.

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.

This article made a brief analysis of clinical adverse effects of cinnabar. Except for allergic reaction, almost all the adverse events of cinnabar were caused by unreasonable application. The majority of the poisoning cases were associated with excessive and/or long-term dosage, and improper preparation methods, such as decocting, heating or fumigating. Children showed to be prone to poisoning. The poisoning caused by unreasonable use of cinnabar should be considered to be drug alert, but not advert effect. And the toxicity of cinnabar could be avoided by normalizing the preparation method, controlling the dosage and duration.
Chemical and Drug Induced Liver Injury ; etiology ; Coma ; chemically induced ; Drug Compounding ; adverse effects ; Drug Incompatibility ; Drug Overdose ; Gastrointestinal Diseases ; chemically induced ; Humans ; Hypersensitivity ; etiology ; Mercury Compounds ; adverse effects ; poisoning ; Mercury Poisoning ; prevention & control ; therapy

Objective To evaluate the clinical efficacy and safety of compound polymyxin B ointment combined with desonide cream for the treatment of subacute or chronic eczema. Methods A multicenter, randomized, double?blind, parallel?group, controlled clinical study was conducted. Totally, 144 patients with subacute eczema and 144 patients with chronic eczema were enrolled into this study, and both randomly and equally divided into the test group and control group. The test group and control group firstly topically applied compound polymyxin B ointment and its vehicle respectively, then both topically applied desonide cream 3 hours later. The drugs or vehicle were applied twice a day in all the patients. Patients′ symptoms and signs (including degree of itching, inflammation, erosion/exudation and infiltration/thickening, as well as area of target lesions) were evaluated, and the time to onset and duration of itching?alleviating effect were recorded. The clinical efficacy and safety of treatments were analyzed and compared between the test group and control group. Results The total symptom and sign scores significantly decreased to different extents on days 7 and 14 in the test group(subacute eczema patients:6.09 ± 2.78 and 3.68 ± 3.18 vs. 13.44 ± 1.66; chronic eczema patients: 6.56 ± 2.68 and 4.38 ± 3.27 vs. 12.96 ± 1.16)and control group(subacute eczema patients:8.26 ± 3.17 and 5.28 ± 4.05 vs. 13.60 ± 1.75;chronic eczema patients: 8.84 ± 2.90 and 6.25 ± 3.78 and vs. 12.64 ± 1.18)compared with those at baseline. Moreover, the total symptom and sign score of patients with subacute or chronic eczema was significantly lower in the test group than in the control group on days 7 and 14(all P<0.05). A significant increment was observed in the degree of decrease in scores for itch, infiltration/thickening in patients with subacute eczema in the test group compared with that in the control group(all P<0.01), as well as in scores for itch, infiltration/thickening and area of target lesions in patients with chronic eczema in the test group compared with those in the control group (all P < 0.05). In addition, patients with subacute eczema in the test group showed significantly shorter onset and longer duration of itching?alleviating effect than those in the control group(both P<0.05). The time to onset of itching?alleviating effect was also significantly shorter in patients with chronic eczema in the test group than in those in the control group(P<0.000 1), but there was no significant difference in the duration of it between the two groups of patients with chronic eczema. Clinicians and patients were both more satisfied with therapeutic effects in the test group than in the control group(all P<0.05). Conclusions Topical compound polymyxin B ointment can increase the efficacy of topical desonide cream for the treatment of subacute or chronic eczema, especially subacute eczema. Compound polymyxin B ointment also shows a favorable therapeutic effect on itching and infiltration/thickening in patients with eczema.

Objective To evaluate the relationship between G894T(Glu298Asp) polymorphism in the endothelial nitric oxide synthase (eNOS)gene and essential hypertension in Chinese population from difierent regions.Methods Odds ratios(Ors) of G894T genotype and allele distributions in essential hypertension patients against healthy controls were analyzed.All the relevant studies were screened with poor-qualified studies eliminated.Meta-analysis software MIX(Meta-analysis with interactive explanations-version 1.71),was applied for investigating and analyzing heterogeneity among individual studies and summarizing the effects across studies,and the risk of publication bias was evaluated.Results A total of 1900 cases and 1216 controls from 10 studies were included.The heterogeneity between studies Was significant(P=0.013;P=0.011) and there were substantial sources of Publication bias(P=0.049;P=0.038).The pooled OR(with 95% CI) of GT+TT vs.GG genotype was 1.79(1.33-2.42)(Z=3.83,P<0.001),and the pooled OR (with 95% CI) of T vs.G allele Was 1.73(1.32-2.27)(Z=3.92,P<0.001).Conclusion In Chinese population,mainly the Hans ethnic group,894G→T mutation in the eNOS appeared to be related to essential hypertension.

