Urgent Endoscopy Improves Hemostasis in Patients With Upper Gastrointestinal Bleeding Following Biliary-pancreatic Surgery: A Retrospective Analysis.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a lethal complication of biliary-pancreatic surgery (BPS). The role of endoscopic intervention has not been fully defined in such a critical condition. The aim of this study was to assess the efficacy and safety of endoscopic hemostasis in a retrospective cohort. MATERIALS AND METHODS: Consecutive patients with acute UGIB after BPS who received interventional endoscopy between January 2007 and August 2020 were included in this study. The clinical characteristics were collected and analyzed to screen for predictive factors significantly associated with successful hemostasis. RESULTS: Among 37,772 patients who underwent BPS, 26 patients (0.069%) developed acute UGIB. The sites and causes of hemorrhage were as follows: gastroenteric anastomoe (n=17), gastric stump (n=2), jejunal anastomose (n=1), duodenal bulb ulcer (n=2), pancreatojejunal anastomosis hemorrhage (n=1), cholangiojejunal anastomose (n=1), gastroenteric anastomose and gastric stump hemorrhage (n=1), and Dieulafoy lesion (n=1). Successful endoscopic hemostasis was achieved in 19 (73.1%) of the 26 UGIB patients. In the 7 patients who failed endotherapy, 1 patient received a successful radiologic intervention, 6 patients underwent reoperation and achieved hemostasis in 4, and the other 2 patients died after reoperation. Logistic regression analysis showed that presentation-to-endoscopy time (≤12 h) was the only independent predictive factor associated with successful endoscopic hemostasis. CONCLUSIONS: Endoscopic hemostasis is relatively safe and effective in controlling UIGB after BPS. Prompt intervention (≤12 h) could improve the success rate of endoscopic hemostasis.

Effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma with radical resection.

PURPOSES: This study was designed to evaluate the effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma (GBC) after radical resection (R0). METHODS: A total of 267 GBC patients who underwent R0 resection from January 2004 to December 2014 were enrolled, including 54 patients with preoperative jaundice and 213 patients without jaundice. The clinicopathological parameters between the two groups were compared, and the correlation between preoperative jaundice and the long-term prognosis was furtherly analyzed. RESULTS: Unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT stage was an independent factor for prognosis. Furthermore, the intraoperative blood transfusion and pT stage were significant different between long-term survival (survive for more than 3 years) and those who died within 3 years (P < 0.05). CONCLUSION: Preoperative jaundice was not the independent factor resulting in the poor long-term prognosis of gallbladder carcinoma after R0 resection. The pT stage was the only long-term prognostic factor in all GBC patients regardless of preoperative jaundice.

STAT3 overexpression promotes metastasis in intrahepatic cholangiocarcinoma and correlates negatively with surgical outcome.

Signal transducer and activator of transcription 3 (STAT3) promotes tumor progression in many types of cancer. In this study, we analyzed the prognostic value of this marker in human intrahepatic cholangiocarcinoma (ICC). Using real-time PCR, western blot and immunohistochemistry assays, we found that STAT3 is overexpressed in ICC patients. STAT3 expression correlated with several clinicopathological features, including tumor size, pathological satellite, vascular invasion, undifferentiated-type histology, lymph node metastasis and TNM stage in two independent cohorts of ICC patients. Patients with high STAT3 levels had a poor prognosis in terms of overall survival (OS) and disease-free survival (DFS). Multivariate survival analysis indicated that STAT3 is an independent prognostic factor for OS and DFS. Furthermore, we observed that STAT3 overexpression promotes the invasion, metastasis and proliferation of ICC cells in vitro and in vivo, and also promotes STAT3 phosphorylation. These findings suggest that STAT3 expression correlated negatively with surgical outcome and inhibition of STAT3 expression may constitute a novel target for the treatment of ICC patients.

Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy.

BACKGROUND: Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). METHODS: DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. RESULTS: The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. CONCLUSION: The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.

The prognostic importance of jaundice in surgical resection with curative intent for gallbladder cancer.

BACKGROUND: Preoperative jaundice is frequent in gallbladder cancer (GBC) and indicates advanced disease. Resection is rarely recommended to treat advanced GBC. An aggressive surgical approach for advanced GBC remains lacking because of the association of this disease with serious postoperative complications and poor prognosis. This study aims to re-assess the prognostic value of jaundice for the morbidity, mortality, and survival of GBC patients who underwent surgical resection with curative intent. METHODS: GBC patients who underwent surgical resection with curative intent at a single institution between January 2003 and December 2012 were identified from a prospectively maintained database. RESULTS: A total of 192 patients underwent surgical resection with curative intent, of whom 47 had preoperative jaundice and 145 had none. Compared with the non-jaundiced patients, the jaundiced patients had significantly longer operative time (p < 0.001) and more intra-operative bleeding (p = 0.001), frequent combined resections of adjacent organs (23.4% vs. 2.8%, p = 0.001), and postoperative complications (12.4% vs. 34%, p = 0.001). Multivariate analysis showed that preoperative jaundice was the only independent predictor of postoperative complications. The jaundiced patients had lower survival rates than the non-jaundiced patients (p < 0.001). However, lymph node metastasis and gallbladder neck tumors were the only significant risk factors of poor prognosis. Non-curative resection was the only independent predictor of poor prognosis among the jaundiced patients. The survival rates of the jaundiced patients with preoperative biliary drainage (PBD) were similar to those of the jaundiced patients without PBD (p = 0.968). No significant differences in the rate of postoperative intra-abdominal abscesses were found between the jaundiced patients with and without PBD (n = 4, 21.1% vs. n = 5, 17.9%, p = 0.787). CONCLUSIONS: Preoperative jaundice indicates poor prognosis and high postoperative morbidity but is not a surgical contraindication. Gallbladder neck tumors significantly increase the surgical difficulty and reduce the opportunities for radical resection. Gallbladder neck tumors can independently predict poor outcome. PBD correlates with neither a low rate of postoperative intra-abdominal abscesses nor a high survival rate.

Applied anatomy of small branches of the portal vein in transverse groove of hepatic hilum.

PURPOSE: The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum. METHODS: According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as "Short hepatic portal veins (SHPVs)". SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured. RESULTS: There were 181 SHPVs in 30 liver specimens, including 46% (83/181) from the left portal vein, 31% (56/181) from the bifurcation, and 23% (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22% (40/181) supplied for segment IV, 9% (17/181) for segment V, 4% (7/181) for segment VI, 23% (41/181) for segment VII, and 42% (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3-12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm. CONCLUSIONS: SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

The outcome of ipsilateral hemihepatectomy in mucin-producing bile duct tumors.

BACKGROUND: Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases. METHODS: Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed. RESULTS: The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence. CONCLUSION: Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.

Expression of aryl hydrocarbon receptor in relation to p53 status and clinicopathological parameters in breast cancer.

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis. However, the role of AhR in tumorigenesis of breast cancer remains unclear. In the current study, we investigated the expression levels of AhR in breast lesions and assessing the correlation between AhR expression and clinicopathological variables using breast cancer tissue microarray. Meanwhile, 10 paired of fresh breast cancer and corresponding non-cancer samples were detected for AhR and p53 expression by Western blot, respectively. Results showed that AhR expression levels in breast cancer tissues were significantly higher than that in the non-cancer tissues. AhR expression was associated with the pathological type and P53 status, but not patients age, tumor grade and TNM, as well as ER, PR, C-erbB2, Ki-67, AR, EGFR status. Moreover, Western blot data suggested a negative correlation between p53 protein and AhR protein expression levels. The results suggest that high levels of AhR were expressed in the majority of breast cancer tissues and closely associated with P53 status and histological types of breast cancer. AHR and its abnormal expression may play an important role in multiple stages of breast cancer progression.

A new anastomosis method for choledochojejunostomy by the way behind antrue pyloricum.

