Liver failure associated with benzbromarone:A case report and review of the literature

BACKGROUND Benzbromarone is a uricosuric agent that reduces proximal tubular reabsorption of uric acid.Because of hepatotoxicity,it has been withdrawn from the market in Europe.Recently,some benefit-risk assessments of benzbromarone suggest that benzbromarone has greater benefits than risks,and the application of benzbromarone in the treatment of gout and hyperuricemia is still under debate.CASE S UMMARY A 39-year-old man was admitted to the hospital for icterus and nausea,and he was treated with benzbromarone(100 mg/d)for 4 mo because of hyperuricemia He had a 10-year history of beer drinking(alcohol:about 28 g/d).Laboratory data showed severe liver injury and serious coagulation dysfunction;tests for autoimmune antibodies,viral hepatitis,and human immunodeficiency virus were negative.Despite administration of liver function-protecting drugs and efficient supportive treatment,the patient deteriorated quickly after hospitalization and developed grade Ⅱ encephalopathy within a few days.The patient accepted continuous plasma exchange six times;however,his condition did not improve.Based on suggestions from multidisciplinary consultation,the patient underwent liver transplantation 26 d after admission.Liver specimen pathology results showed massive necrosis consistent with drug-induced liver injury,supporting the diagnosis of acute liver failure associated with benzbromarone.The patient recovered quickly thereafter.CONCL USION This case highlights that clinicians should be on the alert for the severe hepatotoxicity of benzbromarone.Before prescribing benzbromarone,physicians should evaluate the high-risk factors that may lead to liver injury and provide suggestions for monitoring benzbromarone’s hepatotoxicity during treatment.

Isolated elevated aspartate aminotransferase in an asymptomatic woman due to macro-aspartate aminotransferase: A case report

BACKGROUND Macro-aspartate aminotransferase(AST), a macroenzyme, is a high-molecular mass complex formed by self-polymerization or association with other serum components that are difficult for the kidney to clear, leading to the isolated elevation of serum AST activity. Cases of macro-AST formation are rare, with only 3 published in the English language literature up to September 2019 in China. In this paper, we present a case in which an asymptomatic woman with persistent isolated elevated AST was confirmed as having macro-AST by the polyethylene glycol precipitation method.CASE SUMMARY A 34-year-old woman was referred to our clinic for elevated AST levels with normal levels of other liver-associated enzymes on November 12, 2018. Her AST level of liver function test had been abnormal for 7 mo before she came to the clinic. The patient was asymptomatic with a normal physical examination. There was no relevant family history and no alcohol consumption or smoking. She had a several-month history of traditional Chinese medical taking and had stopped it 1 year prior. The laboratory tests in our clinic showed only the elevation of AST(89.5 U/L) with no other significant abnormalities. We performed the precipitation technique with polyethylene glycol to confirm the presence of macro-AST. Then for almost a year, her AST level still fluctuated in the abnormal range.CONCLUSION This case highlights that clinical physicians should be familiar with this rare condition of persistent isolated AST elevation due to the presence of macro-AST to avoid unnecessary investigation and patient anxiety.

Evaluation Procedure for Quality Consistency of Generic Nifedipine Extended-Release Tablets Based on the Impurity Profile

A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic factories of China were used to evaluate the uniformity with the original drug in the study. The procedure includes: choice of chromatographic methods, data collection and conformity test, evaluation of intra-batch similarity of drugs, evaluation of generic drugs with the original drug and weighted similarity evaluation of generic drugs. The data were collected via high-performance liquid chromatography (HPLC), and then calculated by correlation coefficient, cosine, principal component analysis (PCA) and hierarchical clustering analysis (HCA). It is more suitable to use peak areas as the vector when calculating the similarity of impurity profile. After weighting the peak areas of the unspecified impurities in further evaluation of the generic quality, the generic level of different factories was differentiated and the best generic factory was picked out.

