[Summary] Dyslipidemia after organ transplantation is one of the important risk factors of postoperative cardiovascular disease and graft dysfunction. There are many factors that result in postoperative dyslipidemia. However, the factors influencing serum lipid levels are changing with the development of organ transplantation. In this article the effects of different anti-rejection drugs such as cyclosporine, azathioprine, mycophenolate mofetil, tacrolimus, rapamycin ( sirolimus ) , corticosteroids, and monoclonal antibody on dyslipidemia after organ transplantation were summarized in different eras.

OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics* ; Creatine ; Genetic Testing ; Heterozygote ; Humans ; Mental Retardation, X-Linked ; Mutation

OBJECTIVE: To explore the genetic etiology of a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Prenatal ultrasonography has revealed oligohydramnios and abnormal structure of fetal kidneys. After careful counseling, the couple opted induced abortion. With informed consent, genomic DNA was extracted from the muscle sample of the abortus and peripheral blood samples of the couple. High throughput whole exome sequencing was carried out to detect potential variants in relation with the disease. Suspected variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed increased size of fetal kidneys, with multiple hyperechos from the right kidney, and multiple hyperechos with anechoic masses within the left kidney. DNA sequencing revealed that the fetus has carried heterozygous variants of the PKHD1 gene, including c.7994T>C inherited from its father, and two heterozygous variants of the PKHD1 gene c.5681G>A from its mother. CONCLUSION The compound heterozygous c.7994T>C and c.5681G>A variants of the PKHD1 gene probably underlay the pathogenesis of ARPKD in this fetus. Above results can provide guidance for subsequent pregnancies of the couple.
Female ; Fetus ; Genetic Testing ; Humans ; Mutation ; Polycystic Kidney, Autosomal Recessive/genetics* ; Pregnancy ; Receptors, Cell Surface/genetics*

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the liver, which with high malignancy and poor long-term prognosis. Radical resection is the only effective treatment for intrahepatic cholangiocarcinoma. In recent years, with the deepening understanding of the biological behavior and clinical characteristics of intrahepatic cholangiocarcinoma, its clinical stage, surgical indications, surgical methods, lymph node dissection and other surgical treatment strategies have also changed. This article reviews the current status of surgical treatment of intrahepatic cholangiocarcinoma based on the latest clinical research progress.

Portal vein thrombosis is one of the common complications of liver cirrhosis. The incidence of portal vein thrombosis is increased with the progression of diseases. The incidence and progression of portal vein thrombosis are associated with multiple factors. The indications of anticoagulant therapy remain to be investigated. At present, portal vein thrombosis is no longer considered as a contraindication for liver transplantation. Nevertheless, complicated portal vein thrombosis will increase perioperative risk of liver transplantation. How to restore the blood flow of portal vein system is a challenge for surgical decision-making in clinical practice. Rational preoperative typing, surgical planning and portal vein reconstruction are the keys to ensure favorable long-term prognosis of liver transplant recipients. In this article, epidemiological status, risk factors, typing and identification of portal vein thrombosis, preoperative and intraoperative management of portal vein thrombosis in liver transplantation, and the impact of portal vein thrombosis on the outcomes of liver transplantation were reviewed, aiming to provide reference for perioperative management of portal vein thrombosis throughout liver transplantation.