BACKGROUND: Reflux cholangitis has been the most common complication after Roux-en-Y choledochojejunostomy. In this study we intended to evaluate the perioperative and long-term efficacy of a new anastomosis method for choledochojejunostomy. METHODS: Clinical data of 143 eligible patients who underwent choledochojejunostomy in the Eastern Hepatobiliary Surgery Hospital affiliated to the Second Military Medical University, China between January 2007 and December 2010 were retrospectively analyzed. Among the patients, 38 consecutive cases underwent this new anastomosis method for choledochojejunostomy (improved group, IG) and 105 underwent standard Roux-en-Y choledochojejunostomy (control group, CG). Changes in the incidence of cholangitis, the time of beginning to eat liquid meals, post-operative delayed gastric emptying and liver function between the two groups were compared. RESULTS: There was no statistical difference in the levels of alanine transaminase, alkaline phosphomonoesterase and gamma-glutamy transferase between the two groups. The time of beginning to eat liquid meals was significantly shorter in IG than CG (P < 0.05). The incidence of delayed gastric emptying was lower in IG than CG, with statistical tendency between the two groups (P = 0.052). Among nine patients with different degrees of acute cholangitis in the two groups, one patient (2.6%) in IG and eight (7.6%) in CG suffered from acute cholangitis within six months of follow-up after discharge, but with no statistical difference between the two groups (P > 0.05). Of the nine patients with acute cholangitis, none in IG and four in CG were hospitalized for further treatment (P > 0.05). CONCLUSIONS: Patients in IG had satisfactory perioperative and long-term prognosis with shorter time of beginning to eat liquid meals and lower incidence of delayed gastric emptying. This new procedure of choledochojejunostomy by the way behind antrue pyloricum was easy and safe to perform with no mortality and low complication rates.

Differential regulation of bone marrow-derived endothelial progenitor cells and endothelial outgrowth cells by the Notch signaling pathway.

Endothelial progenitor cells (EPCs) are heterogeneous populations of cells that participate in vasculogenesis and promote tissue regeneration. However the different roles of EPC populations in vasculogenesis and tissue regeneration, as well as their regulation and mechanisms remain elusive. In the present study, we cultured bone marrow (BM)-derived early EPCs (EEPCs) and endothelial outgrowth cells (EOCs), and investigated their roles in liver regeneration and their regulation by the Notch signaling pathway. We found that Notch signaling exhibited different effects on the proliferation and migration of EEPCs and EOCs. Our results also showed that while EEPCs failed to form vessel-like structures in a three dimensional sprouting model in vitro, EOCs could sprout and form endothelial cords, and this was regulated by the Notch signaling. We further showed that, by using a conditional knockout model of RBP-J (the critical transcription factor mediating Notch signaling), Notch signaling differentially regulates EEPCs and EOCs. In a partial hepatectomy (PHx) model, EEPCs Notch-dependently benefitted liver regeneration with respect to liver function and hepatocyte proliferation and apoptosis. In contrast, EOCs appeared not directly involved in the recovery of liver function and the increase of hepatocytes. These data suggested that the RBP-J-mediated Notch signaling differentially regulated the two types of EPCs, which showed different roles in liver regeneration.

Soluble extracellular domains of human SIRPα and CD47 expressed in Escherichia coli enhances the phagocytosis of leukemia cells by macrophages in vitro.

Signal regulatory protein (SIRP) α, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. Here, we consider an alternative way to interrupt the interaction between CD47 and SIRPα. We expressed the extracellular domains of the human SIRPα (hSIRP(ext)) and the human CD47 (hCD47(ext)) in Escherichia coli as Trx fusion proteins, and purified them by using affinity chromatography. We show that the purified fusion protein Trx-SIRP(ext) could interact in vitro with Trx-hCD47(ext). Moreover, Trx-SIRP(ext) could effectively bind to Jurkat T-ALL cells, which expressed CD47 at a high level. CD47(ext), on the other hand, bound to human macrophages. In vitro phagocytosis assay showed that these fusion proteins could enhance the phagocytosis of Jurkat cells by macrophage, with Trx-hSIRP(ext) showed a higher efficiency than Trx-CD47(ext). These results indicated that the soluble Trx-hSIRP(ext) and Trx-CD47(ext) polypeptides could be alternative molecules to interrupt CD47-SIRPα interaction between leukemia cells and macrophages, and might be potentially useful for the targeted therapy of leukemia.

Diagnosis and surgical treatment of mucin-producing bile duct tumors.

BACKGROUND/AIMS: To summarize the experience of diagnosis and surgical treatment of mucin-producing bile duct tumors (MPBTs). METHODOLOGY: A retrospective analysis was undertaken to determine the radiography characteristics and results of surgical treatment of MPBTs over the past 9 years. Only eight patients underwent such treatment. The detailed data of diagnosis, treatment and prognosis were carefully studied. RESULTS: Intermittent jaundice was the most frequently clinical manifestation of MPBTs, with unique characteristics on magnetic resonance cholangiopancreatography (MPCP) when compared with gallbladder carcino-ma, hilar cholangiocarcinoma and distal bile duct can-cer. All the 8 patients with MPBTs received appropriate surgical procedure and were cured. CONCLUSIONS: Appropriate diagnosis and curative hepatectomy for MPBTs made it possible to achieve long-term survival.

Correlation between the survival rate of the patients with synchronous hepatic metastases from gastric carcinoma after surgical resection and patient's index.

BACKGROUND: Many studies have reported the benefit of hepatic resection for solitary and metachronous metastases from gastric cancer. However, indications and surgical results for synchronous hepatic metastases from gastric carcinoma have not been clearly defined. This study was performed to assess the benefits and limits of simultaneous combined resection of both primary gastric cancer and synchronous hepatic metastases, as well as to identify prognostic factors affecting the survival. METHODS: Between January 2005 and June 2008, 13 patients with synchronous hepatic metastases underwent simultaneous combined resection. The clinicopathologic features and the surgical results of the 13 patients were retrospectively analyzed. Patient, tumor (primary and metastatic carcinoma), and operative parameters were analyzed for their influence on survival. RESULTS: No patient died and two patients (15.4%) developed complications during peri-operative course. The actuarial 6-month, 1-year, and 2-year survival rates after hepatic resection were 76.9%, 38.5%, and 30.8%, respectively, and two patients survived for more than 2 years after surgery without any signs of recurrences until latest follow-up. In univariate analysis, hepatic tumor distribution (P=0.01) and number of hepatic metastases (P=0.003) were significant prognostic factors that influenced survival. Factors associated with the primary lesion were not significant prognostic factors. CONCLUSIONS: Satisfactory survival may be achieved by simultaneous combined resection of both primary gastric cancer and synchronous hepatic metastases in strictly selected patients. The number of hepatic metastases and hepatic tumor distribution are significant prognostic determinants of survival.

MicroRNA-203 leads to G1 phase cell cycle arrest in laryngeal carcinoma cells by directly targeting survivin.

Previous studies have shown that miR-203 acts as a tumor-suppressive microRNA in various cancers, but its roles in laryngeal carcinoma are still contradicted. Here, we found that miR-203 inhibited the growth of laryngeal cancer cells and survivin was a direct target of miR-203. Moreover, silencing of survivin recapitulated the effect of miR-203 on cell cycle progression, whereas overexpression of survivin reversed this effect. Additionally, qRT-PCR showed the reciprocal relationship between miR-203 and survivin in laryngeal cancer tissues. These findings indicate that miR-203 inhibits the proliferation of laryngeal carcinoma cells by directly targeting survivin, suggesting its application in anti-cancer therapeutics.

Analysis of the relationships between clinicopathologic factors and survival in gallbladder cancer following surgical resection with curative intent.

BACKGROUND: This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent. METHODS: Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome. RESULTS: The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues. CONCLUSIONS: Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians.

Diagnosis and surgical treatment of primary hepatic lymphoma.

