Volume 96  ·  Issue 10  ·  2016

Hepatectomy is still the gold standard in the treatment of liver malignancies, and complete resection of the lesion can provide a chance of cure. Liver metastasis from colorectal cancer is also the most common indication for hepatectomy. Patients with complete resection of these lesions can have a 5-year survival rate of 30% to 40%. However, in practice, most patients with primary or secondary liver malignant tumors are not suitable for hepatectomy, and the efficacy of traditional systemic chemotherapy for these patients is limited. Therefore, the emergence of tumor ablation methods fills the therapeutic gap in patients who are not suitable for hepatectomy^[1,2,3]。 At present, the most commonly used tumor ablation methods in clinical practice should be mainly divided into two categories: chemical ablation and thermal ablation. The application of radiofrequency ablation (RFA), one of thermal ablation, in liver surgery is discussed.

The "13th Five-Year Plan" is a critical period for China to build a moderately prosperous society in an all-round way and a sprint stage for building an innovative country. Carrying out in-depth strategic research and scientifically planning the development of science funds during the 13th Five-Year Plan are of great significance for the prosperity of basic research, the enhancement of China's original innovation ability and the service of innovation-driven development.

To investigate the expressions of nuclear factor-κB (NF-κB) and P-glycoprotein (P-gp) in patients with liver diseases and the effects and mechanism of intervening NF-κB activation on multiple drug resistance (MDR) reversal.

The levels of circulating NF-κB and P-gp expression were quantitatively detected in 294 patients with liver diseases by using enzyme-linked immunosorbent assay. NF-κB gene transcription in human HepG₂ cells was intervened by specific siRNA with/without doxorubicin treatment. Levels of protein or gene expression were analyzed by Western blotting or fluorescence quantitative polymerase chain reaction (PCR).

The dynamic increase of circulating NF-κB and P-gp expressions were observed during patients from chronic hepatitis to cirrhosis to hepatocellular carcinoma (HCC) development. The levels of serum NF-κB and P-gp expression in HCC were significantly higher (P<0.001) than those in cirrhosis, chronic hepatitis, and normal controls. The expression levels of serum NF-κB and P-gp were significantly associated with HBV infection (P<0.05), elevated after interventional chemotherapy with higher frequency or prolonged therapy, and significantly decreased in the post-operative HCC (P<0.001). Both expressions in HepG₂ cells were significantly higher after adding doxorubicin in the cell cultures. After the cells were transfected with siRNA, the NF-κB expression was down-regulated at mRNA or protein level with higher sensitivity to doxorubicin.

The over-expressions of NF-κB and P-gp are closely associated with MDR formation; intervention of NF-κB activation can inhibit P-gp expression, and enhance the sensitivity to anti-cancer drug and reverse MDR of HCC.

To investigate the relationship between the expression of immunoglobulin heavy chain binding proetin(Bip)and calreticulin(CRT) and metastasis in hepatocellular carcinoma.

Western blot and RT-qPCR were used to detect the expression of Bip and CRT in normal hepatic cells and hepatocellular carcinoma cells. 43 cases of hepatocellular carcinoma tissues were collected from the First Affiliated Hospital of Zhengzhou University between June 2014 and May 2015, Western blot and immunohistochemistry assay were used to detect the expression of Bip and CRT in hepatocellular carcinoma tissues, adjacent non-cancer tissues, 5 cases adjacent liver hemangioma tissues and the clinical significance was also analyzed.

The expression of Bip and CRT in hepatocellular carcinoma cells and hepatocellular carcinoma tissues was higher than normal hepatic cells and adjacent non-cancer tissues and also adjacent liver hemangioma tissues. The positive rate of Bip and CRT were 86.0%(37/43) and 65.1%(28/43)in 43 hepatocellular carcinoma tissues, which was significantly higher than those adjacent non-cancer tissues and adjacent liver hemangioma tissues(P<0.05). The positive rate of Bip and CRT in metastatic cancer tissues were 100% (19/19), 84.2%(16/19), respectively, which was significantly higher than those non-metastatic cancer tissues 75.0%(18/24), 50.0%(12/24) respectively (P<0.05). The expression of Bip and CRT was positively correlated(r=0.382, P<0.05). The positive rate and relative expression of Bip were correlated with TNM stage, metastasis in hepatocellular carcinoma tissues(P<0.05), while the positive rate and relative expression of CRT were correlated with metastasis in hepatocellular carcinoma tissues(P<0.05).

