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To observe the efficacy and safety of roxadustat, an inhibitor of proline hydroxylase, in renal allograft anemia patients.This prospective study collected the clinical data of renal transplant patients treated with roxadustat for anemia at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from April to August 2020. The patients were followed up every 2 weeks, and the changes in their hemoglobin index and any adverse reactions were recorded during 10 weeks of treatment. The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment. Rates of treatment response and achievement of the standard hemoglobin level were statistically analyzed. In addition, any potential adverse events and the glomerular filtration rate were recorded for 10 weeks to assess the safety of roxadustat in renal allograft anemia patients.After 10 weeks of roxadustat treatment, the mean hemoglobin level was 10.4±3.9 g/dL, which was significantly higher than at baseline. Over the entire period, treatment was observed to have a therapeutic effect at weeks 2-4, with mean hemoglobin levels increasing as treatment time increased. At the 10-week endpoint, the percentage of patients reaching the standard hemoglobin level and exhibiting a response to treatment was 52.4% and 71.4%, respectively. During the treatment, there was no rejection, and the glomerular filtration rate was stable. Only one person showed symptoms of fatigue, and there were no other obvious adverse reactions reported.Roxadustat significantly improves hemoglobin levels and can be safely used in renal transplant anemia patients.

Hypofibrinogenemia is a serious adverse reaction related to tigecycline administered against multidrug-resistant (MDR) bacteria and can lead to therapy termination. High dose and prolonged tigecycline therapy, renal failure, and base level of fibrinogen (FIB) were reported risk factors of tigecycline-associated FIB reduction. But results are unknown in patients with renal transplantation.A single-center and a case-control study involving renal transplantation patients was conducted. From January, 2017 to January, 2020, patients with a tigecycline course more than 2 days and a baseline FIB level greater than 2 g/L were enrolled. Hypofibrinogenemia was defined as plasma FIB2.0 g/L. The extent of FIB reduction was calculated based on the baseline of FIB level before tigecycline administration. FIBRO was defined as the extent of FIB reduction over 50%, and FIBRB referred to the extent of FIB reduction below 50%. Univariate and multivariate analyses were performed by logistic regression models to identify independent risk factors of tigecycline-associated FIB reduction.In total, 120 patients were enrolled. A total of 114 patients (95.00%) developed with hypofibrinogenaemia. Hypofibrinogenemia mainly occurred 3 days after tigecycline administration. Of them, 79 (65.83%) developed FIBRO with a median occurrence of 3 [2-4] days after initiation of tigecycline. Multivariable regression analysis demonstrated that the FIB level before tigecycline use [odds ratio (OR): 3.225, 95% confidence interval (CI): 1.801-5.772] and total tigecycline dose (OR: 4.930, 95% CI: 1.433-16.959) were risk factors for FIBRO.The FIB level before tigecycline use and total tigecycline dose were significantly associated with FIBRO, suggesting that FIB level and coagulation-related indicators should be closely monitored during tigecycline treatment to avoid life-threatening bleeding events.

BACKGROUND: Currently, tacrolimus is the preferred anti-rejection therapy for kidney transplant recipients due to its greater protection against acute rejections compared to cyclosporin A (CsA). Despite the advantages of kidney transplantation, it has been associated with an increased incidence of de novo malignancies. Furthermore, a systematic review in 2005 revealed no statistical difference in tumorigenicity between tacrolimus and CsA. This report provides an up to date systematic review and evaluation of all relevant studies in the literature to determine the risk of malignancy in kidney transplant recipients exposed to tacrolimus. METHODS: A systematic literature search was performed using the Medline (PubMed and Ovid), Embase, Clinical Trials, and Cochrane databases (from creation to May 2021). We performed a meta-analysis of 11 studies with 36,985 kidney transplant recipients that compared the tacrolimus group with the control group. Outcomes of this study were incidence of malignancies and skin cancer risk. Risk of Bias was assessed in terms of whether there was random sequence generation, allocation concealment, blinding, completeness of results, selective reporting, etc. This meta-analysis was performed in accordance with PRISMA guidelines. RESULTS: Of the 11 included studies, 8 were high quality studies, 1 was assessed as medium quality, and 2 were low quality studies. The results showed a significantly increased risk of overall malignancy associated with tacrolimus exposure compared to non-tacrolimus therapy [risk ratio (RR) =1.59; 95% confidence interval (CI): 1.19–2.11; P=0.002], and especially with sirolimus (SRL) (RR =2.58; 95% CI: 1.62–4.09; P

