The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

The microsphere drug delivery systems have been extensively exploited for providing controllable drug release kinetics, enhancing drug stability and localized drug delivery. In past decade, dozens of microsphere drug delivery systems have been developed for clinical therapy of cancer, schizophrenia and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinsonism). In this review article, we comprehensively summarized the fabrication methods of drug delivery systems and highlighted their advances for clinical application. Furthermore, we analyzed the potential and the challenges for clinical translation of the drug delivery systems.

AIM: To identify the pathogenic gene in a family with primary open angle glaucoma(POAG)from Nantong, Jiang Province, and to analyze its clinical phenotype and pathogenic mechanism.METHOD: A POAG pedigree was reviewed and recruited from January 2020 to December 2020, which spans 5 generations, with 33 people in total. A total of 13 family members were enrolled in our study, of whom 4 members were diagnosed with POAG, 1 with ocular hypertension(OHT), and the other 8 members were unaffected. Detailed medical history was collected and a comprehensive ophthalmic examination was performed. High throughput sequencing was used to screen for possible pathogenic gene, and Sanger sequencing was used to verify candidate pathogenic gene.RESULT: All patients in this family were found to have elevated intraocular pressure(IOP)and diagnosed with glaucoma at a young age, requiring surgical treatments to control the IOP. The highest IOP of proband was up to 55mmHg. A heterozygous mutation(c.1197C>A, p.Phe399Leu)of LTBP2 gene was found in the proband genome by whole exon sequencing(WES). Sanger sequencing verified that the mutation was not isolated from the family disease.CONCLUSION: LTBP2 (c.1197C>A)mutation was not the pathogenic gene of POAG in this family. However, the pathogenic potential of LTBP2 gene in POAG cases is worth studying.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake. Methods: DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD. Results: Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight. Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.
Animals ; Body Weight ; Organ Size ; Pyrones ; Rats ; Rats, Sprague-Dawley

Brucella ; Brucellosis/diagnosis* ; Chromatography, Affinity ; Gold Colloid ; Humans

OBJECTIVE: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. METHODS: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. RESULTS: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. CONCLUSION The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
Aeromonas/genetics* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Caenorhabditis elegans ; Cefazolin ; China/epidemiology* ; Diarrhea ; Drug Resistance, Multiple, Bacterial/genetics* ; Genetic Variation ; Humans ; Peptide Hydrolases/genetics* ; Virulence/genetics*

ObjectiveTo screen out the main targets and related signaling pathways of the herbal pair Cremastrae Pseudobulbus-Rhapontici Radix in treating breast cancer based on network pharmacology and verify their action mechanism in in vitro experiments. MethodThe main chemical components and related targets of Cremastrae Pseudobulbus-Rhapontici Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the target genes related to breast cancer from GeneCards. Following the screening of the common targets of Cremastrae Pseudobulbus-Rhapontici Radix and breast cancer using Venn， the Cremastrae Pseudobulbus-Rhapontici Radix-breast cancer network and protein-protein interaction （PPI） network were constructed. The effective targets were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis. The resulting outcomes were then verified by cell counting kit （CCK）-8 assay， flow cytometry， and Western blot. ResultThe screening yielded seven effective components and 61 targets of Cremastrae Pseudobulbus-Rhapontici Radix， among which 55 targets were involved in breast cancer. The GO analysis revealed 832 entries， which were mainly enriched in the biological processes. According to KEGG pathway enrichment analysis， 85 signaling pathways were obtained， including tumor suppressor p53， vascular endothelial growth factor （VEGF）， epidermal growth factor receptor （EGFR）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt）. It was verified in in vitro experiments that the alcohol extract of Cremastrae Pseudobulbus-Rhapontici Radix inhibited the proliferation of human breast cancer MDA-MB-231 cells and induced their apoptosis. Compared with the blank control group and the dimethyl sulfoxide （DMSO， 0.1% solvent） group， the medication groups exhibited obviously decreased absorbance in MDA-MB-231 cells （P<0.01） and increased apoptosis rate （P<0.01）. The results of Western blot demonstrated that compared with the blank control group and the DMSO group， each medication significantly reduced the phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in cells （P<0.05）. ConclusionThe ethanol extract of Cremastrae Pseudobulbus-Rhapontici Radix effectively inhibits the proliferation of human breast cancer MDA-MB-231 cells and induces their apoptosis， which may be related to the inhibition of the activation of PI3K/Akt signaling pathway.

Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ² value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ² value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult ; Allergens ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Pollen ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Rhinitis, Allergic, Seasonal ; Urbanization

Proliferative vitreoretinopathy(PVR)is a serious complication arisen from ocular trauma, diabetic retinopathy, vascular retinopathy, inflammatory retinopathy and other ocular diseases. It is also the most important reason for the failure of rhegmatogenous retinal detachment surgery, which is a great threat of visual function. A large number of studies have proved that the main risk factor for PVR is the damage of blood-retinal barrier, in which retinal pigment epithelial(RPE)cells are stimulated by cytokines in the vitreous cavity. RPE cells underwent epithelial-mesenchymal transition(EMT), which transformed into fibroblasts. The cell morphology changed, the tight junctions between cells disappeared, the cell polarity lost, and the proliferation, migration, and invasion abilities were enhanced. A contractile fibrous proliferative membrane is formed on the anterior surface or under the retina. The fibrous proliferative membrane will lead to the retina folds, pull the retina and lead to retinal detachment, which will eventually lead to vision loss or even blindness. Nowadays, plenty of studies investigating the prevention and treatment of PVR have been carried out at home and abroad. In this review, we briefly illustrated the signaling pathways related to epithelial-mesenchymal transformation in RPE cells and the treatment of PVR.