The expression of Bip and CRT is correlation with metastasis in hepatocellular carcinoma.

To report five cases of isolated IgG4-related sclerosing cholangitis (IAC) and to summarize their clinical characteristics and the differential diagnosis.

The clinical data of five patients with isolated IAC were retrospectively analyzed, including laboratory tests, imaging examination and liver pathology. Their treatment and prognosis were also discussed.

All five patients had no history of pancreatitis. All five patients presented with jaundice and three of them had fluctuant jaundice. The serum IgG4 levels was increased in all five patients. The images study showed bile duct stenosis in all 5 patients (2 in hilar bile duct, 2 in intrahepatic bile duct and 1 in hilar associated distal bile duct). The enlargement of pancreas was found in 2 patients. Liver pathology revealed fibrosis around small bile duct and IgG4-positive plasma cells infiltration in all 5 patients. Two patients underwent surgical procedure without relief. All five patients were relieved after the treatment of steroid. All patients were followed up from 6 months to 2 years and no recurrence was detected.

Isolated IAC is a rare disease and it could be misdiagnosed as cholangiocarcinoma. The surgical procedure has the limited effect for the treatment of IAC and it should be avoided. IAC should be considered for patients with fluctuant jaundice of long history and enlargement of pancreas on imaging. Serum IgG4 test and liver biopsy are helpful for the diagnosis of IAC.

To develop and evaluate a warfarin-dosing algorithm method which can be used to guide the adjustment of warfarin maintenance dose in Chinese Han population.

A total of 512 patients with steady warfarin taking were recruited from Beijing Hospital during May 2012 to December 2014. Indications for warfarin prescribing included prosthetic heart valve, atrial fibrillation and pulmonary embolism. Genomic DNAs were extracted from blood samples and used for the genetic polymorphism analysis of VKORC1 and CYP2C9 (include ^*3 and ^*13 alleles). Warfarin dose, demographic variabilities and amiodarone compliance were recorded during regular visit. These patients were randomly divided into groups using the method of random number table, 384 patients were randomly selected as derivation group, the remaining 128 cases as the validation group.Using data from derivation group, a warfarin-dosing algorithm was established based on the genetic information, demographic characteristics and concomitant compliance by a multiple linear regression analysis parameter. Then the accuracy of newly developed algorithm method was further evaluated by comparing the predicting dose with the actual dose in the validation group.

The stable dose of warfarin was tightly associated with factors like age, height, weight, VKORC1 -1639G>A,CYP2C9^*3, CYP2C9^*13 and amiodarone usage. Newly developed algorithm method exhibited better prediction effect (R²=0.682, P<0.01) as compared with that of previously reported algorithm methods. The weights ofVKORC1 and CYP2C9 for predicting of warfarin dosage were estimated to more than 50%. Using this method, 62.5% of patients in the validation group could be well recognized, in which the predicting dose of warfarin was within 20% of the actual dose, and only 7.81% patients showed underestimated prediction warfarin dose while 29.69% patients showed overestimated values.

Newly developed algorithm method can be used for the guidance of warfarin maintenance dose adjustment in Chinese Han population.

To find out the factors affecting the outcome of pulmonary-acute respiratory distress syndrome (pARDS) patients treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO).

From November 2009 to April 2014, the clinical data of patients with pARDS supported with VV-ECMO in intensive care unit of China-Japan Friendship Hospital and Chaoyang Hospital were prospectively collected and analyzed. The clinical data included general condition before VV-EMCO, VV-ECMO treatment, ventilator settings of mechanical ventilation and complications during VV-ECMO. All patients were divided into survival group and non-survival group, according to the 28 days' survival situation after VV-ECMO treatment. The clinical data of the two groups before and after VV-ECMO treatment were compared, and the factors affecting outcome of VV-ECMO treatment in the patients with pARDS were analyzed.

