Objective To evaluate the effect of CYP3A5 genetic polymorphisms on tacrolimus (Tac) concentration/dosing and other clinical outcomes in a pilot cohort of 113 Chinese HTx recipients.Methods Association between CYP3A5 genetic variants and blood dose-adjusted trough concentrations (C0/D) of Tac at 1st month at the beginning of the immunosuppressive therapy was evaluated in cohorts of 113 patients,then at 1st,3rd,6th,and 12th months after transplantation in 41 patients who received Tac-based immunosuppressive therapy and never changed within one year after transplantation,respectively.In addition,we also evaluated the association between CYP3A5 genetic variants and other clinical outcomes,such as the classifications of endomyocardial biopsy and longterm prognosis.Results The CYP3A5 wild homozygote (* 1/* 1),mutant homozygote (* 3/* 3),and mutant heterozygote (* 1/* 3) occurred in 5,34 and 74 recipients respectively.The gene mutation rate of CYP3A5 in this cohort of Chinese HTx recipients was 80.5 ％ and the homozygous proportion was 65.5％.Compared with CYP3A5 expressors (* 1/* 1 or * 1/* 3),CYP3A5 nonexpressors (* 3/* 3) had a higher Tac C0/D at 1st month (47.34 ± 11.40 vs.116.11 ± 42.40 vs.293.70 ± 171.20,P =0.000),as well as other studied time points (3rd month:98.32 ± 39.43 vs.292.07 ± 141.08,P=0.003;6th month:90.00 ± 21.31 vs.341.68 ± 165.02,P =0.002;and 12th month:96.02 ± 29.33 vs.339.23 ± 162.30,P =0.018);and might have a lower classification of endomyocardial biopsy at 1st month (1.43 ± 0.73 vs.1.50 ± 0.58,P =0.867),3rd month (1.55 ±1.00 vs.2.00 ± 1.73,P =0.512),and 6th month (1.36 ± 0.84 vs.2.33 ± 1.53,P =0.132);as well as a higher mortality due to acute organ rejection (10％ vs.0,P =0.244) and all-cause mortality (20％ vs.9.7％,P =0.580).Conclusion In Chinese HTx recipients,the frequency of this * 3 allele is lower than that has been reported in the white population.The determinations of CYP3A5 genetypes in heart transplant recipients are helpful to guide the individualized Tac regimens.

Objective To investigate the risk factors of severe hemolysis during extracorporeal membrane oxygenation (ECMO). Methods The clinical data of adult patients undergoing ECMO after cardiac surgery admitted to Fuwai Hospital from December 2010 to October 2015 were retrospectively analyzed. Demographic characteristics, renal function, primary disease, operation data, ECMO related data and outcomes were recorded. Patients were divided into normal free hemoglobin (FHB) group (FHB ≤ 500 mg/L) and severe hemolysis group (FHB > 500 mg/L) according to the FHB level during ECMO support. The parameters before and after ECMO support were compared between the two groups. Logistic regression was used to identify the independent risk factors of severe hemolysis. Results A total of 81 patients including 19 patients with severe hemolysis was enrolled, and 62 in normal FHB group. There was no difference in cardiopulmonary bypass (CPB) time, clamping time, lactate level before ECMO, cardiopulmonary resuscitation, intra-aortic balloon pump use and central catheter insertion between two groups. The maximums of serum creatinine (SCr) and FHB levels were higher in severe hemolysis group as compared with those in normal FHB group [maximal SCr (μmol/L): 281.02±164.11 vs. 196.67±87.31, maximal FHB (mg/L): 600 (600, 700) vs. 200 (100, 300)], the incidence of clots in circuit or oxygenator, infection, and hemofiltration in severe hemolysis group was increased [26.3% (5/19) vs. 4.8% (3/62), 31.6% (6/19) vs. 12.9% (8/62), 36.8% (7/19) vs. 14.5% (9/62), all P < 0.1]. As well as outcomes including the rate of site of surgery or intubation bleeding and acute renal failure [ARF, 57.9 % (11/19) vs. 30.6% (19/62), 94.7% (18/19) vs. 41.9% (26/62)], and the survival rate was lowered [10.5% (2/19) vs. 51.6% (32/62), all P < 0.05]. As result of univariate analysis, clots in circuit or oxygenator, infection and hemofiltration were associated with severe hemolysis. It was showed by logistic regression analysis that the clots in circuit or oxygenator was a risk factor of severe hemolysis during ECMO [odds ratio (OR) = 6.262, 95% confidence interval (95%CI) = 1.244-31.515, P = 0.026]. Conclusions The clots in circuit or oxygenator were independent risk factors of severe hemolysis during ECMO. Severe hemolysis can induce the increase of the rate of bleeding in the operation site or intubation and the rate of ARF, and decrease of the survival rate.

