Updated Genetic Testing of Primary Hyperoxaluria Type 1 in a Chinese Population:Results from a Single Center Study and a Systematic Review

Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.

Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation

Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor recurrence.To improve the prognosis of HCC patients after LT,we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.Methods:In total,data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis.The patients were divided into the following three groups:Group 1,within the Milan and Hangzhou criteria(n=51);Group 2,beyond the Milan but within the Hangzhou criteria(n=36);and Group 3,beyond the Milan and Hangzhou criteria(n=112).Survival probabilities for the three groups were calculated using multivariate Cox regression analysis.The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis.Results:Child-Pugh stage C and hepatitis B virus(HBV)infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria.The overall survival rates of the 199 patients showed statistically significant differences among the three groups(P<0.001).Moreover,no significant difference was noted in the survival rate between Group 1 and Group 2(P>0.05).Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria(OR=0.478;95%CI:0.308–0.741;P=0.001).Conclusions:Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT.The Hangzhou criteria were effective and analogous compared with the Milan criteria.Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation:A Retrospective Study

Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.