A total of twenty-five patients were enrolled in the study, of whom 14 patients survived, 11 patients died.The results showed that the proportion of immunocompromised patients with pARDS in the survival group was lower than that of non-survival group (7.1% vs 45.5%, P=0.026). Before the treatment of VV-ECMO, the duration of mechanical ventilation in the survival group was shorter than that in the non-survival group [25(7, 48) vs 48(21, 120) h, P=0.048], and Murray score was also lower than the non-survival group [3.5(3.3, 4.0) vs 4.0(3.9, 4.0), P=0.020]. During the treatment of VV-ECMO, the duration of ECMO support in the survival group was shorter than that in the non-survival group [7.0(5.0, 9.0) vs 13.0(7.8, 26.0) d, P=0.030], and the proportions of disturbance of blood coagulation and circulatory failure in the survival group were lower than those of non-survival group [0% vs 36.4%, 21.4% vs 63.6%, both P<0.05]. In addition, there were five "awake ECMO" patients during the treatment and all in the survival group.

The immunocompromised condition, pre-ECMO ventilation duration and Murray score are the important factors influencing the outcome of VV-ECMO treatment in the patients with pARDS.

To describe the clinical features of eosinophilic granulomatosis with polyangiitis (EGPA).

Patients who fulfilled the criteria for EGPA managed at the Beijing Chaoyang Hospital of Capital Medical University between May 2005 and Feb 2014 were retrospectively investigated. Patients' characteristics were compared according to antineutrophil cytoplasmic antibody (ANCA) status.Patients were followed up in outpatient service or by telephone to evaluate the treatment result.

There were 43 patients included, 24 males and 19 females. Mean age at onset was (53.0±15.0) years old. The most common onset symptom of EGPA was asthma in 30 (69.8%) patients. Asthma was also the most common symptom in 42 (97.7%) patients, followed by sinusitis and rhinitis in 40(93.0%) patients and peripheral neuropathy in 26 (60.5%) patients. ANCA positive was found in 13 (30.2%) patients, mainly anti-myeloperoxidase antibodies. High resolution computed tomography scanning (HRCT) of the chest was performed in all the patients, and the main anomalies included ground-glass opacities in 34 (79.1%) patients and bronchial wall thickening and/or bronchial dilatation in 22 (51.2%) patients. Pulmonary function tests available at diagnosis in 33 patients mainly demonstrated an obstructive ventilatory defect. There were totally 33 patients who underwent biopsy, 21 (63.6%) patients had histologic findings supporting a diagnosis of EGPA, including eosinophil infiltration in 21 patients, vasculitis in 5 patients, but no granuloma. ANCA-positive patients were more likely to have fever and renal disease, more honeycombing pattern in the HRCT image and more significantly decreased pulmonary diffusion function, while ANCA-negative patients were more likely to have significant obstructive ventilatory defect. 41 patients received oral corticosteroids, among them, 19 patients additionally received immunosuppressants. 35 Patients were followed for a median of 30 (13, 46) months, 3 patients died (mortality 8.57%), among the other 32 patients, asthma was still the most common symptom in 16 (50%) patients at their last visit, and prednisone administration had to be continued for 23 (71.9%) patients.

The clinical manifestations of EGPA may vary widely, and it involves different organs. Physicians should be alert to EGPA when seeing patients with refractory asthma and eosinophilia.

To analyze the clinical manifestations and identify independent diagnostic predictive factors for Crohn's disease (CD) initially diagnosed as appenicitis and treated by surgery.

The medical records of patients diagnosed as acute appendicitis upon admission and treated by surgical operation in the First Affiliated Hospital of Sun Yat-sen University from January 2000 to December 2014 were retrospectively analyzed. Based on postoperative pathological examination and clinical examination results, 28 CD patients were identified(CD group), and for each CD case, 3 controls with confirmed diagnosis of appendicitis were included (appendicitis group, n=84). Clinical manifestations and laboratory examination results of the two groups were analyzed with multivariable Logistic regression to determine independent diagnostic predictive factors for CD initially misdiagnosed as appendicitis.

