Objective To provide a specific,sensitive,reproducible HPLC method for the determination of doxepin in urine and whole blood with doxapram as the internal standard.Methods The sample preparation was simple and time-saving by using an Oasis pretreatment cartridge.Separations were achieved by a Lichrospher  100 RP-18e (250mm?4.0mm,5?m)column kept at 50 ℃,and the DAD detector was set at 230nm and 250nm.Results The detection limit was 2 ng/ml in urine and whole blood.The results showed excellent linearity.The relative standard deviation of between-day and within-day assay was Less than 6.75%,and absolute recoveries were higher than 85%.Conclusion The method for determination of doxepin in urine and whole blood is effective,simple and reliable,which may be applicable to the practical cases.

Objective To retrospectively analyze the clinical epidemiology features of adult idiopathic membranous nephropathy (IMN) in Zhongshan Hospital,and to investigate their therapeutic effect and its possible influence factors.Methods A total of 183 patients admitted to the Zhongshan Hospital of Fudan University and diagnosed as IMN by renal biopsy from January 2013 to December 2015 were involved.Their baseline information including demographics and pathologic was collected.Patients were followed up for at least 12 months.Serum albumin ＜ 30 g/L and 24 h urine protein ＞ 3.5g were defined as nephrotic syndrome (NS).IMN patients were divided into NS and non-NS groups and compared.Furthermore,the baseline data of remission and no remission patients were compared,and the correlations of their baseline data with conservative and immunosuppressive therapy were assessed by logistic regression analysis.Results (1) IMN accounted for 11.1％ of renal biopsy cases in our hospital,with an average age of 57 years and 59.6％ male patients.(2) Compared with patients without NS,IMN patients with NS were older,had a shorter time from the onset to receive renal biopsy,lower estimated glomerular filtration rate,and higher total cholesterol,low density lipoprotein cholesterol,triglyceride and serum creatinine (all P ＜ 0.05).(3) The effective rate of conservative treatment in IMN patients without NS was 65.7％,and the ineffective group had higher triglyceride compared with the effective group (P=0.019).(4) The effective rate of immunosuppressive therapy in IMN patients with NS was 81.2％,and low serum albumin was an independent risk factor for the poor efficacy of immunosuppressive therapy (OR=1.202,95％ CI 1.003-1.440,P=0.046).(5) The effective rate of conservative treatment in IMN patients with NS was 55.5％,and low serum albumin was an independent risk factor for the poor efficacy of conservative treatment (OR=1.629,95％CI 1.047-2.536,P=0.023).Conclusions The detection rate of IMN is increasing year by year,but the remission rate of conservative treatment is still not low in mild and moderate patients.For the patients without NS,high triglyceride may predict a poor effect of conservative treatment.Hypoproteinemia is a predictor of poor effect,no matter what a NS patient takes immunosuppressive therapy or conservative treatment.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.