Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Single-Particle Hyperspectral Imaging for Monitoring of Gold Nanoparticle Aggregates in Macrophages.

Gold nanoparticles (Au NPs) have a promising future in the diagnosis and therapy of diseases owing to their unique photoelectric properties. In the body, monodisperse Au NPs may aggregate extracellularly and intracellularly, which influences their in vivo fate and physiological effects. However, due to the lack of a rapid, precise, and high throughput method for characterizing Au NP aggregates, the intricate aggregation process of Au NPs has not yet been fully understood. In order to overcome this obstacle, we develop a single-particle hyperspectral imaging method to identify Au NP aggregates, making use of the outstanding plasmonic properties of monodisperse and aggregated Au NPs. This method enables us to monitor the dynamic formation of Au NP aggregates in biological mediums and cells. Further single-particle hyperspectral imaging analysis reveals that following exposure to 100 nm Au NPs, the formation of Au NP aggregates in macrophages highly depends on exposure dosage and is less affected by exposure duration. In particular, surface coating, including PEGylation and protein corona, can considerably mitigate the intracellular aggregation of Au NPs. Our findings highlight that single-particle hyperspectral imaging is an efficient way for studying how Au NPs aggregate in biological scenarios.

Study on anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy.

BACKGROUND: Patients with malignant tumors are more likely to have psychological problems due to their worries about their life expectancy. To understand the psychological status of elderly patients with malignant liver tumor undergoing hepatectomy better, the study was designed to investigate the current situation of anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy and to analyze its related factors. METHODS: A total of 126 elderly patients with malignant liver tumor undergoing hepatectomy were selected as the research objects. The anxiety and depression of all subjects were evaluated by HADS (Hosptial Anxiety and Depression Scale). The correlation factors affecting the psychological state of elderly patients with malignant liver tumor undergoing hepatectomy were analyzed by linear regression method. RESULTS: The HADS-A score of elderly patients with malignant liver tumor undergoing hepatectomy was 8.79 ± 2.56, among which 37 patients were asymptomatic, 60 patients with suspicious symptoms, and 29 patients with definite symptoms. The HADS-D score was 8.40 ± 2.97, among which 61 patients were asymptomatic, 39 patients with suspicious symptoms, and 26 patients with definite symptoms. Multivariate analysis using linear regression method showed that FRAIL score, residence, and complication were significantly associated with anxiety and depression of elderly patients with malignant liver tumor undergoing hepatectomy. CONCLUSIONS: Anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy were obvious. FRAIL score, regional differences, and the complication were the risk factors for anxiety and depression in elderly patients with malignant liver tumor undergoing hepatectomy. Improving frailty, reducing regional differences, and preventing complications is beneficial to alleviate the adverse mood of elderly patients with malignant liver tumor undergoing hepatectomy.

Quantitative Comparison of Gold Nanoparticle Delivery via the Enhanced Permeation and Retention (EPR) Effect and Mesenchymal Stem Cell (MSC)-Based Targeting.

There are still some gaps in existing knowledge in the field of cancer nanotheranostics, e.g., the efficiency of nanoparticle-loaded cells for targeted delivery. In the current study, gold nanoparticles (Au NPs) were delivered to tumors in both subcutaneous tumor and lung metastasis tumor models by intravenous injection of either free Au NPs or of human bone marrow mesenchymal stem cells (MSCs), which were loaded with endocytosed Au NPs. By making injections with the same dose of administrated Au NPs, it was possible to directly compare tumor targeting of both delivery modes. Hereby, the passive targeting of tumor by the plain Au NPs was facilitated by the enhanced permeation and retention (EPR) effect. Au NP retention by tumors, as well as tumor penetration, were found to be improved up to 2.4-to-9.3-fold when comparing the MSC-mediated delivery of Au NPs to the delivery of the plain Au NPs via EPR effect on day 7 post administration. While the absolute retention of Au NPs in the tumor remained low, our data show that, upon injection of the same amount of Au NPs, in fact MSC-mediated delivery is quantitatively higher than EPR-mediated delivery of NPs by half an order of magnitude.

Engineered Macrophages: A Safe-by-Design Approach for the Tumor Targeting Delivery of Sub-5 nm Gold Nanoparticles.

