In this study, high-performance liquid chromatography coupled with tantrum mass spectrometry (HPLC-MS/MS) technology was employed to determine milrinone nitrogen oxides in milrinone. An ACCHROM XCharge-C18 column (100 mm × 2.1 mm, 5 μm) was used with a mobile phase consisting of A phase (methanol) and B phase (5 mmol/L NH4FA, pH3 adjusted by formic acid). Agilent 6410B triple quadrupole mass spectrometer was used for HPLC-MS/MS analysis. Detection was performed using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode to analyze the limit of milrinone nitrogen oxides in milrinone, and the quantitative transition for the ion pair was from m/z 228.01 to m/z 181.90. Experimental results showed that the method exhibited good specificity, and that neither blank solvent nor blank samples interfered with the determination of milrinone nitrogen oxides of milrinone. The method demonstrated high sensitivity, with a limit of quantitation (LOQ) of 0.0076 μg/mL and a limit of detection (LOD) of 0.0038 μg/mL. The linear range spanned from 20% to 200% of the LOQ concentration, and a good linear relationship between concentration and peak area was observed within this range. Additionally, the recovery rates were consistently within the range of 80% to 120%, and the RSD for repeatability tests was 12.0%. These results indicated that the precision and accuracy of this method meet the required standards. In summary, the method developed in this study can effectively and accurately determine the content of milrinone nitrogen oxides in milrinone.

By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 μg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.
Humans ; Mycotoxins/analysis* ; Coix ; Aflatoxin B1/analysis* ; Chromatography, Liquid/methods* ; Food Contamination/analysis* ; Tandem Mass Spectrometry/methods*

The present study counted the frequency of detection technologies and monitoring frequency of pesticide species by frequency analysis based on the 28 258 pieces of data on pesticide content of Chinese medicinal materials in CNKI, calculated the detection rate and exceeding rate of different types of pesticides, and systematically analyzed the pesticide residue pollution of Chinese medicinal materials. The results showed that there were 40 types of pesticides with detection rates higher than 10%, where new pesticides such as organochlorines and nicotine accounted for 55%, and organic phosphorus, pyrethroids, and carbamates accounted for 17.5%, 15.0%, and 12.5%, respectively. Seventeen types of pesticides exceeded the standard to varying degrees, including 12 types(70.59%) with exceeding rates not higher than 5%, four types(23.53%) with exceeding rates in the range of 5%-10%, and one type(5.88%) with an exceeding rate higher than 10%. As revealed by the analysis results of the past five years, the pesticide residue pollution of Chinese medicinal materials showed a downward trend. Compared with the conditions at worst, organochlorines decreased by about 2/3 in detection rate and 47.23% in exceeding rate, carbamates by about 1/2 in detection rate and 10.78% in exceeding rate, organic phosphorus by 3/4 in detection rate and 7.22% in exceeding rate, pyrethroids by 1/2 in detection rate and 11.05% in exceeding rate, and other types by about 1/2 in detection rate but not exceeded the standard. In general, pesticide residues in Chinese medicinal materials and safety have been significantly improved. However, pesticide residues are still important factors affecting the quality and safety of Chinese medicinal materials. It is suggested to further improve the control standards of pesticide residues in Chinese medicinal materials, strengthen the monitoring of pesticides used in practical production, and promote the ecological planting mode to facilitate the high-quality development of the Chinese medicinal material industry.
China ; Hydrocarbons, Chlorinated/analysis* ; Pesticide Residues/analysis* ; Pesticides/analysis* ; Pyrethrins/analysis*