Kuifen Ma,1 Yuanheng An,1 Xiaoyang Lu,1 Jianyong Wu2 1Department of Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jianyong Wu Email wujianyong1964@zju.edu.cnAbstract: The COVID-19 pandemic has lasted for more than one year, which caused much trouble to the health management of kidney transplant recipients. Numerous patients cancelled their review appointment or even lost connection with doctors because of the great pressure medical system undergoing, strict travel restrictions, and the worries about COVID-19 infection risk. Herein, we introduce two kidney transplant recipients, a 33-year-old man and a 32-year-old man, who did not take the immunosuppressant drugs and did not go back to the hospital to do the renal function examination as the doctor’s request. When they paid their first return visit several months after the pandemic outbreak, they were both diagnosed with acute rejection and admitted to the hospital. After receiving pulse steroid therapy, they were in remission but failed to reverse the rejection. The level of serum creatinine did not recover to the one before pandemic outbreak. These cases suggest that it is necessary to ensure that kidney transplant recipients follow the doctor’s advice to take drugs and follow-up regularly to examine their renal function over pandemic period. Additionally, typical pulse steroid therapy may not that effective toward these patients.Keywords: acute rejection, kidney transplantation, health management, COVID-19, compliance

In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD.A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to50, 50 to80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty.The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to50 mL/min), $9,758/QALY (50 to80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates.The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Background Depending on the renal function of patients and many other influencing factors, studies on vancomycin pharmacokinetics show significant inter- and intra-individual variability. The present study was conducted using a population pharmacokinetics method to investigate the pharmacokinetic parameters and identified their influencing covariates for intravenous vancomycin in adult kidney transplant recipients. Methods The drug monitoring data included 56 adult renal transplant recipients who received intravenous vancomycin as prophylactic medication. The analysis was performed by a population approach with NONMEM. Data were collected mainly during the first week after transplantation. Monitoring of vancomycin trough concentration in blood was initiated mainly 3-5 days after the initial administration. Results The one-compartment open model was optimal and adequately described the data. Body weight (WT) and estimated glomerular filtration rate (GFR) were identified as significant covariates of the pharmacokinetic parameters CL and V of intravenous vancomycin in the kidney transplant patients. The typical values of vancomycin CL and V were 2.08 L h-1 and 63.2 L, respectively. A dosage strategy scheme according to model results was also designed. Conclusion Both WT and GFR of the kidney transplant patients positively influence the pharmacokinetic parameters CL and V for intravenous vancomycin. Our population pharmacokinetic model provides a reference for vancomycin dosage adjustment in kidney transplant recipients.

An high-performance liquid chromatography-tandem mass spectrometry method has been optimised and established for the quality evaluation of the traditional Chinese medicine Dan Deng Tong Nao capsules through simultaneous determination of the following eight active components: danshensu, salvianolic acid A, salvianolic acid C, puerarin, scutellarin, apigenin, 3,4-dihydroxybenzaldehyde, and ferulic acid. All of the analytes were separated on a Waters Xbridge™ C18 column (4.6 × 150 mm, 3.5 µm particle size) with a mobile phase consisting of methanol/acetonitrile (50 : 50, v/v) and water containing 0.1 % formic acid. All of the compounds showed good linearity (R2 > 0.997). The recoveries, measured at three concentration levels, varied from 94.94 to 107.3 %. The validated method was successfully applied to evaluate the eight active components in Dan Deng Tong Nao capsules collected from different production batches. The results suggested that the method established in this study could be considered a good approach to controlling the quality of Dan Deng Tong Nao capsules and other related botanical drugs.

Junctophilin2 (JP2) is a critical protein associated with cardiogenesis. Icariin (ICA) facilitated the directional differentiation of murine embryonic stem (ES) cells into cardiomyocytes. However, little is known about the effects of ICA on JP2 during cardiac differentiation. Here, we explored whether ICA has effects on the expression and Ca2+ related function of JP2 during cardiomyocyte differentiation of ES cells in vitro. Embryonid bodies (EBs) formed by hanging drop were treated with 10(-7) mol/L ICA from day 5 to promote the cardiac differentiation. Percentage of beating EBs and number of beating area within EBs were monitored. Cardiomyocytes were purified by discontinuous percoll gradient centrifugation from EBs. The expression of JP2, α-actinin and troponin-T within EBs or isolated cardiomyocytes were analyzed by immunocytochemistry, western blot and flow cytometry. The transient Ca2+ release was characterized in cardiomyocytes treated with/without 10 mmol/L caffeine and 8 mmol/L Ca2+. Our results showed that ES cell-derived cardiomyocytes were well characterized with JP2 proteins. ICA promoted cardiomyocyte differentiation as indicated by an increased percentage of beating EBs and number of beating area within EBs. The expression of JP2, α-actinin and troponin-T were up-regulated both in EBs and isolated cardiomyocytes from EBs. Furthermore, ICA-induced JP2 expression was accompanied by a remarkable increase of the amplitude of Ca2+ transients in cardiomyocytes before/after caffeine and Ca2+ stimulating. In conclusion, ICA promotes in cardiac differentiation partly through regulating JP2 and improved the Ca2+ modulatory function of cardiomyocytes.