Objective: To evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A study was conducted on 25 patients consisting of 10 males and 15 females with CTEPH who received BPA treatment from February 2017 to May 2018 in Beijing Chaoyang Hospital, Capital Medical University. The changes of brain natriuretic peptide (BNP), mean pulmonary artery pressure (mPAP), tricuspid annulus systolic plane excursion (TAPSE), six-minute walking test (6WMD), right ventricular basement diameter and WHO cardiac function grading were compared before and after treatment with BPA using paired t test. Results: Twenty-five patients received a total of 50 BPA treatments, and among them, 12 patients received two or more times. The mPAP decreased from (50.4±9.9) mmHg (1 mmHg=0.133 kPa) to (39.9±10.6) mmHg before and after operation, and the difference was statistically significant (t=9.7, P<0.001); BNP decreased from (513.5±357.3) pg/ml to (106.3±137.53) pg/ml, and the difference was significant (t=3.2, P=0.006); TAPSE increased from (16.2±2.8) mm to (18.0±2.4) mm, and the difference was statistically significant (t=-5.7, P=0.002); the right ventricular base diameter decreased from (45.9±6.9) mm to (41.2±7.3) mm, and the difference was statistically significant (t=5.6, P<0.001); 6WMD increased from (371.1±86.8) m to (467.7±76.1) m, with statistical significance (t=-6.4, P<0.001); WHO cardiac function grading was improved from (2.4±0.7) to (1.2±0.4) after surgery, and the difference was statistically significant (t=2.8, P=0.021). Pulmonary artery injury occurred in 3 patients and 2 patients had hemoptysis.The hemoptysis was stopped after arterial embolization. No other complications such as pulmonary edema occurred. Conclusion BPA may improve clinical status and hemodynamics of patients with CTEPH, which offers an alternative approach of treatment in patients with inoperable CTEPH.

OBJECTIVETo study the difference of microRNA (miRNA) expression between two groups of early stage (pT1N0) esophageal squamous cell carcinoma (ESCC) patients who had different outcome and the prognostic significance of different miRNA in metastatic of early ESCC, and to identify useful prognostic markers in the selection of appropriate treatment for early ESCC patients.

METHODSTaqMan human miRNA arrays and bioinformatics were used to detect and analyze the expression profiles of miRNAs in the two groups, and RT-PCR was used to verify the differences in miRNA expression.

RESULTSThe miRNA arrays revealed a total of 41 markedly changed miRNAs in the survival group compared with the death group. Bioinformatics analysis, prediction and significant function analyses of targeted genes and pathway analysis identified that miR-27a, miR-143 and miR-886-5p levels were increased or decreased by seven-folds or more. The enriched target genes were GRB2, SOS1, MAPK1, EGFR, CBL, SPRY2, RPS6KA5, IGF1R, NGFR, MAPK14 and CREB1. These genes were significantly related to the following signaling pathways, i.e.Sprouty regulation of tyrosine kinase signals pathway, Erk1/Erk2 Mapk signaling pathway and transcription factor CREB and its extracellular signals.

CONCLUSIONSmiR-27a, miR-886-5p, and miR-143 may be potential prognostic markers of metastasis for early ESCC. The detection of these miRNAs plays a directive role for the treatment options of early ESCC. The regulation of targeted genes and mechanism remain to be further studied.

Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Squamous Cell ; genetics ; pathology ; surgery ; Esophageal Neoplasms ; genetics ; pathology ; surgery ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MicroRNAs ; metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Signal Transduction

Objective: To analyze the application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma. Methods: The clinical data of 33 patients with vascular invasion of pancreatic carcinoma who underwent radical resection from April 2013 to April 2017 in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital were retrospectively analyzed. There were 14 males and 19 females with age of (62.5±10.6)years(ranging from 35 to 78 years). Vascular replacement technique with allogenic blood vessel was used on all patients who underwent radical resection for pancreatic carcinoma. The operation procedure was made according to the specific location of the carcinoma, and the allogenic blood vessel was selected according to the type of vascular invasion. The matching vessel was selected for replacement to the patient who was invaded only one vessel. And the "Y" type of iliac vein was selected for replacement to the patient who was invaded the confluence of portal vein, splenic vein and superior mesenteric vein. After the operation, the patients were followed up by telephone and outpatient review. Results: All of 33 patients were successfully completed the operations. There were 28 patients underwent pancreaticoduodenectomy with vascular replacement, and 5 patients underwent total pancreatectomy with vascular replacement. All the patients were confirmed pancreatic carcinoma and R0 resection according to the postoperative pathology. There were 16 patients with the carcinoma invasion the confluence of portal vein, splenic vein and superior mesenteric vein, 12 patients with the carcinoma invasion the superior mesenteric vein, and 5 patients with the carcinoma invasion the portal vein. There was no perioperative death in this group and no complications related to allogenic blood vessel. The incidence of postoperative complications was 18.2% (6/33), and the incidence of pancreatic fistula was 6.1% (2/33), all of which were biochemical fistula. There were 32 patients were followed up, and the follow-up rate was 96.9%. The median survival time was 14.6 months. The half-year, 1-year and 2-year survival rates were 75.6%, 37.6% and 27.4%. Conclusion The application of vascular replacement technique with allogenic blood vessel for pancreatic carcinoma has a great significance for improving the R0 resection rate and the prognosis of patients.

Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P < 0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P > 0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the short-term group were significantly higher than those in the operative control group (both P < 0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P < 0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (all P < 0.05). The expression level of IL-17A in the immune tolerance group was significantly higher than that in the operative control group (P < 0.05). In the immune tolerance group, the expression levels of IL-10and IL-12p were significantly higher than those in the operative control group (both P < 0.05). The expression level of TGF-β in the short-term group was significantly higher than that in the operative control group (P < 0.05). Compared with the operative control group, the expression levels of intercellular adhesion molecule (ICAM)-1, pro-platelet basic protein (Ppbp), Neuropilin-2, Notch-2 protein in the short-term group were significantly up-regulated (all P < 0.05). The expression levels of CXC chemokine ligand 17 (CXCL17), ICAM-1 and Neuroleptin-2 protein were markedly up-regulated (all P < 0.05), whereas that of B7-1 protein was significantly down-regulated (P < 0.05) in the immune tolerance group. Conclusions Treg cytokines (IL-10, TGF-β and IL-12p), IL-6, IL-17 and trans-membrane signaling pathway molecules (ICAM-1, Neuropilin-2, B7-1 proteins) play a pivotal role in the natural immune tolerance process of rat models of liver transplantation.

Objective To investigate the guiding role of quantitative evaluation system of immune status in the individualized management of immunosuppressants for the recipients after liver transplantation. Methods Clinical data of 239 liver transplant recipients were retrospectively analyzed. MingDao Immune Cell Analysis (MICA) was established. All recipients were divided into two groups according to the adjustment regimens of immunosuppressants. The immunosuppressant regimen was adjusted according to MingDao Immune System Score (MISS) in the MISS group (n=84), and the medication plan was empirically adjusted during the same period in the control group (n=155). According to the time of postoperative detection (t), the recipients in the MISS group were divided into subgroup A (t ≤ 28 d, n=78), subgroup B (28 d < t ≤ 6 months, n=68), subgroup C (6 months < t ≤ 12 months, n=18), subgroup D (12 months < t ≤ 24 months, n=18) and subgroup E (t > 24 months, n=19). In the MISS group, postoperative MISS scores of recipients in subgroups A-E were analyzed. The incidence of acute rejection and opportunistic infection and the overall survival rate were statistically compared between the MISS and control groups. Results The MISS scores in subgroups A-E were -7.0 (-13.2, -2.0), -2.0 (-5.8, 1.8), -0.5 (-7.3, 2.8), -2.0 (-4.5, 3.3) and -3.0 (-6.0, 1.0), respectively. The immune status of the recipients was gradually improved over postoperative time, and the difference between two groups was statistically significant (P < 0.05). In the MISS group, 15% (13/84) of the recipients developed acute rejection, and 27% (42/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the MISS score of the recipients with acute rejection was 0 (-2.5, 3.5), and -5.0 (-12.0, -1.0) for their counterparts without acute rejection, and the difference was statistically significant (P < 0.05). In the MISS group, 2% (2/84) of the recipients presented with postoperative opportunistic infection, and 9% (14/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the 1- and 3-year overall survival rates were 86.9% and 79.8%, and 83.2% and 76.8% in the control group, and no significant difference was observed between two groups (P > 0.05). Conclusions MICA and MISS score may reflect the immune status of liver transplant recipients, and guide the individualized management of administration of immunosuppressants after liver transplantation.