Ultrasmall nanoparticles (NPs) are a promising platform for the diagnosis and therapy of cancer, but the particles in sizes as small as several nanometers have an ability to translocate across biological barriers, which may bring unpredictable health risks. Therefore, it is essential to develop workable cell-based tools that can deliver ultrasmall NPs to the tumor in a safer manner. Here, this work uses macrophages as a shuttle to deliver sub-5 nm PEGylated gold (Au) NPs to tumors actively or passively, while reducing the accumulation of Au NPs in the brain. This work demonstrates that sub-5 nm Au NPs can be rapidly exocytosed from live macrophages, reaching 45.6% within 24 h, resulting in a labile Au NP-macrophage system that may release free Au NPs into the blood circulation in vivo. To overcome this shortcoming, two straightforward methods are used to engineer macrophages to obtain "half-dead" and "dead" macrophages. Although the efficiency of engineered macrophages for delivering sub-5 nm Au NPs to tumors is 2.2-3.8% lower than that of free Au NPs via the passive enhanced permeability and retention effect, this safe-by-design approach can dramatically reduce the accumulation of Au NPs in the brain by more than one order of magnitude. These promising approaches offer an opportunity to expand the immune cell- or stem cell-mediated delivery of ultrasmall NPs for the diagnosis and therapy of diseases in a safer way in the future.

Perioperative factors related to the prognosis of elderly patients with hepatocellular carcinoma.

BACKGROUND: Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). The treatment of elderly patients with HCC has always been difficult. With the development of geriatrics and geriatric surgery, the number of elderly patients with HCC undergoing hepatectomy has gradually increased. To further improve the long-term prognosis of elderly patients with hepatocellular carcinoma undergoing surgery, it is necessary to study the related perioperative factors. Our aim was to study the impact of preoperative and intraoperative factors on the long-term survival of elderly patients with HCC who underwent hepatectomy. METHODS: A total of 151 elderly patients with HCC who underwent hepatectomy were retrospectively studied. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. RESULTS: The 1-, 3-, 5- and 10-year overall survival rates of elderly patients with HCC who underwent resection were 79.5%, 60.8%, 46.6%, and 25.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis: Child-Pugh grade (B/C versus A: HR[hazard ratio] = 2.318, P = 0.019), alpha-fetoprotein value (> 20 ng/ml versus ≤ 20 ng/ml: HR = 1.972, P = 0.005), resection style (anatomical versus no anatomical: HR = 1.976, P = 0.006), and intraoperative blood loss (> 400 ml versus ≤ 400 ml: HR = 2.008, P = 0.003). CONCLUSIONS: Poor survival of elderly patients with HCC who underwent hepatectomy was correlated with the preoperative and intraoperative factors of Child-Pugh grade, Alpha-fetoprotein value, resection style, and intraoperative blood loss.

Effect of perioperative factors on the prognosis of patients with hepatocellular carcinoma who underwent hepatectomy.

BACKGROUND: Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). Controversy persists regarding preoperative and intraoperative characteristics related to patient survival in various medical institutes. This study aimed to evaluate the impact of preoperative and intraoperative factors on the long-term survival of patients with HCC who underwent hepatectomy. METHODS: Data on 455 patients with HCC who underwent hepatectomy over a 20-year period were retrospectively reviewed. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors. RESULTS: The 1-, 3-, 5-, and 10-year overall survival rates of patients with HCC who underwent resection were 76.3%, 57.9%, 46.7%, and 27.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis-sex (male versus female, hazard ratio [HR] = 2.732, p = 0.026); differentiation (poor versus well, HR = 2.037, p = 0.030); total bilirubin value (µmol/L, HR = 1.056, p = 0.033); and intraoperative blood transfusion (no transfusion versus transfusion, HR = 0.417, p = 0.002). Hepatitis virus B infection (negative versus positive, HR = 0.669, p = 0.232) and resection style (anatomical versus nonanatomical, HR = 0.698, p = 0.181) were not associated with survival. DISCUSSION: Based on this 20-year study, poor survival of patients with HCC who underwent hepatectomy was correlated with preoperative and intraoperative factors including male sex, poor differentiation, increased total bilirubin levels, and intraoperative blood transfusion.

Individualized risk estimation for postoperative pulmonary complications after hepatectomy based on perioperative variables.

BACKGROUND: At present, there is no perfect system to evaluate pulmonary complications of liver surgery using perioperative variables. AIM: To design and verify a risk assessment system for predicting postoperative pulmonary complications (PPCs) after hepatectomy based on perioperative variables. METHODS: A retrospective analysis was performed on 1633 patients who underwent liver surgery. The variables were screened using univariate and multivariate analyses, and graded scores were assigned to the selected variables. Logistic regression was used to develop the liver operation pulmonary complication scoring system (LOPCSS) for the prediction of PPCs. The LOPCSS was verified using the receiver operating characteristic curve. RESULTS: According to the multivariate correlation analysis, the independent factors which influenced PPCs of liver surgery were age [≥ 65 years old/< 65 years old, odds ratio (OR) = 1.926, P = 0.011], medical diseases requiring drug treatment (yes/no, OR = 3.523, P < 0.001), number of liver segments to be removed (≥ 3/≤ 2, OR = 1.683, P = 0.002), operation duration (≥ 180 min/< 180 min, OR = 1.896, P = 0.004), and blood transfusion (yes/no, OR = 1.836, P = 0.003). The area under the curve (AUC) of the LOPCSS was 0.742. The cut-off value of the expected score for complications was 5. The incidence of complications in the group with ≤ 4 points was significantly lower than that in the group with ≥ 6 points (2.95% vs 33.40%, P < 0.001). Furthermore, in the validation dataset, the corresponding AUC of LOPCSS was 0.767. CONCLUSION: As a novel and simplified assessment system, the LOPCSS can effectively predict PPCs of liver surgery through perioperative variables.

Establishment of an Assessment System for the Prediction of Severe Post-operative Complications after Hepatectomy Based on Preoperative Parameters.

OBJECTIVE: At present, there is no appropriate system to evaluate the severe complications of liver surgery through the preoperative factors. This study aimed to design and verify a risk assessment system for the prediction of severe post-operative complications after a hepatectomy based on the preoperative parameters. METHODS: A retrospective analysis was performed on 1732 patients who had undergone liver surgery. The severity of the complications was graded by Accordion Severity Grading of post-operative complications. The variables were screened by multivariate analysis, and graded scores were assigned to the selected variables. A logistic regression equation was used to form the liver operation risk formula (LORF) for the prediction of severe post-operative complications. The LORF was verified by the receiver operating characteristic (ROC) curve. RESULTS: The multivariate correlation analysis revealed the independent influencing factors of the severe post-operative complications of liver surgery were Child-Pugh grade (OR=4.127; P<0.001), medical diseases requiring drug treatment (OR=3.092; P<0.001), the number of liver segments to be removed (OR=2.209; P=0.006), organ invasion (OR=4.538; P=0.024), and pathological type (OR=4.023; P=0.002). The binomial logistic regression model was established to obtain the calculation formula (LORF) of the severe complication risk. The area under the ROC curve (AUC) of the LORF was 0.815. The cut-off value of the expected probability of severe complications was 0.3225 (32.25%). Furthermore, in the validation data set, the corresponding AUC of the LORF was 0.829. CONCLUSION: As a novel and simplified assessment system, the LORF could effectively predict the severe post-operative complications of liver surgery through the preoperative factors, and therefore it could be used to evaluate the risk of severe liver surgical complications before surgery.

Effect of Postoperative ω-3 Fatty Acid Immunonutritional Therapy on NK Cell Gene Methylation in Elderly Patients with Gastric Cancer.

OBJECTIVE: This study aims to investigate the effect of ω-3 fatty acid immunonutritional therapy on natural killer (NK) cell gene methylation and function in elderly patients with gastric cancer. METHODS: A total of 70 cases of elderly patients with gastric cancer were randomized into the ω-3 fatty acid group and placebo group, according to the type of nutritional support administered. The methylation status of the tumor necrosis factor (TNF)-α gene promoter in peripheral NK cells was detected by methylation specific polymerase chain reaction, and the TNF-α level in peripheral NK cells was detected by enzyme-linked immunosorbent assay. RESULTS: After 14 days of immunonutritional therapy with ω-3 fatty acid or placebo, patients in the ω-3 group had significantly higher average NK cell activity (0.27 vs. 0.24, P=0.013) and lower percentages of TNF-α gene promoter methylation (25.7% vs. 60%, P<0.05) than the placebo group. However, there were no significant differences in the concentration of albumin, prealbumin and TNF-α in serum, and the NK cell count between the ω-3 group and placebo group. CONCLUSION: The postoperative application of ω-3 fatty acid may improve the activity of NK cells, which is correlated to the methylation status of the TNF-α gene promoter.

Silver nanoparticles compromise the development of mouse pubertal mammary glands through disrupting internal estrogen signaling.

