Primary hyperoxaluria(PH)is a rare autosomal recessive disorder,with PH type 1(PH1)being the most common.It is primarily characterized by recurrent renal calculi,renal calcification,and can lead to acute renal failure.In infants,PH1 often results in early end-stage renal disease(ESRD)with a high mortality rate.This paper reports a case of an infant with acute renal failure in the Second Hospital of Shandong University who was diagnosed as PH1 using whole-exome sequencing,revealing a homozygous mutation in the AGXT gene(c.596-2A＞G),which is reported here for the first time in the Chinese population.Previous literature indicates that urinary oxalate levels and stone composition can suggest PH1,with the gold standard for diagnosis being liver biopsy combined with alanine-glyoxylate aminotransferase(AGT)enzyme activity assessment.However,due to its convenience,AGXT gene sequencing has increasingly become the preferred diagnostic method.Conservative treatments for PH1 include adequate fluid intake,citrate,vitamin B6,and continuous renal replacement therapy,while liver transplantation is the only curative treatment.Infants with unexplained acute renal failure should be evaluated for PH1,with early detection of the level of urine oxalate and screening for genetic testing recommended.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective: To explore the relationship between high sensitivity C-reactive protein (hs-CRP) and vascular access failure in hemodialysis patients. Methods: From July 2017 to June 2018, 105 patients with regular hemodialysis were selected from the blood purification center of Beijing Haidian hospital.According to the presence or absence of VAF, the patients were divided into two groups: VAF+ group and VAF - group.The difference of hs CRP level between the two groups was compared. Results: During the 12-month follow-up, 17 patients had more than one event of vascular failure.The total protein level of VAF+ group was significantly lower than that of VAF-Group((65.61±4.01) g/L and( 68.98±5.66) g/L, P=0.021). The male proportion of VAF+ group was lower than that of VAF-group (29.41% vs 53.41%, P=0.07), but the difference was not statistically significant.There was no significant difference in the annual change level of hs CRP between VAF + group and VAF Group((0.33±5.49) mg/L and(0.57±4.45) mg/L, P=0.840). The level of total protein was the independent protective factor of VAF(OR=0.889, 95%CI 0.797-0.991, P=0.034). The level of hs CRP was not significantly correlated with vascular access events(OR=1.018, 95%CI 0.926-1.119, P=0.713). Conclusion There is no correlation between hs CRP and VAF.The exact mechanism of inflammation in intimal hyperplasia needs further study.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Zinc oxide quantum dots (ZnO QDs) were synthesized by gel-sol method and employed as the transdermal aloesin (Alo) carriers. ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane (APTES). Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs, which were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA). TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution, of which was around 4 nm. The size of Alo NPs increased to around 8 nm due to the surface modification. The intense bands at around 3 400 cm and 1 200 cm in the FTIR spectrum of Alo NPs from the vibration of -OH indicated the linkage of Alo on the surface of ZnO QDs. The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27% and 35.14%, respectively. The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin, which manifested the improvement of the penetration for Alo delivered by ZnO QDs. The pH-controlled drug release behavior was investigated. At pH 7.4, only a small amount of Alo (1.45% ± 0.21%) had been released after 2 h. In contrast, as incubation at pH 5.0 of which pH was similar to endosomal environment, Alo was released very fast (87.63% ± 0.46% in 2 h) from Alo NPs, confirming that Alo NPs could response to the pH and realize the intracellular drug release. The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner. When the concentration of Alo NPs was 12.5 μg/mL, the inhibition rate was up to 40.32% ± 1.57%. All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.
Administration, Cutaneous ; Animals ; Chromones ; administration & dosage ; Drug Delivery Systems ; Glucosides ; administration & dosage ; Guinea Pigs ; Monophenol Monooxygenase ; metabolism ; Nanoparticles ; Quantum Dots ; Zinc Oxide

Objective To evaluate the clinical application of TCM nursing therapies and identify the problems during the therapy implementation, in order to explore the countermeasures to promote its clinical improvement. Methods A descriptive cross-sectional study was conducted,and a self-designed questionnaire was employed to investigate 218 nurses from 148 grade A class three TCM hospitals in China. Results 25 TCM nursing therapies were implemented in these hospitals. Ear acupressure therapy was the most frequently implemented,accounting for 83.5%(182/218);while wax therapy was the least implemented, accounting for 7.8%(17/218). The implementation frequency of these technologies varied significantly, 0~860 times a week. The top three of them were acupoint application therapy, hot compression of Chinese medicine and ear acupoints therapy.TCM nursing therapies were considered to be the most frequently used in insomnia, headache, edema, arthralgia, cold, epigastric pain, hypochondriac pain and fever.Storage of TCM nurses,lacking of TCM knowledge and inapposite therapy implementation were the main problems in the application. Conclusions Scientific and rational allocation of human resources, cultivation of the TCM-specific nursing professional, enhancement of nurses'awareness of Chinese medicine, establishment of a reasonable charging standard, and strengthening the risk management in implementation will promote its clinical development.