Altogether 112 patients were enrolled, with a male-to-female ratio of 1.04∶1 (57∶55), and a median age of 36 years. No significant differences were found in gender, age, and body temperature between the CD group and appendicitis group (all P>0.05). In the appendicitis and CD groups, median duration (Q₁-Q₃) of abdominal pain was 24 (14-48) hours vs 216 (96-384) hours, proportion of patients with lower right abdominal pain was 98.8% (83/84) vs 75.0% (21/28), proportion of patients with shifting lower right abdominal pain was 98.8% (83/84) vs 7.1% (2/28), proportion of patients with local lower right peritonitis was 95.2% (80/84) vs 53.6% (15/28), proportion of patients with change of bowel emptying habit or stool consistency was 7.1% (6/84) vs 46.4% (13/28), proportion of patients with history of chronic abdominal pain or diarrhea was 10.7% (9/84) vs 75.0% (21/28), preoperative white blood cell count was (14.08±4.13)×10⁹/L vs (8.00±3.42)×10⁹/L, preoperative neutrophil count was (11.34±4.10)×10⁹/L vs (5.58±3.22)×10⁹/L, preoperative hemoglobin was (139.52±19.90) g/L vs (107.65±21.68) g/L, preoperative red blood cell count was (4.85±0.74)×10¹²/L vs (4.28±0.87)×10¹²/L, and preoperative platelet count was (220.68±74.47)×10⁹/L vs (302.09±71.65)×10⁹/L, all with significant differences (all P<0.05). Multivariable analysis showed that change of bowel emptying habit and stool consistency (OR=36.712, 95%CI: 1.672-806.103, P=0.022), medical history of chronic abdominal pain or diarrhea (OR=60.142, 95%CI: 4.501-803.573, P=0.002), lower preoperative hemoglobin level (OR=0.909, 95%CI: 0.858-0.963, P=0.001), and higher platelet count (OR=1.027, 95%CI: 1.007-1.047, P=0.008)were independent predictive factors for CD.

CD should be considered in cases initially diagnosed as appendicitis with change of bowel emptying habit and stool consistency, medical history of chronic abdominal pain or diarrhea, anemia, and increased platelet count.

To investigate the frequency of and risk factors for re-bleeding in obscure gastrointestinal bleeding (OGIB) patients who had negative findings in capsule endoscopy (CE).

Patients with OGIB referred for CE to the First Affiliated Hospital of Zhengzhou University between January 2011 and December 2012 were identified.Follow-up data were obtained via medical records review, telephone interviews or follow-up clinic visits in order to establish therate of re-bleeding and identify the risk factors associated with re-bleeding among patients with negative CE findings.

A total of 198 patients were included in this study, of whom 196 patients completed the follow-up, with a mean (±SD) follow-up of (16.1±5.3) months. In the 196 patients, 94 had negative CE findings and did not receive any further specific treatment for OGIB. Re-bleeding episodes were observed in 32 of the 94 patients (34.0%), and the cumulative re-bleeding rates at 6, 12, 18, and 24 months in follow-up were 3.2%, 6.4%, 20.2%, 34.0%, respectively. There was no statistically significant difference in re-bleeding rate between patients with positive CE findings and patients with negative CE findings(23.7% vs 34.0%, P=0.246). Diabetes mellitus(HR=3.250, 95%CI: 1.296-8.154, P=0.012), minimum hemoglobin levels ≤80 g/L before CE(HR=0.397, 95%CI: 0.172-0.917, P=0.031), and continued use of aspirin after CE(HR=4.915, 95%CI: 1.887-12.800, P=0.001)were independent risk factors for re-bleeding among OGIB patients with negative CE findings.

Considering the high risk of re-bleeding, close follow-ups are needed for OGIB patients with negative CE findings.Repeated CE or other investigations (enteroscopy and CT enterography)within 12-24 months are recommended for the OGIB patients with negative findings in initial CE investigation who have risk factors for re-bleeding.

To investigate the value of liver to abdominal area ratio (LAAR)in predicting prognosis of alcohol-induced acute-on-chronic liver failure (ACLF).

The clinical data of patients with alcohol-induced ACLF admitted to the First Affiliated Hospital of Fujian Medical University from May 2008 to March 2015 were retrospectively analyzed. The primary outcome was death. The prognosis of the patients in 3 months after admission was followed up. The LAAR upon admission was calculated for each patient. The correlation between calculated liver volume and LAAR was explored. Cox proportional hazards model was used to explore the factors affecting the prognosis of the ACLF patients. Receiver operating characteristic (ROC) curve was drawn to determine the predictive value of LAAR in prognosis of the patients.

Forty-five patients were included in this study, with 43 males and 2 females, and a median age of 48 years.Nineteen patients died with 3 months and 26 patients survived. Liver volume was positively correlated with LAAR(r=0.764, P<0.01). According to Cox analysis, LAAR (OR=1.067, 95% CI: 1.025-1.111, P=0.002) and model for end-stage liver disease (MELD) score (OR=1.103, 95% CI: 1.016-1.197, P=0.019) were independent prognostic factors for 3-months survival of alcohol-induced ACLF patients. The optimal cut-off value of LAAR for predicting survival was 44 (the area under the ROC curve was 0.747, 95% CI: 0.602-0.892, P=0.005).

LAAR could serve as a new prognostic factor in alcohol-induced ACLF patients.

To compare the effectiveness of neostigmine induced reversal of rocuronium in neonates, infants, young children and children.

One hundred and sixty ASA I or Ⅱ pediatric patients undergoings elective surgical procedures under total intravenous anesthesia were enrolled during July 2014 to April 2015 in Tianjin Children's Hospital. The patients were divided into four groups according to ages: neonate group, infant group, young children group and children group.Then control subgroup and neostigmine reversal subgroup including twenty patients were randomly selected from every different age groups by the method of random number table. After induction of anesthesia, 0.6 mg/kg rocuronium was administered, and 0.2 mg/kg maintenance doses given as required during period of operation. Neuromuscular block was monitored using acceleromyographic train of four (TOF). When T₁/control returned to 15%, 0.03 mg/kg neostigmine and 0.01 mg/kg atropine were given to patients of reversal subgroups, and saline 0.1 ml/kg was given to patients of control subgroups. The recovery time of T₂₅, T₇₅, TR_0.7 , recovery index , blood pressure, heart rate and adverse reactions were observed and recorded.

In control subgroups, the recovery time of T₇₅ for neonates , infants, young children and children were (27.10±8.72), (16.70±6.35), (13.05±1.96), (14.40±3.08) min, respectively (F=25.052, P<0.01). The recovery time of TR_0.7 were (27.75±8.56), (18.45±5.62), (14.95±2.64), (15.70±3.36) min, respectively(F=22.496, P<0.01). The recovery index were(20.75±7.09), (12.40±5.04), (10.01±2.00), (10.55±2.82)min, respectively(F=22.725, P<0.01). There were no significant difference for the every recovery time and recovery index between infants, young children and children (allP>0.05) . But the recovery time of T₇₅, TR_0.7 and recovery index in neonate group were longer than other age groups ( all P<0.01). In reversal subgroups , the recovery time of T₇₅ for neonates , infants, young children and children were (14.05±3.54), (8.08±3.08), (6.53±0.98), (7.10±1.54)min, respectively(F=37.947, P<0.01). The recovery time of TR_0.7 were (14.95±3.19), (9.32±3.44), (7.45±1.40), (8.12±1.67)min, respectively(F=34.744, P<0.01). The recovery index were (11.05±3.26), (5.96±2.46), (4.99±0.95), (5.22±1.39)min , respectively(F=33.542, P<0.01). The recovery time of T₇₅, TR_0.7 and recovery index were delayed in neonates compared with other age groups (all P<0.01). Haemodynamics were stable in all groups before or after giving antagonist, and no significant adverse reactions were observed.

The spontaneous recovery time after administrating rocuronium are comparable in infant, young children and children. There are obviously reversal effects in all of age groups when neostigmine is given to antagonize rocuronium. Either spontaneous recovery time or reversal recovery time of neostigmine to rocuronium is longer for neonates than other age's children.

To investigate the effects of a synthetic small double-stranded RNA (dsRNA) dsP21-555 on the development of bladder cancer cell lines T24 and EJ.

According to the different treatments, bladder cancer cells were divided into three groups: negative control group (transfected with dsControl), positive control group (transfected with candidate microRNA, i.e. miR-370) and experimental group (transfected with dsP21-555). Real-time fluorescent quantitative polymerase chain reaction (qPCR) was conducted to detect the expressions of p21 mRNA and cyclin-dependent kinases 4/6 (CDK4/6) mRNA; Western blot was operated to verify the expression of P21 and CDK4/6 proteins. Cell cycle distribution was measured by flow cytometry after transfection. Cell proliferation assay was performed to evaluate the proliferative capacity of transfected cells. Colony formation assay was carried out to analyze the proliferative ability of single cancer cells.

qPCR showed that, compared with the negative control group, dsP21-555 up-regulated the expressions of p21 mRNA by 2.46 times (P<0.01) in T24 cells and 2.60 times (P<0.01) in EJ cells; compared with the positive control group, the expression of p21 mRNA was no significantly different in the experimental group (P>0.05). Compared with the dsControl group, dsP21-555 suppressed the expressions of CDK4 mRNA by 43% (P<0.01) in T24 and 54% (P<0.01) in EJ cells, the expression of CDK6 mRNA by 39% (P<0.01) in T24 and 36% (P<0.01) in EJ cells; the differences in the expression of CDK4 and CDK6 mRNAs between the miR-370 and dsP21-555 groups were not statistically significant (P> 0.05). Western blot verified the differences of p21 and CDK4/6 genes expression among groups. Flow cytometry revealed that the G0/G1 phase cells significantly increased while S and G2/M phase cells decreased in the miR-370 and the dsP21-555 groups, compared with the dsControl group. Cell proliferation assay showed that, compared with the dsControl group, the proliferative capacities of cells transfected with miR-370 or dsP21-555 decreased significantly (bothP<0.05), but the difference in proliferative capacities between the miR-370 and the dsP21-555 groups was no statistically significant (P>0.05). Colony formation assay showed that the numbers of colonies formed in the miR-370 and the dsP21-555 groups were both smaller than that in the dsControl group.

dsP21-555 may activate the expression of P21 protein by RNA activation, thereby significantly inhibit the growth of bladder cancer cells.

To develop a robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of 5-fluorouracil (5-FU) in blood plasma and evaluate the use of 5-FU for treatment response surveillance as well as toxicity prediction in malignant gastrointestinal tumors.

A LC-MS/MS method was used, with signal linearity, lower limits of quantitation, precision, accuracy and stability being evaluated according to guideline US Food and Drug Administration (FDA)'s guidance for industry bioanalytical method validation.Analysis of 5-FU was performed in 35 gastrointestinal cancer patients admitted to Zhongshan Hospital of Fudan University from April 2013 to December 2013. The relationship between 5-FU with toxicity and treatment effect was compared.

The linear ranges of 5-FU was 49-9 800 ng/ml, the lower limit of quantitation was 49.0 ng/ml. The within-run and between-run coefficients of variation (CV) of 5-FU was <3% and <6%.The recovery rates of low, medium and high level quality controls were 103.36%, 88.12% and 91.26% respectively; with standard added recovery of 109.69%, 91.06% and 88.81% respectively. The control added recoveries were 112.16%, 99.12% and 92.28% respectively. The bias was -11.69%, 2.42% and -8.09% when samples were repeated freezing and thawing twice (-80 ℃). The results had a bias -11.97%, 1.42%, -10.91% and 0.56%, 0.14%, 3.82% when samples were kept at 2-8 ℃ for 2 days and 14 days. In 35 gastrointestinal cancer patients, there was no correlation between initial dose of 5-FU and 44 h AUC (concentration 3.44-53.43 mg/L·h). The risk of chemotherapy-related adverse effect in 5-Fu 44 h AUC> 30 mg/L·h group was significantly higher than 44 h AUC < 30 mg/L·h group (χ ²=12.600, P<0.01). While the chemotherapy response of AUC > 20 mg/L·h group was significantly satisfactory than AUC < 20 mg/L·h group (χ²=5.358, P<0.05).

A robust and reliable LC-MS/MS method for the determination of 5-FU in blood plasma has been developed and it is suitable for clinical application. Detecting 5-FU may guide individualized treatment and predict adverse events.

Aortic dissection is the most dangerous lesion in aortic diseases, with acute onset, rapid progression and serious consequences^[1]。 With the development of surgical and interventional techniques, the efficacy of aortic dissection has improved year by year. However, when Stanford Type B aortic dissection extends to the left subclavian artery or even the distal aortic arch, the treatment plan is more complicated^[2]。 Interventional therapy alone lacks sufficient anchoring area, and traditional surgical procedure is invasive. Hybrid surgery, that is, partial aortic arch artificial blood vessel bypass surgery combined with endovascular aortic isolation, on the one hand, avoids deep hypothermic circulatory arrest, reduces trauma, and simplifies the surgical method; On the other hand, it expands the adaptation range of descending aorta endovascular isolation. In this study, 50 cases of complex Stanford type B aortic dissection were treated by hybrid surgery, and the curative effect was good. The experience is summarized below.

A 58-year-old female was admitted to the Fourth Hospital of Hebei Medical University on June 2, 2015 due to "double lung cancer with multiple bone metastases for 3 years and 10 months and left lower limb pain for 8 months". The patient was admitted to the hospital on 25-Aug-2011 mainly for "left chest pain for 7 d". Cytopathological diagnosis of PET/CT and lung biopsy was that lung cancer of both lungs with multiple bone metastases, which was not suitable for surgical treatment. Multiple cycles of chemotherapy were given, and bone metastasis of thoracic vertebra appeared on October 31, 2012. When the disease progressed, targeted therapy with icotinib hydrochloride was given. On December 18, 2014, the main cause of "double lung cancer with multiple bone metastases for 3 years and pain in the left lower limb for 3 months" was readmitted to hospital. The pain control of oral irecoxib tablets was not satisfactory, so it was changed to morphine sulfate sustained-release tablets 10 mg, orally taken twice a day. The patient was intolerable due to dizziness, nausea and vomiting, so it was changed to diclofenac sodium sustained-release tablets 75 mg, orally taken once a day, but the pain control was still not satisfactory; Fentanyl patch was given 1.4 mg/72 h for external use, and dizziness, nausea, sweating, and palpitation occurred. The symptoms of patients given metoclopramide, ondansetron and other drugs did not improve. Continue to use diclofenac sodium sustained-release tablets to control pain, but the effect is not good. On 7 March 2015, the patient was admitted to the hospital mainly for "left back pain aggravated for 1 d", complaining of pain in the left shoulder and left upper limb. The nature of the pain was described as traction pain and cold pain, which aggravated after activity, affecting sleep, and the pain numerical score (NRS) was>5 points. On 12 Mar 2015, MRI of thoracolumbar spine showed: compression fracture of thoracic 11 vertebral body; Uneven bone signals in thoracic 6, 7 and lumbar 2 vertebrae.

With the deepening of people's understanding, the definition and classification of pulmonary hypertension are constantly being updated. This article is about the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension^[1]The relevant definitions and classification updates are interpreted, and the changes in the guidelines are explained in combination with clinical practice.

Cholangiocarcinoma is a malignant tumor that mainly originates from bile duct epithelial cells. Bile, as the microenvironment of bile duct epithelium, mainly participates in lipid digestion and absorption of fat-soluble vitamins. Bile acids are one of the main components in bile. In recent years, it has been found that bile acids can also be used as signal transduction molecules, participate in oxidative stress in the body, and participate in the development of cholangiocarcinoma through bile acid receptors such as FXR, TGR5 and S1PR2. This paper mainly introduces the relationship between metabolic regulation of bile acids and the development of cholangiocarcinoma at the molecular level.