A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.

BACKGROUND:The laser applied in the clinical oral medicine is mainly for early diagnosis of caries, removal of carious tissue, pulpotomy for pulp bleeding, dentin hypersensitivity treatment, disinfection of infected root canals, and periodontitis treatment. OBJECTIVE:To explore the changes of basic fibroblast growth factor in inflammatory pulp after laser treatment. METHODS:Five healthy adult beagle dogs were enroled, and six teeth were randomly selected from each dog. Then, these teeth were randomly divided into three groups, 10 teeth in a group, and they were treated with laser irradiation, saline and gentamicin irrigation respectively. At days 1, 2, 3 after operation, exudates from the pulp were colected for detection of basic fibroblast growth factor expression. Meanwhile, the dental pulp was detected by hematoxylin-eosin staining and immunohistochemistry method. RESULTS AND CONCLUSION:In the al three groups, the expression of basic fibroblast growth factor at day 3 was significantly higher than that at days 1 and 2, and there were no differences between days 1 and 2. Moreover, these three groups also showed no significant differences. Under hematoxylin-eosin and immunohistochemical staining, blood vessels in the pulp cavity were in good condition and the pulp arranged tightly. These findings suggest that the laser is safe, convenient and effective for oral clinical application, and has no injury to the inflammatory pulp.

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.

Objective:To investigate the effect of Early infarct growth rate(EIGR) on the prognosis of patients with acute large vessel occlusive ischemic stroke.Methods:A total of 164 patients with acute large vessel occlusive ischemic stroke were enrolled in the emergency department of the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to December 31, 2022.According to the change of the National Institutes of Health Stroke Scale (NIHSS) score at admission and 72 h after treatment, the patients were divided into good prognosis group and poor prognosis group. The basic clinical data of the two groups were observed and compared. The risk factors of poor prognosis were analyzed by univariate regression. The effect of EIGR on prognosis after age stratification was further analyzed.Results:Comparing the clinical data of the two groups, there was no difference in EIGR (mL/h) (7.67 vs. 8.24, P=0.211) between the two groups. The product between EIGR and age was included as the interaction term, and the result of the interaction term in the model was statistically significant ( OR=1.002, 95% CI: 1.000-1.003, P=0.032) .Moreover, the result was still statistically significant after adjusting for relevant variables (gender, history of hypertension, history of atrial fibrillation, history of diabetes, history of coronary heart disease, and history of stroke) ( OR=1.002, 95% CI:1.000-1.003, P=0.027). Subgroup analysis was performed according to the median age (71 years). In the elderly group, the proportion of poor prognosis was higher with fast core infarction growth rate defined by 25 mL/h and 15 mL/h ( P < 0.05).In the younger age group, there was no significant difference in the proportion of poor prognosis in the fast core infarction growth rate compared with the slow type ( P > 0.05). Conclusions:EIGR can predict the early clinical outcome early in elderly patients with large vessel occlusive ischemic stroke.

Objective: By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases. Methods: By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape. Results: There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway. Conclusions The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis.