The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS: From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS: The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS: The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.

Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis: Preliminary experience.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is regarded as a contraindication for liver transplantation (LT) in hepatocellular carcinoma (HCC). However, some of these patients may have a favorable prognosis after LT. In this study, we evaluated the biological behavior of HCC with PVTT using tumor biomarker (alpha-fetoprotein, AFP) and 18F-FDG positron emission tomography (tumor standard uptake value) to identify a subset of patients who may be suitable for LT. METHODS: Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed. Different pre-transplant prognostic factors were identified by univariate and multivariate analyses. PVTT status was identified following Vp classification (Vp1-Vp4). RESULTS: Three-year recurrence-free survival and overall survival rates were 40% and 65.4% in Vp2-Vp3 PVTT patients, 21.4% and 30.6% in Vp4 PVTT patients (P < 0.05). Total tumor diameter >8 cm, pre-transplant AFP level >1000 ng/mL and intrahepatic tumor maximal standard uptake value (SUVmax-tumor >5) were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients. Low risk patients were defined as total tumor diameter ≤8 cm; or if total tumor diameter more than 8 cm, with both pre-transplant AFP level less than 1000 ng/mL and intrahepatic tumor SUVmax less than 5, simultaneously. Twenty-two Vp2-3 PVTT HCC patients (46.8%) were identified as low risk patients, and their 3-year recurrence-free and overall survival rates were 67.6% and 95.2%, respectively. CONCLUSIONS: Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18F-FDG SUVmax might be suitable for LT.

Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation: Preliminary experience.

BACKGROUND: Post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence still occurs in approximately 20% of patients and drastically affects their survival. This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population. METHODS: A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study. Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival. RESULTS: Of the 64 patients with recurrent HCC after LT, those who received radical resection followed by nonsurgical therapy had a median overall survival (OS) of 20.9 months after HCC recurrence, significantly superior to patients who received only nonsurgical therapy (9.4 months) or best supportive care (2.4 months). The one- and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy (93.8%, 52.6%), poor for patients receiving only nonsurgical therapy (30.8%, 10.8%), and dismal for patients receiving best supportive care (0%, 0%; overall P < 0.001). Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months, far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure (12 months, P < 0.001). Compared with tacrolimus-based immunosuppressive therapy, OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence (P = 0.035). Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival. CONCLUSIONS: Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence. A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.

MRC-5 Cancer-associated Fibroblasts Influence Production of Cancer Stem Cell Markers and Inflammation-associated Cell Surface Molecules, in Liver Cancer Cell Lines.

Background: Current opinion suggests that expansion of cancer stem cells (CSCs) and activation of pro-tumoral inflammation cascade correlate with cancer progression. Materials and methods: We explored the possible contributions of MRC-5 cancer-associated fibroblasts to the expression profiles of CSC markers and inflammation-associated cell surface molecules. The liver cancer cell lines Bel-7402, SMMC-7721, MHCC-LM3, and HepG2 cultured in conditioned medium (CM) from MRC-5 served as test groups, whereas the liver cancer cell lines cultured in normal medium served as control groups. Results: Flow cytometry revealed that the proportions of CD90+ cells were significantly higher in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, and moderately higher in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, than in controls. The CD90+/CD45- proportions were elevated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, but reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, as compared to controls. Western blotting indicated that Nanog was downregulated in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls; that POU5F1 (OCT4/3) was downregulated in MHCC-LM3-(MRC-5)-CM, but upregulated in Bel-7402-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls, and that CK19 was upregulated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, compared to controls. Proportions of cells expressing Toll-like receptor-1+ (TLR1) and TLR4 were significantly higher in MHCC-LM3-(MRC-5)-CM cells, and moderately higher in HepG2-(MRC-5)-CM cells, than controls. However, the TLR1+ and TLR4+ proportions were lower in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells than controls. Proportions of CD25+ cells were reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, but elevated in MHCC-LM3-(MRC-5)-CM and Bel-7402-(MRC-5)-CM cells, compared to controls. Proportion of CD61+ cells was higher in liver cancer cells cultured in MRC-5-CM than in controls. Proportion of CD14+ cells was lower in HCC cells cultured in MRC-5-CM than in controls. Conclusion: MRC-5 extensively affected the production of CSC markers and inflammation-associated cell surface molecules. Tumor-targeting molecular therapies should consider these findings.

Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors.

BACKGROUND: Primary hepatic neuroendocrine neoplasms (PHNENs) are extremely rare and few articles have compared the prognosis of PHNENs with other neuroendocrine neoplasms (NENs). This study aimed to investigate the different prognosis between PHNENs and pancreatic NEN (PanNENs) and evaluate the relevant prognosis-related factors. METHODS: From January 2012 to October 2016, a total of 44 NENs patients were enrolled and divided into two groups according to the primary tumor location which were named group PHNENs (liver; n = 12) and group PanNENs (pancreas; n = 32). Demographic, clinical characteristics and survival data were compared between the two groups with Kaplan-Meier method and log-rank tests. Prognostic factors were analyzed using the Cox regression model. RESULTS: The overall survival of group PHNENs and group PanNENs were 25.4 ±â€¯6.7 months and 39.8 ±â€¯3.7 months, respectively (P = 0.037). The cumulative survival of group PanNENs was significantly higher than that of group PHNENs (P = 0.029). Univariate analysis revealed that sex, albumin, total bilirubin, total bile acid, aspartate aminotransferase, alkaline phosphatase, α-fetoprotein and carbohydrate antigen 19-9, histological types, treatments and primary tumor site were the prognostic factors. Further multivariate analysis indicated that albumin (P = 0.008), histological types NEC (P = 0.035) and treatments (P = 0.005) were the independent prognostic factors. Based on the histological types, the cumulative survival of patients with well-differentiated neuroendocrine tumor was significant higher than that of patients with poorly differentiated neuroendocrine carcinoma in group PHNENs (P = 0.022), but not in group PanNENs (P > 0.05). According to the different treatments, patients who received surgery had significantly higher cumulative survival than those with conservative treatment in both groups (P < 0.05). CONCLUSIONS: PHNENs have lower survival compared to PanNENs. Histological types and treatments affect the prognosis. Surgical resection still remains the first line of treatment for resectable lesions and can significantly improve the survival.

[Effects of Aging on Endothelium-dependent Vasodilation of Human Artery].

OBJECTIVE: To determine the effects of aging on endothelium-dependent vasodilation of human artery. METHODS: Vessel tension changes induced by acetylcholine (ACh) and endothelial-derived hyperpolarizing factor (EDHF) on gastroepiploic artery rings were recorded in 15 patients with stomach cancer aged between 51 and 83 years. The mRNA expressions of endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX), cystathionineγ lyase (CSE) and the C-type natriuretic peptide (CNP) in the artery vessels were detected by qRT-PCR. RESULTS: Both endothelium-dependent and EDHF induced vasodilation decreased with age (P<0.05). The mRNA expressions of eNOS, CSE and CNP also decreased with age (P<0.05), except COX. CONCLUSION: Aging could impair the function of endothelium-dependent vasodilation and EDHF-induced vasodialtion of human artery, possibly due to decreased NO, H2S and CNP in artery.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges.

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.

Single-operator wire-guided cannulation technique enables easier cannulation of endoscopic retrograde cholangiopancreatography.

BACKGROUND: The single-operator wire-guided cannulation technique in endoscopic retrograde cholangiopancreatography (ERCP) has been rarely reported. AIMS: This study was undertaken to determine the safety and efficiency of a single-operator wire-guided cannulation technique. METHODS: Four hundred sixty-five consecutive patients referred for ERCP were included in this prospective study and randomly divided into two groups. A new single-operator wire-guided cannulation technique was performed by the same experienced endoscopist, with experienced assistants (group A) and inexperienced ones (group B). The number of attempts at cannulation, cannulation time, success rate, and procedure-related complications were compared between the two groups. RESULTS: Successful cannulation was achieved in 460 out of the 465 patients (98.92 %). The incidences of post-ERCP pancreatitis, bleeding, infection, and perforation were 5.16, 0.64, 1.08, and 0 %, respectively. There were no severe complications or death. The cannulation time, number of attempts at cannulation and complications were not significantly different between the two groups (all P > 0.05). CONCLUSIONS: The single-operator wire-guided cannulation technique was feasible, safe and efficient. It doesn't require an experienced assistant and precise coordination between the assistant and endoscopist during cannulation.

Risk factors and incidence of acute pyogenic cholangitis.

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis. METHODS: We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists. Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC. RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%). Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia, abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariate analysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC. CONCLUSIONS: This study demonstrates that advanced age, hypotension, abnormal WBC, high CRP, and long duration of antibiotic therapy are significantly associated with ASC. We recommend decompression by ERCP should be carried out in patients as early as possible.

[Role of C-type natriuretic peptide receptor and large-conductance calcium-activated potassium channels in brain natriuretic peptide-induced porcine coronary artery dilation].

OBJECTIVE: To investigate the role of C-type natriuretic peptide receptor (NPR-C) and large-conductance calcium-activated potassium channels (BK(Ca)) in brain natriuretic peptide (BNP) induced porcine coronary artery dilation. METHODS: Porcine coronary artery rings were obtained and treated with BNP (10(-6) mol/L), BNP + NPR-C antagonist cANF4-28 (10(-6) mol/L) and BNP + BK(Ca) blocker tetraethylammonium (TEA, 1 mmol/L). The vascular tone experiments were observed on 10 vessel segments. BK(Ca) current density was measured by the whole-cell patch clamp technique. RESULTS: The maximum diastolic rate was similar between BNP group (68.51% ± 11.50%) and cANF4-28 + BNP group (65.67% ± 11.90%, P > 0.05) while significantly reduced in TEA + BNP group (28.87% ± 4.55%, all P < 0.05). When the holding potential was set at +60 mV, the BK(Ca) current density of BNP group was (78.48 ± 5.86) pA/pF, which was significantly higher than control group [(53.84 ± 4.55) pA/pF, P < 0.05], which was equally reduced in the TEA group and TEA + BNP group [(28.80 ± 2.76) pA/pF and (30.60 ± 3.88) pA/pF respectively, all P < 0.05 vs. control group]. CONCLUSION: BNP could relax the porcine coronary arterial smooth muscles by increasing BK(Ca) current, and this effect is not mediated by NPR-C.

Safely Modified Laparoscopic Liver Resection for Segment VI and/or VII Hepatic Lesions Using the Left Lateral Decubitus Position.

Purpose: To explore the feasibility and safety of using the left lateral decubitus position (LLDP) to perform laparoscopic liver resection (LLR) for the treatment of hepatic lesions in segment VI and/or VII. Patients and Methods: Clinical data concerning 50 patients underwent LLR including 25 patients in the LLDP and the other 25 patients in the routine operative position (ROP) at Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College (Hangzhou, China) and Shulan (Quzhou) Hospital between March 2019 and May 2022 were retrospectively analyzed. All of the patients underwent LLR while in the LLDP or the ROP for the treatment of hepatic lesions located in segment VI and/or VII. Results: The preoperative clinical and laboratory parameters were comparable between the two groups (P > 0.05). All patients completed the surgery successfully. There were two patients required conversion to open resection in the ROP comparing with zero in the LLDP. The mean operative time was 256.9 ± 132.7 minutes in LLDP and 255.7 ± 92.1 minutes in ROP, while the median perioperative blood loss was 100 mL (range: 50-300 mL) in LLDP and 200 mL (range: 50-425 mL), respectively. The postoperative pathological examination showed that margin-negative resection was achieved all of the cases. The important postoperative parameters all returned to normal within five days after the LLR. The mean postoperative hospital stay (15.6 vs 19.3 days; p < 0.05) and the extraction of the drainage tube time (7.8 vs 10.4 days; p < 0.05) were shorter for patients in LLDP. Conclusion: The LLDP represents a safe and feasible position for performing LLR in selected patients with lesions in segment VI and/or VII. LLR in the LLDP is helpful in terms of the exposure of the surgical field and the recovery of the patient.

