Objective:To investigate the feasibility and safety of endoscopic ultrasound (EUS)-guided intrahepatic portal vein puncture through jugular vein implantation in transjugular intrahepatic portosystemic shunt (TIPS).Methods:As research subjects, 5 beagle dogs were anesthetized, and EUS was placed through the jugular vein to observe the intrahepatic portal vein. Under real-time guidance, the portal vein was punctured and a stent was placed to complete the TIPS.Results:Among the 5 beagles, EUS was unable to be placed in 1 due to the small diameter of the external jugular vein, and it was implanted successfully in 4 others through the external jugular vein who underwent real-time guidance of portal vein puncture. Subsequent stent placement and balloon dilation were completed. All animals survived after the experiment.Conclusion:EUS-guided intrahepatic portal vein puncture through jugular vein implantation is safe and feasible in TIPS.

Transjugular intrahepatic portosystemic shunt （TIPS） has been recommended as a treatment method for cirrhotic portal hypertension in domestic and foreign guidelines， but there is still uncertainty in its therapeutic efficacy. More and more studies have shown that TIPS combined with collateral vessel embolization （TIPS+E） has certain advantages in the treatment of gastroesophageal variceal bleeding in liver cirrhosis. This article reviews the major studies on TIPS+E in China and globally， summarizes related recommendations in guidelines and the current status of clinical application， and proposes the issues that need to be solved， such as indication， hemodynamic criteria， and selection of materials for embolization， and large－sample multicenter randomized controlled trials are needed for further clarification.

Transplant rejection involves natural immune cells and acquired immune cells. For decades, acquired immune cells have been dominating the study of transplant immunity. Researchers have found the surprising new features of innate immune cells, including immune memory, which may be of great significance to further improve graft survival. The short-term survival rate of grafts is very good, but the long-term graft outcomes are less so and most transplants are eventually lost to chronic rejection in the clinic. In animal models and clinical studies, innate immune cells, especially macrophages and natural killer cells, often predominate the chronic rejection process which lead grafts lost. Recent studies suggest that innate immune cells are capable of acquiring adaptive features in that they either directly recognize the allografts or become "trained" in the allogeneic milieu to further acquire features of memory and donor specificity. In selected transplant models, targeting the adaptive features of innate immune cells has been shown to promote long-term graft survival. Clearly, these findings highlight new therapeutic opportunities in further improvement of transplant outcomes as well as in treatment of cancers and autoimmune diseases in the clinic. The authors summarize the literature reports, introduce the recent acquired response characteristics of natural immune cells, and stimulate researchers to carry out more exploration in this field by fully discussing the heterogeneity and plasticity of natural immune cell types and the outstanding problems in related field.

Objective:To observe whether α1 adrenergic receptor (α1AR) blocker can reduce and antagonize portal hypertension caused by α1AR activation in rats, and to provide a new approach for the clinical treatment of portal hypertension.Methods:Phenylephrine was chosen as α1AR agonist, and alfuzosin was used as α1AR blocker. The route of administration was portal vein injection, and the pressure was measured by trans-portal vein puncture. According to random number table, 32 male Sprague-Dawley rats were divided into 4 groups: control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group. The portal venous pressure (PVP) was measured in all rats before administration. The rats in the control group were injected with 0.9% sodium chloride solution (1 L/g), and the rats in portal hypertension model group were injected with phenylephrine(1.5 μg/g), and the PVP of the above two groups was measured again at 5 and 10 min after injection. The rats in alfuzosin treatment group were injected with phenylephrine(1.5 μg/g), PVP was measured again at 5 min after administration, and then the rats were given alfuzosin(0.9 μg/g), PVP was measured again at 5 min after administration. The rats in alfuzosin prevention group were injected with alfuzosin(0.9 μg/g), PVP was measured at 1 min after administration, and then the rats were given phenylephrine(1.5 μg/g), PVP was measured again at 1, 5 and 10 min after phenylephrine injection respectively. One way analysis of variance and Dunnett- t test were used for statistical analysis. Results:The portal vein puncture was successfully performed in 4, 6, 8 and 5 rats in the control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group, respectively. The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was (18.045±7.636) and (15.515±5.440) mmHg (1 mmHg = 0.133 kPa), respectively, which were both higher than that before administration ((8.452±2.830) mmHg), and the differences were statistically significant ( t=2.89 and 2.82, both P<0.05). At 5 min after alfuzosin injection, the PVP of rats in the alfuzosin treatment group was (10.088±3.743) mmHg, which was lower than that of rats at 5 min after phenylephrine injection ((16.146±4.324) mmHg) and that of portal hypertension model group at 10 min after phenylephrine injection, and the differences were statistically significant ( t=3.00 and 2.22, both P<0.05). There were no significant differences in PVP in the alfuzosin prevention group before administration, at 1 min after injection of alfuzosin, and at 1, 5 and 10 min after injection of phenylephrine (all P > 0.05). Conclusions:α1AR is an important factor involved in the regulation of PVP, and its blockers can reduce and antagonize the portal hypertension caused by α1AR activation, which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt.Methods:The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results:A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet ( P=0.037) and total bilirubin ( P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage ( P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency ( P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation ( P=0.017), all-cause rebleeding ( P<0.001), postoperative significant hepatic encephalopathy ( P<0.012), and postoperative new or worsening ascites ( P<0.001) was significantly associated with stent occlusion ( P<0.05), while platelets ( P=0.134), total bilirubin ( P=0.229), international normalized ratio ( P=0.436), and portal vein pressure ( P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion:In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.

ObjectiveTo investigate the technical success rate and outcome of transjugular intrahepatic portosystemic shunt (TIPS) in preventing esophageal variceal rebleeding in patients with portal vein thrombosis (PVT) after splenectomy. MethodsA retrospective analysis was performed for the clinical data of 46 patients with PVT after splenectomy who were admitted to Shandong Provincial Hospital from December 2009 to January 2017 and underwent TIPS to prevent esophageal variceal rebleeding. According to the success or failure of TIPS, the patients were divided into TIPS success group with 38 patients and TIPS failure group with 8 patients. The two groups were compared in terms of postoperative variceal rebleeding, stent dysfunction, hepatic encephalopathy (HE), and survival. The paired t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier curve was used to analyze variceal rebleeding-free rate, stent patency rate, HE-free rate, and survival rate, and the log-rank test was used for comparison of cumulative rebleeding-free rate and cumulative survival rate. ResultsThe technical success rate of TIPS was 82.6%. There were significant differences in 6-, 12-, and 24-month cumulative rebleeding-free rates between the TIPS success group and the TIPS failure group (94.3%/89.8%/89.8% vs 85.7%/85.7%/28.6%, χ2=4.563, P=0.033). In the TIPS success group, the 6-, 12-, and 24-month cumulative stent patency rates were 79.3%, 74.3%, and 69.0%, respectively, and the 6-, 12-, and 24-month cumulative HE-free rates after TIPS were 72.1%, 55.5%, and 55.5%, respectively. There were significant differences in 6-, 12-, and 24-month cumulative survival rates between the TIPS success group and the TIPS failure group (94.0%/94.0%/86.2% vs 714%/71.4%/71.4%, χ2=4.988, P=0.026). ConclusionTIPS is a safe and feasible method for preventing esophageal variceal rebleeding in patients with PVT after splenectomy, and TIPS combined with a percutaneous transhepatic approach may promote technical success.

Objective To evaluate the efficacy and safety of X-ray guided endoscopic gastrojejunostomy using stent in treatment of malignant gastric outlet obstruction ( GOO ) . Methods Six hospitalized patients with malignant GOO underwent X-ray guided endoscopic gastrojejunostomy using stent in the department of gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University between March 2017 and June 2017. The technical success rate, clinical success rate, procedure time, adverse events and follow-up were recorded and analyzed in this retrospective study. Results The stent was successfully placed in the 6 patients with 100％ ( 6/6) technical success rate. The mean procedure time was 91. 7±51. 8 min. After the procedure, all patients were fed liquid or semi-liquid diet, and the GOO score system was increased from 0-1 before operation to 2-3 after operation. The clinical success rate was 100％(6/6). Peritonitis was observed in 2 patients during operation, and resolved by abdominal drainage. Gastrointestinal bleeding occurred in 1 patient after operation, which was resolved with conservative treatment. During a mean follow-up period of 78. 6 days (range 32-100 days), there was no recurrence of obstruction symptoms except that 1 patient died because of tumor progress 60 days after procedure. Conclusion The X-ray guided endoscopic gastrojejunostomy using stent is feasible and safe to treat malignant GOO with a reliable short-term efficacy.