As many traditional Chinese medicines have been founded to have protective effect on liver damage in recent years, they have also got involved in increasingly wide clinical application. Meanwhile, with the development of new hepatic protective formulations of traditional Chinese medicines, we have set increasingly higher requirements for quality control methods and measures. This essay summarizes the advance in studies on hepatic protective formulations of traditional Chinese medicine and their quality control methods in the combination of relevant domestic and foreign literatures, looking into the future of the development of new hepatic protective formulations of traditional Chinese medicines.
Animals ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; standards ; therapeutic use ; Humans ; Liver ; drug effects ; Liver Diseases ; drug therapy ; prevention & control ; Medicine, Chinese Traditional ; standards ; trends ; Phytotherapy ; standards ; Quality Control

Adult ; Age Factors ; China ; epidemiology ; Female ; Gallstones ; epidemiology ; Humans ; Male ; Prevalence ; Sex Factors

AIM: Accommodation is one of the most important functions of human eye, while its mechanism is still under discussion. This paper aimed to study accommodation mechanism with numerical simulation.METHODS: A simulation model was constructed to study the mechanism of accommodation based on the experimental data derived from published resources. The displacement and pressure are applied on the model to study the deformation of lens during accommodating.RESULTS: The simulation showed that, as the eye was accommodating, the thickness of the lens increased linearly,and the lens diameter decreased linearly. The optical power of the lens increased as the accommodation increased. This result was accord with the public facts in accommodation.Furthermore, the pressure was found to have a great influence on the shape of the lens and the optical power. The lens became thinner and flatter as the pressure increased and the pressure caused a remarkable increase of lens' optical power.CONCLUSION: The outcome of this paper is consistent with the Helmholtz's hypothesis on accommodation to some extent. The analytical model presented in this paper can be used in the theoretical study of the accommodation mechanism of the human lens.

OBJECTIVETo evaluate the early and mid-term outcome of surgical repair for post-ductal coarctation of the aorta (CoA) under normothermia without cardiopulmonary bypass.

METHODSClinical data from 15 patients (11 males, 4 females, mean age 18 +/- 10 years) undergoing surgical repair for post-ductal CoA under normothermia without cardiopulmonary bypass between January 1999 and December 2004 were analyzed retrospectively. There were 7 isolated cases, 7 cases associated with patent ductus arterious (PDA), 1 case with PDA and ventricular septal defects. Operation was performed under normothermia with partial cross-clamping of descending aorta in 8 cases, compete cross-clamping in 6 cases and temporary shunt in 1 case. Operative techniques adopted prosthetic bypass graft in 9 cases, Gore-Tex patch graft aortoplasty in 4 cases and stenosis resection with end-to-end anastomosis in 2 cases. PDA was ligated at single-stage in 8 cases. Ventricular septal defect was repaired at second stage in 1 case.

RESULTSNo early and late death. Hypertension occurred in 9 cases during early postoperative period but was normalized gradually in 5 cases without medication during follow-up period, from 6 months to 5 years. The arterial blood pressure of lower extremities increased significantly and no hoarseness, paraplegia occurred after operation. No recoarctation and aneurysm formation were found during follow-up.

CONCLUSIONSurgical repair of post-ductal CoA under normothermia without cardiopulmonary bypass is safe and effective, which is a procedure of choice for patients with isolated CoA, CoA associated with PDA, or with other intracardiac anomalies that are ready to be repaired at second-stage.

Adolescent ; Adult ; Aortic Coarctation ; surgery ; Cardiovascular Surgical Procedures ; methods ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Male ; Retrospective Studies ; Temperature ; Treatment Outcome

Objective:To evaluate the role of synapsin-Ⅰ phosphorylation in herkinorin-induced reduction of oxygen-glucose deprivation/restoration (OGD/R)-caused damage to cortical neurons and the relationship with conventional protein kinase C (cPKC)γ in newborn mice.Methods:Primary cortical neurons of cPKCγ + /+ and cPKCγ -/- mice (within 24 h after birth) were cultured for 7 days.Each type of neurons were then divided into 3 groups ( n=5 each) using a random number table method: control group (group C), OGD/R group and herkinorin group (group H). The neurons were subjected to oxygen-glucose deprivation (OGD) for 1 h followed by restoration of oxygen-glucose supply for 24 h. Herkinorin 10 μmol/L was added immediately after onset of OGD, the neurons were then incubated for 1 h, and herkinorin was washed out at the end of OGD in group H. At 24 h of oxygen-glucose restoration, cells were collected for measurement of the cell survival rate by methyl thiazolyl tetrazolium assay, and immunofluorescence was used to measure the number of neurites and the length of dendrites.Western blot was applied to detect the expression of phosphorylated synapsin-Ⅰ (p-synapsin-Ⅰ). Results:Compared with group C, the cell survival rate and the number of neurites were significantly decreased, the length of dendrites was shortened, and the expression of p-synapsin-Ⅰ was down-regulated in cPKCγ + /+ and cPKCγ -/- mice in group OGD/R and group H ( P<0.05). Compared with group OGD/R, the cell survival rate and the number of neurites were significantly increased, the length of dendrites was prolonged, the expression of p-synapsin-Ⅰ was up-regulated in cPKCγ + /+ mice in group H ( P<0.05), and no significant change was found in the parameters mentioned above in cPKCγ -/- mice in group H ( P>0.05). There was no significant differences in the expression of synapsin-Ⅰ in neurons among the three groups of cPKCγ + /+ mice and among the three groups of cPKCγ -/- mice ( P>0.05). Conclusion:Herkinorin can reduce OGD/R-caused damage to cortical neurons through decreasing cPKCγ membrane translocation and inhibiting synapsin-Ⅰ phosphorylation in newborn mice.