In recent years,hepatocellular carcinoma (HCC)has become the second leading cause of cancer-related death worldwide.Due to the insidious onset of this disease,only 20%-30%of the patients with HCC have the opportunity for surgical resection or liver transplan-tation.At present,interventional therapy has become the first choice for patients with intermediate-stage HCC and some patients with late-stage HCC,and more and more scholars have realized the importance and necessity of comprehensive interventional therapy for HCC.The comprehensive interventional therapy of transcatheter arterial chemoembolization (TACE)in combination with various methods (TACE com-bined with local treatment,TACE sequential surgery,or TACE combined with systemic treatment)provides many therapeutic approaches and achieves good therapeutic effects.However,the indications,timing,and recurrence and metastasis after treatment for such combination ther-apies await further investigation.

Objective To explore the method and value of percutanously interventional therapeusis for treatment of obstructive jaundice caused by hepatocellular carcinoma accompanied with bile duct thrombosis.Methods Sixteen cases with bile duct thrombosis proved by pathology and imaging examinations were retrospectively analyzed.According to the clinical symptoms, all the patients received percutaneous transhepatic biliary drainage (PTBD) including permanent external drainage, temporary internal drainage and implantation of covered stents.Serum total bilirubin (TBIL) after the interventional therapeusis were measured and compared with that before the treatments by t test to evaluate the efficacy of these treatments.The relief of clinical symptoms was also reviewed to evaluate the efficacy of these treatments.The patients were followed up within 2 years.Results The PTBD was successfully performed in 16 cases.Permanent external drainage, temporary internal drainage and implantation of covered stents were performed in 2 patients, 7 patients and 7 patients respectively.TBIL after the interventional therapy decreased significantly (t=7.366, P<0.01) to (161.2±80.5) μmol/L averagely from (261.9±77.2)μmol/L before the treatments.All the patients died before the end of followed-up.The average survival time was 204 days (30 to 391 d)and the median survival time was 200 days.Bleeding and infection were the main complications, which could be controlled successfully by routine treatments.Conclusion With high achievement ratio and good efficacy, percutanously interventional therapeusis are good choices for the treatments of obstructive jaundice due to bile duct thrombosis.

Objective This study aimed to investigate the incidence and the cause for duodenalbiliary reflux and reflux cholangitis after metallic stent placement in distal common bile duct Methods After percutaneous transhepatic bile duct puncture and biliary outside drainage was performed, 16 cases with malignant distal biliary stricture underwent metallic stent placement in distal common bile duct Before stent placement, the routine laboratory studies including leukocyte, neutrophil percentage and the levels of total bilirubin and direct bilirubin in blood were performed for all patients. Two to five days [ an average of (3.3 ±0. 9) days ] after stent implantation, the above indexes were tested again, and 1 ml of water containing 185 MBq of 99Tcm-DTPA was given orally before extubation, then 99Tcm radioactivity in the bile was detected 2 hours later. For the measurement data obtained from the experiment, t test or Wilcoxon signed rank test was adopted to compare them, and P ＜ 0. 05 was considered to be statistically different Results In 14 cases, radioactivity was successfully detected in the bile 2-5 days after stent implantation. Twelve of them was detected to have radioactivity in the bile 2 hours before extubation with duodenal-biliary reflux. The technetium count in the bile accounted for 1.82% of the total intake dose. There was no radioactivity in the bile in 2 cases. In 14 patients, there were no symptoms of cholangitis such as high fever, chills, increased jaundice, and so on after stent implantation. The mean of white blood cell count was (7.59 t2. 62) × 109/L, and the median of neutrophil percentage was 0. 74. Compared with those before stent implantation, the difference did not reach statistical significance ( t = 0. 423, Z = 1. 036, P ＞ 0. 05 ).After stent implantation, the median of total bilirubin and direct bilirubin were significantly lower, which were 92. 2 and 74. 3 μmol/L. Compared with those before stenting,the difference was statistically significant (Z= -3. 170, -3. 170, P ＜0.05). Conclusions There is a high incidence of duodenal-biliary reflux after stent implantation in distal common bile duct in the early stage. However, there is no simultaneous cholangitis caused by duodenal-biliary reflux.

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （c0） and plasma concentration of voriconazole-N-oxide concentration （cN） were determined， and voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.