Correlations between pruritus and CC chemokine ligand 17 in patients with mycosis fungoides / 中华皮肤科杂志

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

Establishment of a concentration test method of S-071031B in rat plasma and its pharmacokinetics / 军事医学

Objective To establish an LC-MS/MS method for determination of S-071031 B, a novel antidepressant , in rat plasma and to study its pharmacokinetic profiles .Methods An LC-MS/MS method was established to determine S-071031B in rat plasma, and L-8021 was employed as the internal standard .The analytes were separated on a C18 column with a mobile phase consisting of water-acetonitrile containing 0.1%(v/v) formic acid at a flow rate of 0.3 ml/min.The mass spectrometer was operated in a selected reaction monitoring ( SRM ) mode with a positive electrospray ionization (ESI) interface.The plasma concentration-time curve was drawn and pharmacokinetic parameters were calculated by DAS 2.0.Results The linear range was from 2 to 1000 ng/ml with a sensitivity of 2 ng/ml as the lower limit of quantification . The intra-day and inter-day precisions , recoveries and matrix effects at three spiked levels were all suited to the determina-tion of biological samples.After oral administration of S-071031B, the Cmax of S-071031B was (287.2 ±50.8) μg/L and the Tmax was (0.8 ±0.3) h, with a t1/2of (2.9 ±0.6) h and an AUC(0-∞)of (1372.6 ±255.3) μg/L· h.Conclusion This method is sensitive and specific enough for determination of S-071031 B in rat plasma to facilitate the study of its phar-macokinetics .

Determination of morroniside concentration in rat plasma by high performance liquid chromatography-tandem mass spectrometry / 中国中药杂志

Morroniside, an iridoid glycoside extracted from Cornus officinalis, has multiple pharmacological effects such as neuroprotection. This study took the lead in establishing a method for determining morroniside concentration in rat plasma by high performance liquid chromatography-tandem mass spectrometry. Plasma samples were processed with protein precipitation method, with hyperoside as the internal standard. An Inertsil C8-3 column (2. 1 mm x 50 mm, 5 microm) was adopted, with a mobile phase composed of water (containing 1 mmol L-1 Sodium formate)-acetonitrile (gradient elution) at a flow rate of 0.4 mL . min -1. Electrospray ionization (ESI) was adopted in the positive ion mode for multi-reaction monitoring (MRM). Morroniside showed a good linear relationship ranging between 2-5 000 microg L-1 (r = 0. 995 7), with the minimum limit of quantification of 2 microg L-1. Its precise, accuracy, recovery and matrix effect were all in line with the biological sample measurement requirements. Therefore, the method described above was proved to be suitable for the determination of morroniside concentration in rat plasma. To use the method in the pharmacokinetic study on morroniside in rats, oral administration dose shall be set at 20 mg . kg - to map the plasma concentration-time curve. Main pharmacokinetic parameters were calculated by DAS 2. 0. Specifically, AUC0-inifinity was (587.6 +/- 290. 7) microg min L-1, Cmax was (334.2+/-148.0) microg L-1, Tmax was (0.6 +/-0.3) h, t1/2 was (0.7+/-0.3) h.

Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5 / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>There is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome (RCAD)/maturity onset diabetes of the young type 5 (MODY5). The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominant TCF2 anomalies.</p><p><b>DATA SOURCES</b>MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification (hypomethylation and hypermethylation), loci associated with cancer risk, and somatic TCF2 anomalies were all excluded.</p><p><b>STUDY SELECTION</b>After searching the literature, 50 articles were selected.</p><p><b>RESULTS</b>The detection rate of TCF2 anomalies was 9.7% and varied considerably among MODY (1.4%), renal structure anomalies (RSA) (21.4%) and RSA with MODY (41.2%) subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain: exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA (89.6%) and diabetes mellitus (DM) (45.0%). However, the concurrence of RSA and DM was relatively low (27.5%), which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients with TCF2 anomalies. Analysis of phenotypes of TCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function (IRF) and DM according to mutation type but not mutation location.</p><p><b>CONCLUSION</b>These valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.</p>

Analysis on the Application of Narcotic Analgesics in Our Hospital During 2003～2007 / 中国药房

OBJECTIVE: To investigate the clinical application and developing trend of narcotic analgesics in our hospital.METHODS: Analgesics used in our hospital during 2003～2007 were analyzed statistically.RESULTS: The consumption(amount of money and quantity) of narcotic analgesics especially that of morphine preparation witnessed an year-on-year increase while that of pethidine injection decreased year by year.CONCLUSION: The use of narcotic analgesics in our hospital was reasonable on the whole,but the dosage form and variety should be increased further.