Objective To study the cardiac electrophysiology changes of canine asynchrony ischemic heart failure under left ventricular endocardial pacing.Methods Left bundle branch radiofrequency catheter ablation and left anterior descending coronary artery ligation were used to establish the model of ischemic heart failure in 18 healthy dogs.Eighteen healthy dogs were randomly divided into two groups,9 cases in each group.The experimental group was treated with cardiac resynchronization therapy(CRT) in left ventricular endocardium,and the control group underwent the sham operation.ECG and echocardiography were done at 6 weeks after operation.Results The left ventricular ejection fraction in the experimental group was significantly higher than that in the control group(38.32 ± 6.08 vs.30.62 ±8.96).The asynchronization index in the experimental group was significantly lower than that in the control group(35.99 ±5.25 vs.78.21 ± 7.02),and the difference was statistically significant(P＜0.05).QRS(60.58 ± 7.43 vs.68.33 ± 8.01) and QTc(347.09 ± 17.33 vs.367.81 ± 22.02)in the experimental group were significantly shorter than those in the control group(P＜0.05);moreover Tp-e(37.03±9.07 vs.45.76±7.11) and ARI(162.33±22.06 vs.187.21±23.87) in the experimental group were significantly lower than those in the control group(P＜0.05).Conclusion Left ventricular endocardial pacing can produce preferably electrophysiological effects and achieve the goal of effective cardiac resynchronization therapy.

Objective To explore the clinical application value for calculating the volume of splenic embolization by splenic artery branch diameter ratio method.Methods Data of 20 patients with cirrhosis and hypersplenism who underwent partial operation of splenic artery embolization were retrospectively analyzed.Based on the angiography of splenic artery during operation,the diameter of branch vessels of splenic artery was measured and the percentage of embolism volume in spleen was calculated.CT scans were performed on all patients after one month of the operations.Based on VR reconstruction image,the percentage of embolism volume in the spleen was calculated.Postoperative complications and adverse responses were observed.Peripheral blood red cells,white blood cells and platelets were tested repetitively three days before the operation,and a week,a month,three months after the operation.Moreover,the statistical analysis was performed.Results The difference between the percentage of embolism volume in the spleen calculated by splenic artery branch diameter ratio method ([52.15±3.29]％) and calculated by CT ([49.99±6.02]％) was not statistical (t=-1.630,P=0.120).All the patients had moderate or below moderate pain on left upper quadrant,and had symptoms of nausea,vomiting and fever after the operation.They all got better after symptomatic treatment.Peripheral blood red cells,white blood cells and platelets all had significant differences among three days before the operation,a week,a month and three months after the operation (all P＜0.001).Conclusion During the partial splenic embolization,the application of ratio method on branch vessels of splenic artery to measure the volume of embolism in the spleen is convenient,prompt and relatively accurate.It is worthy to be expanded in clinic.

Objective To evaluate the feasibilty of modified osteogenic culturing of goat adipose derived stromal cells(ADSCs).Methods From March,2013 to September,2014,platelet-rich plasma(PRP) was made from goat autogenous vein blood,and abodimoneal fat was aspirated,following aspetic procedure,primary and series passage of ADSCs was established.Osteoinduced ADSCs was carried out according to following group:combinative osteoinduction group(PRP+rhBMP-2 +ADSCs),growth factor group(rhBMP-2+ADSCs),conventional inductive group(dexamathasone+ascorbic acid + ADSCs) and noninductive group(blank group).Converted microscope was used to observe cellular pattern,cell activity,osteocalcin and collagen type Ⅰ level were detected at 1,3,5,7,9,13,17,21 days.Red Alazarin and Von Kossa staining were also assayed at different interval.Results Under observation of converted microscopy,remarkable cell proliferation with abundant ECM was noticed in combinative osteoinduction group,compared with other groups,level of cell activity,osteocalcin,collagen type Ⅰ [(0.82 ± 2.19)AU,(79.82 ± 1.36)U/L at,(78.51 ± 4.32)μ g/ml at]were significantly higher than other groups (P ＜0.05),and remarkable ALP expression and calcifed nodules were also seen.Conclusion PRP can enhance the inductive effect of rhBMP-2,and combinative osteoinduction procedure acts as a satisfactory culturing method.