AIM:To identify the reasons for not improving visual acuity of patients with diabetic macular edema(DME)and its correlation with optical coherent tomography(OCT)imaging characteristics. They were treated with anti-vascular endothelial growth factor(VEGF)again after an interruption of treatment due to the COVID-19 pandemic.METHODS: Retrospective cases study. A total of 31 patients(40 eyes)with DME and treated with anti-VEGF drugs in the Department of Ophthalmology of the First Affiliated Hospital of Xi'an Jiaotong University between December 2019 and July 2020 were selected. All patients had an treatment history of interruption due to COVID-19. Based on the behavioral standard of best corrected visual acuity(BCVA)at 1mo after re-treatment, they were divided into improved visual acuity group(14 eyes)and non-improved visual acuity group(26 eyes). All patients received comprehensive ophthalmic examinations, including BCVA, intraocular pressure, OCT, fundus photography, and fundus fluorescein angiography(FFA). The central retinal thickness(CRT), hyper-reflective retinal dots(HRD), subretinal fluid(SRF), intraretinal fluid(IRF), disorganization of the inner retinal layers(DRIL)and ellipsoid zone disruption(EZD)were quantified by Image J. The correlation between BCVA and CRT, the number of HRD, the diameter of SRF and IRF, and the height of DRIL and EDZ width at 1mo after treatment were analyzed by Spearman correlation.RESULTS: The proportion of HRD in OCT was significantly higher in the non-improved visual acuity group than that in the improved visual acuity group(χ2=5.43, P=0.0072); There was a positive correlation between the difference of BCVA(LogMAR)and CRT change in DME patients after treatment(rs=0.406, P=0.009); There was a positive correlation between BCVA(LogMAR)and EZD width after treatment(rs=0.358, P=0.023). There was no correlation between BCVA(LogMAR)after treatment and the number of CRT(rs=-0.086,P=0.600)and HRD(rs=-0.115,P=0.482), the diameter and height of SRF(rs=0.102,P=0.530; rs=0.100,P=0.538)and IRF(rs=0.134,P=0.410; rs=-0.014,P=0.932), and the width of DRIL(rs=0.089,P=0.587).CONCLUSION:The probability of retinal HRD was significantly higher in patients with no visual improvement than that in patients with visual improvement after the re-treatment with anti-VEGF due to the treatment interruption during COVID-19. EZD width was also closely correlated to the prognosis of visual acuity. As for these patients, HRD manifestations in OCT should be comprehensively considered, taking intravitreal injection of glucocorticoid as an auxiliary strategy if necessary.

Breast Feeding ; Cesarean Section ; Female ; Humans ; Infant, Newborn ; Lactation ; Massage ; Postpartum Period ; Pregnancy

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

OBJECTIVE: To study the gene sequence characteristics of hantavirus in Heilongjiang Province in order to find out the reasons for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang Province in recent years.METHODS: Totally 110 rat lung specimens,121 blood specimens from patients diagnosed with mild or atypical HFRS and 100 blood specimens from patients diagnosed with typical HFRS in the First Affiliated Hospital of Harbin Medical University and the Seventh Hospital of Qiqihar City from 2005 to 2015 were collected. The gene sequences were obtained by nucleic acid extraction, RT-NestPCR, and gene sequencing. Explore the possible reasons for the changes in clinical characteristics of HFRS by comparing the obtained sequences with previous strains, homology analysis, building phylogenetic trees of M gene, and finding out the law of nucleotide and amino acid loci changes. RESULTS: TM gene of twenty-six mild or atypical HFRS patients were successfully amplified, including 14 cases of HTN type and 12 cases of SEO type; M gene of twenty-two typical HFRS patients were amplified, including 19 cases of HTN type and 3 cases of SEO type. Compared with the standard strain 76-118, the nucleotide homology of hantavirus from mild or atypical HFRS patients, typical HFRS patients and mice was 74.4%-89.2%, 87.4%-90.3% and 88.1%-88.5%. Comparing hantavirus gene sequence from mice and from patients, the nucleotide homology was 79.7-99.1%. Hljh38 and Hljh39 from patients were significantly different from the other strains. They were the same subtype as Amur virus because they had high homology with Amur strains H5 and H8205(94.9%-97.6%). The deduced amino acids showed some variations compared with the standard strains, but no obvious variation law was observed. CONCLUSION: The reason for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang province is related to the change of viral type. There are also variations of hantavirus and amino acid, but the relationship between specific variation law and clinical manifestations needs to be further verified.