[The effect of four immunosuppressive drugs on oral manifestations after organ transplantation].

PURPOSE: To assess the prevalence of oral manifestations in a group of allogenic liver, kidney or haematopoietic stem cell transplantation recipients and patients, and analyze the possible oral manifestations associated with the use of 4 immunosuppressive drugs. METHODS: One hundred and eighteen patients submitted to liver, kidney and hematopoietic stem cell transplantation who used tacrolimus， sirolimus，cyclosporine or mycophenolate mofetil were enrolled. Through a questionnaire survey and oral examination, their oral manifestations were recorded, and the possible statistical associations with immunosuppressive drugs were analyzed using SPSS 21.0 software package. RESULTS: The prevalence of oral lichenoid lesions and cheilitis for the group of patients using tacrolimus after transplantation was significantly lower than the group of patients who did not used the agent(P＜0.01). The prevalence of oral lichenoid lesions for the group of patients who used cyclosporine was significantly higher than the group of patients who did not used the drug(P＜0.05), and the prevalence of cheilitis for the group of patients who used cyclosporine was significantly higher than the group of patients who did not used the drug(P＜0.01). The prevalence of oral lichenoid lesions and cheilitis for the group of patients who used tacrolimus was significantly lower than the group of patients who used cyclosporine(P＜0.01). The group of patients who used mycophenolate mofetil after transplantation had a significantly lower prevalence of dry mouth than the group of patients who did not used the drug(P＜0.01). The prevalence of oral manifestations in patients with sirolimus after transplantation was not significantly reduced. CONCLUSIONS: The use of tacrolimus improved the symptoms of oral lichenoid lesions and cheilitis and the effect was better than cyclosporine after transplantation. The use of mycophenolate mofetil improved dry mouth after organ transplantation.

Self-assembled dehydropeptide nanocarrier as a delivery system for antitumor drug temozolomide.

Stable molecular conformation and intermolecular forces are essential for peptide self-assembly. In this study, one novel dehydropeptide (DDP) monomer (Boc-(Z)Cα,ß-ΔPhe-Gly-NHMe, DDP 1) was prepared; its conformation was confirmed to be more stable than the normal peptide 2 by nuclear magnetic resonance (NMR) and X-ray crystal diffraction experiments. DDP 1 was self-assembled to one novel dehydropeptide nanomaterial (DDPN 1). Fourier transform infrared (FTIR) spectroscopy results showed that hydrogen bonding was the main driving force of self-assembly. Electron microscope images displayed that the DDPN 1 fibers were longer and more stable than peptide 2 nanomaterials. Results of cell activity and enzyme hydrolysis proved that DDPN 1 had excellent biocompatibility and resistance to the enzymatic hydrolysis of protease K. Therefore, the DDPN 1 was used to load the antitumor drug temozolomide (TMZ). Due to intermolecular hydrogen bonds formed between TMZ and DDPN 1, TMZ-loaded DDPN 1 had a high percent entrapment efficiency (EE) of 83.72 ± 4.30% (n = 8) and a percent drug loading efficiency (LE) of 6.70 ± 0.34% (n = 8), and the half-life of TMZ-loaded DDPN 1 was 2.5-3 times longer than that of TMZ at pH 7. The in vitro cell viability results revealed that TMZ-loaded DDPN 1 exhibited higher antitumor activity (IC50 = 552.1 µM) against U118-MG than that of TMZ (IC50 = 1980.1 µM), possibly because that U118-MG cells uptook more TMZ from TMZ-loaded DDPN 1 than from free TMZ directly. This study is expected to inspire the design of biocompatible nanocarriers applied for anti-enzymatic hydrolysis in drug delivery systems.

Impact of B-lines-guided intensive heart failure management on outcome of discharged heart failure patients with residual B-lines.

