Associations of POR*28 polymorphisms with tacrolimus stable dose in Chinese kidney transplantation patients / 中国临床药理学与治疗学

AIM: To investigate the correlation between POR*28 single nucleotide polymorphism (SNP) and tacrolimus stable dose in Chinese kidney transplant patients, and to provide reference for the development of individualized dose adjustment programs in this population. METHODS: A total of 350 Chinese kidney transplant patients were enrolled. CYP3A5*3 and POR*28 genes were detected by Mass ARRAY Analyzer Compac Mass spectrometry in Shenggong Bioengineering (Shanghai) Co., LTD. Serum trough concentration of tacrolimus was determined by ENZYME amplification immunoassay (EMIT). The correlation between the above genotypes and tacrolimus stable dose was analyzed. RESULTS: The frequencies of CYP3A5*3 and POR*28 alleles were consistent with hardy-Weinberg genetic balance. The stable dose in patients with CYP3A5*3 GG genotype was significantly lower than that in patients with AG and AA genotype. Based on stratified analysis of CYP3A5, different POR genotypes were significantly correlated with the stable dose of tacrolimus in CYP3A5 expression and non-expression groups. The mean stable dose of tacrolimus was statistically significant between POR*28 patients with at least one T allele and CC wild-type patients (P = 0.003 7 and P = 0.003 1). Multiple Regression Analysis showed that CYP3A5*3 and POR*28 explained 36.6% and 1.7% of the individual differences in stable doses of Tacrolimus, respectively. CONCLUSION: CYP3A5 *3 and POR*28 genotypes are significantly correlated with tacrolimus stable dose in Chinese kidney transplant recipients, and detection before transplantation will contribute to clinical individualized tacrolimus medication.

Screening of Botanical Drugs against SARS-CoV-2 Entry

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19.

Percutaneous closure of residual shunting in a patient with a fenestrated atrial septal defect occluder: A case report.

RATIONALE: Fenestrated atrial septal defect (ASD) occlusion has been performed in patients complicated with severe pulmonary hypertension (PH). Nevertheless, the persistent interatrial residual shunting in the fenestration might increase the risk of paradoxical embolism. Percutaneous closure of fenestrated ASD occluder (ASO) has not yet been reported. PATIENT CONCERNS: A 26-year-old patient with a 25-mm ASD and severe PH underwent ASD closure using a Memory ASO with a waist of 32 and 6-mm custom-made fenestration. Echocardiography revealed the fenestration remained 6 mm and the pulmonary artery pressure decreased to the normal range at the 6-month follow-up. DIAGNOSES: Persistent interatrial residual shunting in ASO. INTERVENTIONS: Percutaneous closure of residual interatrial shunting was performed using a waist of 8-mm ASO under guidance of TEE. OUTCOMES: The fenestration was successfully closed. Neither thromboembolism nor infection events were noted during the 12-month follow-up after the procedure. LESSONS: This case illustrates that percutaneous closure of the residual shunting in fenestrated ASO was feasible and safe for short- and long-term.

Advance in research on pharmacogenomics of vitamin / 中国药理学通报

Vitamin is necessary and important for humans and an-imals to maintain normal physiological function, metabolism, and growth. The studies suggest that vitamin is one of the factors which play a role in the activity of enzymes, and it is coenzyme of many enzyme or an important component of coenzyme. The lack of vitamins causes a metabolic vitamin deficiency. Pharma-cogenomics research the relationship between human genetic vari-ation and drug reaction, using the information to solve the differ-ent reactions among the different individuals of the same drug. Vitamins, which constitute human tissues and maintain normal physiological functions, are also an important part for the phar-macogenomics study.

Off-pump occlusion of trans-thoracic minimal invasive surgery on simple congenital heart diseases / 中华胸心血管外科杂志

ObjectiveReport an operation of off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) adopted on the therapy of 92 patients suffered with simple congenital heart diseases (CHD) of atrial septal defect ( ASD),ventricular septal defect ( VSD ) and patent ductus arteriosus (PDA) and summarize the experiences.Methods The clinical data of 92 CHD patients administrated with OPOTTMIS in our hospital during the time of July 2008 and July 2011 were analyzed retrospectively.Moreover,the relevant literatures were reviewed and the different kinds of treatments and their outcomes of CHD were compared.These patients were 3-56 years old and weighed 8.0-54.5 kg,with male and female 38 and 54 cases,including ASD 52 cases,VSD 26 cases and PDA 14 cases,respectively.Within the initial 3 months of postoperation,all the patients were followed up and managed to take the re-examination with electrocardiogram and echocardiogram one time for each month,and 3 months later,at least one time for every 3-6 months.Results91 cases were performed the OPTTMIS procedure successfully,1 child with sieve-like ASD transferred to open-heart surgery and 1 adult( 1.1％ ) PDA died on the second day after operation for the pulmonary hypertension crisis.4 cases appeared mild residual shunt including 2 of ASD,1 of VSD and 1 of PDA.2 cases showed Ⅱ stage atrial ventricular block ( AVB ) within ASD and VSD,respectively.Also,post-operation hemothorax happened to 1 case ASD and 1 case VSD for the active bleeding of cardiac puncture site and the exploration and hemostatic operation were performed.91 (98.9％) patients were performed the OPOTTMIS operation successfully,the total complications within 72 hours was 6.5％ (6/92),respectively.There were no heavy complications happened during peri-operation such as cardiac rupture,infective endocarditis,stroke,hemolytic and thrombus formation.90 patients outcomes of 3 months to 4 years follow-up with the ECG and UCG examination showed that there were no Ⅲ stage atrioventricular block,no obvious occluder shift and broken and no moderate cardiac valve regurgitation,no evident blood flow restriction of left ventricular outflow tract and descending aorta,only found mild residual shunt within 2 cases ( VSD and PDA each) and heart expansion compared to pre-operation within 2 PDA patients.However,all the patients'heart functions were in grade Ⅰ to grade Ⅱ according to NYHA standard.ConclusionOPOTTMIS is a safe,feasible and effective option on simple congenital heart diseases.