AIM: To assess the benefits and limits of surgery for primary hepatic lymphoma (PHL), and probability of survival after postoperative chemotherapy. METHODS: A retrospective analysis was undertaken to determine the results of surgical treatment of PHL over the past 8 years. Only nine patients underwent such treatment. The detailed data of diagnosis, treatment, and prognosis were carefully studied. RESULTS: All patients were mistaken as having α-fetoprotein-negative hepatic cancer before pathological diagnosis. The mean delay time between initial symptoms and final diagnosis was 26.8 d (range: 14-47 d). Hepatitis B virus infection was noted in 33.3% of these patients. Most of the lesions were found to be restricted to a solitary hepatic mass. The surgical procedure performed was left hepatectomy in five cases, including left lateral segmentectomy in three. Right hepatectomy was performed in three cases and combined procedures in one. One patient died on the eighth day after surgery, secondary to hepatic insufficiency. The cumulative 6-mo, 1-year, and 2-year survival rates after hepatic surgery were, respectively, 85.7%, 71.4%, and 47.6%. One patient survived for > 5 years after surgery without any signs of recurrence until latest follow-up, who received routine postoperative chemotherapy every month for 2 years and then regular follow-up. By univariate analysis, postoperative chemotherapy was a significant prognostic factor that influenced survival (P = 0.006). CONCLUSION: PHL is a rare entity that is often misdiagnosed, and has a potential association with chronic hepatitis B infection. The prognosis is variable, with good response to early surgery combined with postoperative chemotherapy in strictly selected patients.

A novel DNA vaccine constructed by heat shock protein 70 and melanoma antigen-encoding gene 3 against tumorigenesis.

Melanoma antigen-encoding gene 3 (MAGE-3) is an ideal candidate for a tumor vaccine although its potency need to be increased. Heat shock proteins (HSPs) represents a potential approach for increasing the potency of DNA vaccines. In the present study, a fusion DNA vaccine composed of Mycobacterium tuberculosis HSP70 and MAGE-3 was constructed and used to immunize C57BL/6 mice against B16 or B16-MAGE-3 tumor cells. The results show that the HSP70-MAGE-3 fusion DNA vaccine enhanced the frequency of MAGE-3-specific cytotoxic T-cells as compared to the MAGE-3 DNA vaccine or the HSP70/MAGE-3 cocktail DNA vaccine (P < 0.05). In conclusion, the results indicate that the HSP70-MAGE-3 fusion DNA vaccine can strongly activate MAGE-3 specific cellular immunological reactions and thus significantly inhibit the growth of B16-MAGE-3 tumors, improving the survival of tumor-bearing mice, and the HSP70-MAGE-3 fusion DNA vaccine has a significant therapeutic effect on the tumors that express MAGE-3 antigens.

[Kv1.3 potassium channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome].

OBJECTIVE: To study the Kv1.3 channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome (ACS). METHODS: CD4(+)T cell in 27 ACS patients and CD4(+)CD28(null)/CD4(+)CD28(+)T cells in 12 out of these 27 ACS patients were isolated from peripheral blood with magnetic cell sorting. The whole-cell Kv1.3 currents for three T cells were recorded with patch-clamp technique before and 72 hours after activation by purified anti-human CD3 Interferon gamma, tumor necrosis factor alpha (TNF-alpha), granzyme B mRNA expression were determined by reverse transcription-PCR before and 72 hours after activation by purified anti-human CD3 in the presence or absence of recombinant Margatoxin (rMgTX, 0.1, 1, 10 nmol/L), a specific Kv1.3 channel blocker. RESULTS: Peak Kv1.3 channel currents of CD4(+), CD4(+)CD28(null), CD4(+)CD28(+)T cells were significantly increased and the mean Kv1.3 channel numbers per cell of these cells were increased by about 90%, 60%, 80% (402 +/- 88 vs. 752 +/- 275, 553 +/- 328 vs. 874 +/- 400, 392 +/- 133 vs. 716 +/- 251, all P < 0.05) after activation compared to baseline values. Baseline CD4(+)CD28(null)T cell numbers were about 40% more than those of CD4(+)CD28(+)T cell (P < 0.05) and were similar after activation (P = 0.102). The mRNA expression of interferon gamma, TNF-alpha and granzyme B were dose-dependently down-regulated by rMgTX. CONCLUSIONS: Kv1.3 channels of peripheral CD4(+)T cell and CD28(null)/CD28(+)T cells from ACS patients significantly increased after activation and Kv1.3-specific channel blocker rMgTX could effectively abolish this effect suggesting a potential role of Kv1.3 channel blocker on plaque stabilization in ACS patients.