Mixed neuroendocrine carcinoma of the gastric stump: A case report

BACKGROUND Gastric stump cancer,also known as gastric remnant cancer(GRC),is one of the main complications of postgastrectomy syndrome,which usually occurs following Billroth II reconstruction.The predominant histological subtype of GRC is adenocarcinoma,whereas neuroendocrine carcinoma is relatively rare.In particular,there are few recently reported cases of mixed neuroendocrine carcinoma(MNEC)in the English literature.Here,we present an extremely rare case of MNEC of the gastric stump.CASE SUMMARY A 59-year-old patient presented to our department owing to chronic constipation.He had undergone subtotal gastric resection 35 years prior to admission because of benign peptic ulcer.After admission,the patient underwent several tests,and gastroendoscopy showed evidence of Billroth II gastrectomy and local thickening of the gastric stump mucosa at the gastrojejunostomy site,with bile reflux;pathological biopsy revealed adenocarcinoma.He was then diagnosed with GRC and underwent total gastrectomy,D2 Lymphadenectomy,and esophagojejunal Roux-en-Y reconstruction.Histopathological examination of the specimen identified MNEC comprising MNEC(60%),adenocarcinoma(30%),and squamous cell carcinoma(10%).Postoperative adjuvant chemotherapy was initiated on September 17,2020.Taxol plus cisplatin was administered for only one cycle because of severe liver function damage,and the regimen was changed to etoposide plus cisplatin on October 10,2020 for five cycles.The patient recovered,with no recurrence after 6 mo of follow-up.CONCLUSION Gastric MNECs(GMNECs)is a rare type of GRC.This study presented the unusual occurrence of GMNEC in the gastric stump.This case will contribute to improvements in our understanding of the carcinogenesis,biology,pathology,and behavior of GMNEC and GRC.

ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population

BACKGROUND Schizophrenia(SCZ)is a complex disease which can be affected by both genetic and environmental factors.Prenatal famine exposure may cause changes in DNA methylation levels of genes.Meanwhile,maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ.DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ,and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine.AIM To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.METHODS A total of 954 Han Chinese from Northeast China were recruited,including 443 patients with SCZ and 511 healthy controls.The participants were further divided into famine(born in 1960-1962)and non-famine(born in 1963-1965)groups to investigate the effect of prenatal famine exposure.Four single-nucleotide polymorphisms(SNPs)selected according to the relevant literature were genotyped,namely,rs11917047 in PTPRG,rs2239681 in IGF2,rs3842756 in INSIGF,and rs61955196 in ABCB9.DNA were extracted from peripheral blood samples,and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique.The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine,and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction(GMDR)software.RESULTS Based on the sequencing data,genotype distributions and allele frequencies of the four selected SNPs were determined.All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium(P>0.05).Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model[odds ratio(OR):1.22;95%confidence interval(CI):1.01-1.48;P=0.040].We also found that the rs61955196 allele was related with an enhanced risk of SCZ(G>C,OR:1.22;95%CI:1.01-1.47;P=0.042).However,no associations were observed between rs11917047,rs2239681,or rs3842756 and SCZ risk.Under the optimal genetic model,no significant association of famine with the four SNPs was seen.Though the gene–gene interactions between rs2239681 and rs61955196 were found in GMDR analysis,none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.CONCLUSION Our study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese,providing insight into genetic effects on SCZ.

Bond Order Analysis, Packing Ratio, and Electronic Structures of Two Structural Polymorphs Based on Manganese Complexes

The bond order and packing ratios in the single-crystal of the two structural polymorphs as well as the detailed electronic structures of the molecular model were studied using density functional theory. The strength of different Mn coordination bonds was analyzed in detail through Mayer bond order. Besides bond length, many other factors such as the orientation of ligand and nature of metal also significantly influence the bond order. Packing ratios cal- culated using cluster model reveals that packing along b direction in Dimer is more favorable than other directions due to the associated interactions of π-π and CI…H when packing in this direction. Electronic structure helps ex- plain the formation of Dimer from monomer or direct forming of Chain from ligand/Cl and metal. This would shed light on further understanding the importance of supramolecular interaction on crystal engineering.