No therapeutic ERCP in anastomotic stricture without intrahepatic biliary dilation after liver transplantation.

BACKGROUND/AIMS: Differentiating surgical jaundice from non-surgical jaundice is of vital importance after liver transplantation (LT) and endoscopic retrograde cholangiopancreatography (ERCP) is not effective for all anastomotic stricture (AS) cases. In the present study, we aim to determine the optimal indication of ERCP treatment for AS after LT. METHODOLOGY: Twenty-eight jaundice patients who underwent successful ERCP treatments for post-transplant AS were classified into two groups: AS with intrahepatic biliary dilation (group 1, n=22) and AS without intrahepatic biliary dilation (group 2, n=6). The outcomes of the two groups were evaluated. RESULTS: The median time intervals from LT to the occurrence of AS were 38 days and 434 days for group 1 and group 2, respectively. The median total bilirubin significantly decreased from 142umol/L to 49umol/L (p<0.05) two weeks after ERCP treatment in group 1. Fourteen patients (63.6%) were cured and for the other 8 the treatment proved effective in group 1. But total bilirubin was not improved after the ERCP treatment in group 2 (p>0.05). CONCLUSIONS: Therapeutic ERCP is not effective in AS without intrahepatic biliary dilation after LT.

Accuracy of brush cytology in biliopancreatic strictures: a single-center cohort study.

OBJECTIVE: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. METHODS: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course. RESULTS: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. CONCLUSIONS: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

[Vasodilatory effects of CNP on aortic arteries of rabbits].

OBJECTIVE: To investigate the mechanism of vasodilatory effects of C-type natriuretic peptide (CNP). METHODS: Tension changes in aortic rings of rabbits were recorded with the presence of CNP or C-type natriuretic peptide receptor (NPR-C) agonist (cANF4-23) after pretreatment with epinephrine (NE) or 60 mmol/L KCl. The vasodilatory effects of four types of potassium channel blocker and NPR-C antagonist (cANF4-28) were also tested. RESULTS: A maximal vasorelaxant effects of (33.5 +/- 5.9) % and (38.4 +/- 10.6)% were recorded in the presence of 1 micromol/L CNP and cANF4-23, respectively, cANF4-28 attenuated the action of CNP [(19.8 +/- 8.3)%]. The vasorelaxant effects of CNP and cANF4-23 decreased significantly after pretreatment with 60 mmol/L KCl (P < 0.01). Glibenclamide and BaCl2 also attenuated the relaxant activities of CNP (P < 0.05). But only BaClZ decreased the vasodilatory action of cANF4-23 (P < 0.05). CONCLUSION: The relaxant activity of CNP is mediated through three paths: NPR-B/KATP, NPR-C/KIR and NPR-C/calcium channels.

[Sodium channel changes in human atrial cells isolated from various ages].

OBJECTIVE: To investigate if the increased incidence of atrial fibrillation with age was associated with changes of Na(+) channel in atrial myocytes. METHODS: Twenty-three patients underwent valve replacement operations were divided into adult [< 60 years, n = 15, 9 males, mean age (42.1 +/- 7.1) years] and aged group [> or = 60 years, n = 8, 5 males, mean age (63.3 +/- 3.1) years]. All patients were in normal sinus rhythm. Whole cell patch clamp techniques were used to record the Na(+) currents (I(Na)) of right auricle myocytes. RESULTS: Both current density and time-dependent recovery of I(Na) were similar in the cells from the 2 groups. Voltage-dependent inactivation of I(Na) of myocytes in the aged atria was shifted to more positive voltages. CONCLUSION: Current density of I(Na) was similar between the 2 age groups, and Na(+) channel might not be an important determinant for the increased incidence of atrial fibrillation in aged patients.