Objective: To summarize and analyze the clinical data of hepatic venous pressure gradient (HVPG) and to explore the application value of HVPG in the diagnosis, evaluation and clinical treatment of portal hypertension in cirrhosis. Methods: The patient data of HVPG measurement performed in Shandong Provincial Hospital from April 2010 to November 2017 were collected. Results: A total of 633 patients with 833 times of HVPG measurements were included. There was significant difference in HVPG between patients with different etiologies, different Child-pugh grades and different degrees of decompensated cirrhosis. Conclusion The HVPG test is suitable for the diagnosis and evaluation of portal hypertension. The HVPG of patients with different severity of liver cirrhosis can guide the choice of the treatment plan, and the HVPG measurement should also be strictly standardized and quality control.

Objective To investigate the effects of desmopressin acetate and pituitrin on the proliferation,contraction,and secretion of hepatic stellate cells (HSCs).Methods The human HSC cell line LX-2 was selected as the research model.And three groups were designed:blank control group,desmopressin acetate group (three subgroups:1 × 10-10 mol/L,1 × 10-9 mol/L,and 1 × 10-8 mol/L desmopressin acetate),and pituitrin group (three subgroups:0.1 U/L,1.0 U/L,and 10.0 U/L pituitrin).Water-soluble tetrazolium salt (WST)-1 assay was used to evaluate cell proliferation;collagen gel contraction assay was used to assess cell contraction;enzyme-linked immunosorbent assay (ELISA) was used to identify cell secretion.The data was subjected to one-way analysis of variance.Results (1) The results of WST-1 assay showed that the values of A450 in three desmopressin acetate subgroups (1× 10-10 mol/L,1 × l0-9 mol/L,and 1 × 10-8 mol/L) were 0.459±0.017,0.467±0.024,and 0.436±0.015,respectively.And the values of A450 in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 0.495±0.011,0.507±0.015,and 0.501±0.009,respectively.Compared with the control group,the desmopressin acetate at high concentration significantly inhibited the cell proliferation (P ＜ 0.05),but the pituitrin at three different concentrations significantly promoted the cell proliferation (P ＜ 0.05).(2) The collagen gel area ratios in three desmopressin acetate subgroups (1 × 1010 mol/L,1 × 10-9 mol/L,and 1 × 10-8 mol/L) were 77.07±4.42,75.85±3.70,and 72.74±3.92,respectively.And the collagen gel area ratios in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 57.83±3.96,50.28±6.69,and 43.56±7.68,respectively.Compared with the control group,the pituitrin at three different concentrations significantly reduced the collagen gel area (P ＜ 0.01).(3) The matrix metalloproteinase (MMP)-2 concentrations in three desmopressin acetate subgroups (1× 10-10 mol/L,1 × 10-9 mol/L,and 1×108 mol/L) were 13.321±0.098,12.230±0.153,and 12.061±0.126,respectively.And the MMP-2 concentrations in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 12.899±-0.150,13.662±0.152,and 13.698±0.119,respectively.Compared with the control group,the desmopressin acetate at low concentration significantly increased the secretion of MMP-2 (P ＜ 0.01);the desmopressin acetate at high concentration significantly decreased the MMP-2 concentration (P ＜ 0.05);the pituitrin at three different concentrations significantly increased the MMP-2 concentration (P ＜ 0.01).The transforming growth factor-beta 1 (TGF-β1) concentrations in three desmopressin acetate subgroups (1×10-10 mol/L,1×10-9 mol/L,and l×10-8 mol/L) were 5.233±0.102,17.749±0.188,and 36.060±0.227,respectively.And the TGF-β1 concentrations in three pituitrin subgroups (0.1 U/L,1.0 U/L,and 10.0 U/L) were 15.615±0.099,38.460±0.209,and 49.053±0.115,respectively.Compared with the control group,desmopressin acetate and pituitrin significantly promoted the secretion of TGF-[β1 in a concentration-dependent manner (P ＜ 0.01) and pituitrin had a stronger effect than desmopressin acetate (P ＜ 0.01).Desmopressin acetate and pituitrin had no effect on the secretion of the collagenase type Ⅰ and Ⅲ (P ＞ 0.05).Conclusion Desmopressin acetate and pituitrin can induce the changes in the function and morphology of HSCs and may increase vascular resistance in the hepatic sinus.However,desmopressin acetate has less influence on HSCs than pituitrin.