The metabolic syndrome is often associated with type 2 diabetes mellitus, dyslipidemia, atherosclerosis, hypertension, steatosis of the liver and other organs, as well as hypertension, type 2 diabetes mellitus, and atherosclerosis. Recent studies have implicated a number of inflammatory mediators including cytokines, adipokines and eicosanoids in the inflammatory responses that accompany the metabolic syndrome. Measurements of the circulating levels of the inflammatory molecules that accompany this syndrome might provide leads to therapeutic approaches to modulate the inflammatory responses and thereby alter disease progression. In this review, we summarize recent studies on classical and newer inflammatory mediators in the pathogenesis of the metabolic syndrome in humans and experimental models.

Since the introduction of microdialysis in 1974, the semi-invasive analytical method has grown exponentially. Microdialysis is one of the most potential analysis technologies of pharmacological drug delivery to the brain. In recent decades, analysis of chemicals targeting the brain has led to many improvements. It seems likely that fluorescence imaging was limited to ex vivo and in vitro applications with the exception of several intravital microscopy and photographic imaging approaches. X-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been commonly utilized for visualization of distribution and therapeutic effects of drugs. The efficient analytical methods for studies of brain-targeting delivery system is a major challenge in detecting the disposition as well as the variances of the factors that regulate the substances delivery into the brain. In this review, we highlight some of the ongoing trends in imaging modalities and the most recent developments in the field of microdialysis of live animals and present insights into exploiting brain disease for therapeutic and diagnostics purpose.

Endonuclease G (Endo G) is a novel determinant of cardiac hypertrophy. Here, we report the characterization of Endo G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy, and hypothesize that Endo G regulate mitochondrial function partly through Mfn2 and Jp2 during cardiac hypertrophy. Our results show that Endo G levels gradually increased at the beginning of phenylephrine-induced cardiac hypertrophy, accompanied by an abnormal mitochondrial membrane potential. The up-regulation of Mfn2, Jp2, and Endo G appeared at an early stage of cardiac hypertrophy, whereas PGC1α was not up-regulated until a later stage. Abolishing Endo G with siRNA led to the uncoupling of the mitochondrial electron transport chain from ATP production and decreased PGC1α expression, likely by affecting the juxtaposition of the mitochondria and the sarcoplasmic reticulum via Mfn2 and Jp2. Furthermore, abolishing Jp2 altered the expression of Endo G expression and induced mitochondrial dysfunction, suggesting that mitochondrial abnormalities in cardiac hypertrophy are most likely caused by Endo G. Taken together, our study established a link between Endo G and mitochondrial function during cardiac hypertrophy, partly through the effects of Endo G on Mfn2 and Jp2, and revealed a role for Endo G in the crosstalk between the processes controlled by Mfn2 and Jp2 in maladaptive cardiac hypertrophy.

Background Anakinra is the first interleukin-1 inhibitor to be used in clinical practice, and recent evidence showed that interleukin-1 plays a pivotal role in the pathogenesis of adult-onset Still disease (AoSD). However, data concerning efficacy with anakinra use in different clinical trials has not been evaluated, and the overall remission of AoSD with anakinra treatment has not been well defined. Methods We conducted a search on Embase, PubMed, and the Cochrane Library for relevant trials. Statistical analyses were conducted to calculate the overall remission rates, odds ratios (OR), and 95% confidence intervals (CI), by using either random effects or fixed effect models according to the heterogeneity. Results Of the 273 articles that were identified, 265 were excluded. Eight studies were eligible for inclusion. The overall remission rate and complete remission rate of anakinra in AoSD patients were 81.66% (95% CI: 69.51%–89.69%) and 66.75% (95% CI: 59.94%–75.3%), respectively. Compared with the controls, the use of anakinra was associated with a significant remission in AoSD, with an OR of 0.16 (95% CI: 0.06–0.44, P=0.0005). There were also significant reductions of the dosage of corticosteroid (mean difference =21.19) (95% CI: 13.2–29.18, P