Macrovascular Endothelial Cells Enhance the Motility of Liver Cancer Cells by Up-regulation of MMP-3, Activation of Integrin/FAK Signaling Pathway and Induction of Non-classical Epithelial-mesenchymal Transition.

Background: Liver cancer with portal vein tumor thrombus (PVTT) indicates a serious prognosis. The molecular mechanism of PVTT formation is not totally clarified, the invasion of blood vessels by liver cancer cells is the key step and portal vein endothelial cells plays critical role. Methods: Conditioned medium (CM) of human umbilical vein endothelial cells (HUVEC) were used to culture liver cancer cells and prostate cancer cells for cell motility and viability analysis for the purpose of simulating the role of macrovascular endothelial cells in the development of liver cancer. Results: HUVEC-CM caused long spindle-shaped changes in liver cancer cells; the invasion and migration ability of Bel-7402 and MHCC-LM3 (cultured in HUVEC-CM) increased significantly. Integrins/FAK (focal adhesion kinase) signaling pathway was activated and MMP-3 was up-regulated. However, classical epithelial-mesenchymal transition (EMT) did not involve. HUVEC-CM caused a decrease of cell population in G1- and S-phase of Bel-7402, it also caused an accumulation of cell population in G1 phase and a decrease of cell population in S-phase of MHCC-LM3, MHCC-97L and DU-145. HUVEC-CM promotes apoptosis of Bel-7402 and MHCC-97L and the nude mouse tumorigenic experiment did not find that the HUVEC-CM increase the tumorigenic ability of liver cancer cells. Conclusion: HUVEC may provide an easy-to-adhere roadbed for liver cancer cells invasion of blood vessels by altering extracellular matrix (ECM), activating integrins/FAK pathway and inducing non-classical EMT. The effect of HUVEC-CM on cell viability was cancer cell type dependent. It is a meaningful glance at the mechsanism of PVTT.

Inhibitory effects of tetrandrine on the Na(+) channel of human atrial fibrillation myocardium.

AIM: Tetrandrine (Tet) is a Ca(2+) channel blocker and has antiarrhythmic effects. Less information exists with regard to the mechanisms underlying its antiarrhythmic action other than blocking Ca(2+) channels. In this study, the effects of Tet on the Na(+) current (I(Na)) in the atrial myocardium of patients in atrial fibrillation (AF) and sinus rhythm (SR) were investigated, and the characteristics of the Na(+) current were synchronously compared between the AF and SR patients. METHODS: Na(+) currents were recorded using the whole-cell patch clamp technique in single atrial myocyte of the AF and the normal SR groups. The effects of Tet (40-120 micromol/L) on the Na(+) current in the two groups were then observed. RESULTS: Tet (60-120 micromol/L) decreased I(Na) density in a concentration-dependent manner and made the voltage-dependent activation curve shift to more positive voltages in the SR and AF groups. After exposure to Tet, the voltage-dependent inactivation curve of I(Na) was shifted to more negative voltages in the two groups. Tet delayed the time-dependent recovery of I(Na) in a concentration dependent manner in both AF and SR cells; however, there were no differences in the effects of Tet on I(Na) density and properties in the two groups. The I(Na) density of AF patients did not differ from that of the SR patients. CONCLUSION: Tet can block sodium channels with slow recovery kinetics, which may explain the mechanisms underlying the antiarrhythmic action of Tet. The decreased conduction velocity (CV) in AF patients is not caused by the Na(+) current.