AIMS: Pulmonary congestion (PC) expressed by residual lung ultrasound B-lines (LUS-BL) could exist in some discharged heart failure (HF) patients, which is a known determinant of poor outcomes. Detection efficacy for PC is suboptimal with widely used imaging modalities, like X-ray or echocardiography, while lung ultrasound (LUS) can sufficiently detect PC by visualizing LUS-BL. In this trial, we sought to evaluate the impact LUS-BL-guided intensive HF management post-discharge on outcome of HF patients discharged with residual LUS-BL up to 1 year after discharge. IMP-OUTCOME is a prospective, single-centre, single-blinded, randomized cohort study, which is designed to investigate if LUS-BL-guided intensive HF management post-discharge in patients with residual LUS-BL could improve the clinical outcome up to 1 year after discharge or not. METHODS AND RESULTS: After receiving the standardized treatment of HF according to current guidelines, 318 patients with ≥3 LUS-BL assessed by LUS within 48 h before discharge will be randomly divided into the conventional HF management group and the LUS-BL-guided intensive HF management group at 1:1 ratio. Patient-related basic clinical data including sex, age, blood chemistry, imaging examination, and drug utilization will be obtained and analysed. LUS-BL will be assessed at 2 month interval post-discharge in both groups, but LUS-BL results will be enveloped in the conventional HF management group, and diuretics will be adjusted based on symptom and physical examination results with or without knowing the LUS-BL results. Echocardiography examination will be performed for all patients at 12 month post-discharge. The primary endpoint is consisted of the composite of readmission for worsening HF and all-cause death during follow up as indicated. The secondary endpoints consisted of the change in the New York Heart Association classification, Duke Activity Status Index, N terminal pro brain natriuretic peptide value, malignant arrhythmia event and 6 min walk distance at each designed follow up, echocardiography-derived left ventricular ejection fraction, and number of LUS-BL at 12 month post-discharge. Safety profile will be recorded and managed accordingly for all patients. CONCLUSIONS: This trial will explore the impact of LUS-BL-guided intensive HF management on the outcome of discharged HF patients with residual LUS-BL up to 1 year after discharge in the era of sodium-glucose cotransporter-2 inhibitors and angiotensin receptor blocker-neprilysin inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05035459.

[Application of double plasma molecular adsorption system in children with acute liver failure].

OBJECTIVE: To study the efficacy and safety of double plasma molecular absorption system (DPMAS) in the treatment of pediatric acute liver failure (PALF). METHODS: A prospective analysis was performed on the medical data of children with PALF who were hospitalized in the Intensive Care Unit (ICU), Hunan Children's Hospital, from March 2018 to June 2020. The children were randomly divided into two groups:plasma exchange group (PE group) and DPMAS group (n=18 each). The two groups were compared in terms of clinical indices after treatment, laboratory markers before and after treatment, and adverse events after treatment. RESULTS: Compared with the PE group, the DPMAS group had a significantly lower number of times of artificial liver support therapy and a significantly shorter duration of ICU stay (P < 0.05), while there was no significant difference in the 12-week survival rate between the two groups (P > 0.05). There was no significant difference in laboratory markers between the two groups before treatment (P > 0.05). After treatment, both groups had reductions in the levels of total bilirubin, interleukin-6, and tumor necrosis factor-α, and the DPMAS group had significantly greater reductions than the PE group (P < 0.05). Both groups had a significant reduction in alanine aminotransferase (P < 0.05), while there was no significant difference between the two groups (P > 0.05). The PE group had a significant increase in albumin, while the DPMAS group had a significant reduction in albumin (P < 0.05). The PE group had a significant reduction in prothrombin time, while the DPMAS group had a significant increase in prothrombin time (P < 0.05). There was no significant difference between the two groups in the rebound rate of total bilirubin and the overall incidence rate of adverse events after treatment (P > 0.05). CONCLUSIONS: DPMAS is safe and effective in the treatment of PALF and can thus be used as an alternative to artificial liver support therapy.