Objective:To retrospectively analyze the data of patients undergoing extracorporeal membrane oxygenation (ECMO) during perioperative period of cardiac transplantation and provide objective and reliable evidence for further clinical promotion.Methods:Collect the clinical data of patients undergoing heart transplantation and ECMO support in Fuwai Hospital, analyze the duration of ECMO support, combined use of aortic balloon counterpulsation (IABP), and complications during the supporting period. All statistical analyses were processed by SPSS 23.0 software. Independent sample Student's test was employed for normal distribution and Mann-Whitney U test for abormal distribution. χ2 or Fisher exact test was utilized for comparinge the classification data between groups. Results:All ECMO support models were intravenous-arterial ECMO (V-A ECMO). Eight patients successfully bridging heart transplantation through VA-ECMO. Sixty-one patients (89.7%) who had undergone cardiac transplantation were successfully weaned from ECMO while 48 patients (70.5%) survived and discharged. The most common complications during circulation support are bleeding, acute renal insufficiency, and pulmonary infection. Patients with ECMO support in the operating room had a better rate of survival and weaning off(95.6%, 84.4%) than those with ECMO at the bedside of ICU(72.2%, 27.8%).Conclusions:ECMO can provide adequate circulation and respiratory function support for heart transplant patients, and it is an indispensable treatment for patients to go through the perioperative period of heart transplant surgery smoothly. It is advocated to use IABP combined with ECMO in the early stage and at the same time to increase the perfusion of vital organs, improve the prognosis of patients and obtain good outcomes.

Purpose: Inflammatory cytokines are thought to be involved in the pathogenesis of intracranial aneurysm (IA), although resultsamong studies in the literature are inconsistent. This article sought to review studies on the associations among polymorphismsin inflammatory cytokine genes and IA risk and to provide recommendations for future research. Materials and Methods: A systematic search of PubMed, Embase, and Web of Science was conducted up to August 4, 2019. Theassociations between polymorphisms of inflammatory cytokine genes and IA risk were estimated by pooled odds ratios (ORs) and95% confidence intervals (CIs). Subgroup analyses were performed according to race. Qualitative systematic review was conductedfor variants that were studied in only one study. All analyses were performed using STATA 12.0. Results: 13 studies investigating the associations between polymorphisms in five inflammatory cytokine genes (TNF-α, IL-1α, IL-1β, IL6, and IL-12B) and IA were reviewed. Combined results showed that the A allele of TNF-α rs1800629 polymorphism has aprotective effect against IA (dominant model: OR=0.65, 95% CI=0.47–0.89, p=0.007). No associations were identified between polymorphismsin IL-1α rs1800587, IL-1β rs16944, IL6 rs1800795 and rs1800796, or IL-12B rs3212227 and IA risk. Conclusion This review demonstrated an association between TNF-α rs1800629 polymorphism and IA in Caucasians, illustratingthe potentially important role of genes involved in inflammation in IA.

Objective:The study aimed to study the efficacy and safety of combined dual therapy using anti-programmed death (PD)-1 and tyrosine kinase inhibitor (TKI) with combined triple therapy using anti-PD-1, TKI and locoregional intervention triple therapy in patients with postoperative refractory recurrent liver cancer.Methods:Patients with postoperative refractory recurrent liver cancer who had undergone either anti-PD-1 and TKI dual therapy or anti-PD-1, TKI and locoregional intervention triple therapy between July 2016 and March 2019 at the First Medical Center, Chinese PLA General Hospital were retrospectively studied. Tumor responses were assessed by the modified response evaluation criteria in solid tumors and overall survival and progression free survival were compared. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events.Results:Of 63 patients who were included in this study, there were 25 patients in the dual therapy group (16 males and 9 females, aged 54.3±8.8 years) and 38 patients in the triple therapy group (31 males and 7 females, aged 55.5±8.4 years). The 1-year survival rate of the triple therapy group was significantly higher than the dual therapy group (94.5%vs 54.9%) ( P<0.01). The disease control rate was 64.0% (16/25) in the dual therapy group and 84.2% (32/38) in the triple therapy group, and the difference was not significant ( P>0.05). The incidence of treatment-related adverse events in the triple therapy group and the dual therapy group were 78.9% (30/38) and 80% (20/25), respectively. There was no treatment-related death in the 2 groups. Conclusions:Anti-PD-1 and TKI dual therapy and anti-PD-1, TKI and locoregional intervention triple therapy were effective and tolerable treatments for postoperative refractory recurrent liver cancer. The latter treatment had a significantly better clinical benefit on survival outcomes.

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

Laparoscopic ultrasound (LUS) has the advantage of high resolution,multi-angle exploration,and is widely used in minimally invasive surgery of biliary tract.LUS has a series of auxiliary function in difficult laparoscopic cholecystectomy (LC),common bile duct exploration,surgery of intrahepatic biliary calculi,and intraoperative staging of pancreato-biliary tumor.This paper summarizes the application of LUS in laparoscopic biliary surgeries and the related technical essentials.

PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.
Asian Continental Ancestry Group ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Intracranial Aneurysm ; Logistic Models ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Population Characteristics