Despite numerous studies on the environmental health and safety (EHS) of silver nanoparticles (AgNPs), most studies looked into their gross toxicities with rather limited understanding on their labyrinthine implicit effects on the target sites, such as the endocrine system. Burgeoning evidence documents the disrupting effects of AgNPs on endocrine functions; however, little research has been invested to recognize the potential impacts on the mammary gland, a susceptible estrogen-responsive organ. Under this setting, we here aimed to scrutinize AgNP-induced effects on the development of pubertal mammary glands at various concentrations that bear significant EHS relevance. We unearthed that AgNPs could accumulate in mouse mammary glands and result in a decrease in the percentage of ducts and terminal ducts in the adult mice after chronic exposure. Strikingly, smaller sized AgNPs showed greater capability to alter the pubertal mammary development than larger sized particles. Intriguingly, mechanistic investigation revealed that the reduction of epithelial proliferation in response to AgNPs was ascribed to reduced ERα expression, which, at least partially, accounted for diseased epithelial morphology in mammary glands. Meanwhile, the decline in fibrous collagen deposition around the epithelium was found to contribute to the compromised development of mammary glands under the exposure of AgNPs. Moreover, as an extension of the mechanism, AgNPs diminished serum levels of estradiol in exposed animals. Together, these results uncovered a novel toxicity feature of AgNPs: compromised development of mouse pubertal mammary glands through the endocrine-disrupting actions. This study would open a new avenue to unveil the EHS impacts of AgNPs.

Ageing alters the physicochemical properties of silver nanoparticles and consequently compromises their acute toxicity in mammals.

Despite numerous investigations into AgNP-induced toxicity, little has been taken into consideration the potential health impacts of aged AgNPs in comparison to fresh AgNPs. In the current study, we scrutinized the potential effects of aged AgNPs in animals. We first found that AgNPs underwent morphological transformations after natural ageing in aqueous solution upon exposure to air and sunlight for 9 days, as characterized by significant aggregation with increase of particle size approximately by 2 fold. Meanwhile, dissolved Ag ions from aged AgNPs increased by 33% compared to fresh AgNPs. Strikingly, the acute exposure results showed that aged AgNPs induced lower toxicity in mice relative to fresh AgNPs. Aged AgNPs caused milder local inflammation in the peritoneal cavity of mice, as evidenced by 63% reduction of tumor necrosis factor α (TNF-α) than that induced by fresh AgNPs. The deposition mass of aged AgNPs in the liver, spleen, lung and kidney was diminished by 69%, 39%, 83% and 40%, respectively, compared to the distribution profiles in response to fresh AgNPs. Whereby, milder splenic hyperemia was observed, and no significant hepatoxicity was found. Additionally, aged AgNPs provoked milder increase of periphery leukocytes and malondialdehyde (MDA) in mice in comparison to fresh AgNPs. Taken together, this study unraveled that the ageing process elicited remarkable alterations to physicochemical properties and toxic effects as well. This study would provide new insights into the potential health impacts of AgNPs under transformation-determined exposure scenarios.

Protein target identification and toxicological mechanism investigation of silver nanoparticles-induced hepatotoxicity by integrating proteomic and metallomic strategies.

BACKGROUND: Silver nanoparticles (AgNPs), as promising anti-microbials and anti-cancer therapeutics, the toxicological effect and killing efficiency towards cells need in-depth investigation for better applications in daily life and healthcare fields. Thus far, limited studies have yet elucidated the protein targets of AgNPs and silver ions (Ag+) released from intracellular AgNPs dissolution in hepatocytes, as well as potential interaction mechanism. RESULTS: Through integrating proteomic and metallomic methodologies, six intracellular protein targets (i.e. glutathione S-transferase (GST), peroxiredoxin, myosin, elongation factor 1, 60S ribosomal protein and 40S ribosomal protein) were ultimately identified and confirmed as AgNPs- and Ag+ -binding proteins. Toward a deep understanding the direct interaction mechanism between AgNPs and these protein targets, GST was chosen as a representative for toxicological investigation. The results revealed that AgNPs could remarkably deplete the enzyme activity of GST but did not depress the expressions, resulting in elevated intracellular oxidative stress and cell death. Finally, both "Ag+ effect" and "particle-specific effect" were demonstrated to concomitantly account for the overall cytotoxicity of AgNPs, and the former relatively contributed more via activity depletion of GST. CONCLUSIONS: Collectively, our major contribution is the development of an efficient strategy to identify the intracellular AgNPs-targeted protein (e.g. GST) through integrating proteomic and metallomic methodologies, which is helpful to accelerate the interpretation of underlying toxicological mechanism of AgNPs.

Assessment of complications after liver surgery: Two novel grading systems applied to patients undergoing hepatectomy.

Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. The absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome. This study aimed to define and search the simple and reproducible classification of complications following hepatectomy based on two therapy-oriented severity grading system: Clavien-Dindo classification of surgical complications and Accordion severity grading of postoperative complications. Two classifications were tested in a cohort of 2008 patients who underwent elective liver surgery at our institution between January 1986 and December 2005. Univariate and multivariate analyses were performed to link respective complications with perioperative parameters, length of hospital stay and the quality of life. A total of 1716 (85.46%) patients did not develop any complication, while 292 (14.54%) patients had at least one complication. According to Clavien-Dindo classification of surgical complications system, grade I complications occurred in 150 patients (7.47%), grade II in 47 patients (2.34%), grade IIIa in 59 patients (2.94%), grade IIIb in 13 patients (0.65%), grade IVa in 7 patients (0.35%), grade IVb in 1 patient (0.05%), and grade V in 15 patients (0.75%). According to Accordion severity grading of postoperative complications system, mild complications occurred in 160 patients (7.97%), moderate complications in 48 patients (2.39%), severe complications (invasive procedure/no general anesthesia) in 48 patients (2.39%), severe complications (invasive procedure under general anesthesia or single organ system failure) in 20 patients (1.00%), severe complications (organ system failure and invasive procedure under general anesthesia or multisystem organ failure) in 1 patient (0.05%), and mortality was 0.75% (n=15). Complication severity of Clavien-Dindo system and Accordion system were all correlated with the length of hospital stay, the number of hepatic segments resected, the blood transfusion and the Hospital Anxiety and Depression Scale-Anxiety (HADS-A). The Clavien-Dindo classification system and Accordion classification system are the simple ways of reporting all complications following the liver surgery.

Impact of operative and peri-operative factors on the long-term prognosis of primary liver cancer patients undergoing hepatectomy.

This study examined the impact of the operative and peri-operative factors on the long-term prognosis of patients with primary liver cancer undergoing hepatectomy. A total of 222 patients with primary liver cancer who underwent hepatectomy were followed up from January 1986 to December 2010 at Chinese PLA General Hospital. The post-operative complication rate was 14.0% for all cases, 13.7% for hepatocellular carcinoma (HCC), 10.0% for cholangiocarcinoma. The 1-, 3-, 5- and 10-year overall survival rates in patients with primary liver cancer after resection were 76.6%, 57.6%, 41.4%, and 21.0%. The survival rates were significantly higher in the HCC group than in the cholangiocarcinoma group (P=0.000), in the non-anatomical resection group than in the anatomical resection group (P=0.005), in the female group than in the male group (P=0.002), in patients receiving no blood transfusion than in those who were given intra-operative blood transfusion (P=0.000), in patients whose intra-operative blood loss was less than 400 mL than in those who intra-operatively lost more than 400 mL (P=0.000). No significant difference was found in the survival rate between the HBsAg-positive group and the HBsAg-negative group (P=0.532). Our study showed that anatomical resection, blood loss and blood transfusion were predictors of poor survival after hepatectomy for primary liver cancer patients, and concomitant hepatitis B virus infection bore no relation with the post-resection survival.

Expression of scFv-Mel-Gal4 triple fusion protein as a targeted DNA-carrier in Escherichia Coli.

Liver-directed gene therapy has become a promising treatment for many liver diseases. In this study, we constructed a multi-functional targeting molecule, which maintains targeting, endosome-escaping, and DNA-binding abilities for gene delivery. Two single oligonucleotide chains of Melittin (M) were synthesized. The full-length cDNA encoding anti-hepatic asialoglycoprotein receptor scFv C1 (C1) was purified from C1/pIT2. The GAL4 (G) gene was amplified from pSW50-Gal4 by polymerase chain reaction. M, C1 and G were inserted into plasmid pGC4C26H to product the recombinant plasmid pGC-C1MG. The fused gene C1MG was subsequently subcloned into plasmid pET32c to product the recombinant plasmid C1MG/pET32c and expressed in Escherichia coli BL21. The scFv-Mel-Gal4 triple fusion protein (C1MG) was purified with a Ni(2+) chelating HiTrap HP column. The fusion protein C1MG of roughly 64 kD was expressed in inclusion bodies; 4.5 mg/ml C1MG was prepared with Ni(2+) column purification. Western blot and immunohistochemistry showed the antigen-binding ability of C1MG to the cell surface of the liver-derived cell line and liver tissue slices. Hemolysis testing showed that C1MG maintained membrane-disrupting activity. DNA-binding capacity was substantiated by luciferase assay, suggesting that C1MG could deliver the DNA into cells efficiently on the basis of C1MG. Successful expression of C1MG was achieved in E. coli, and C1MG recombinant protein confers targeting, endosome-escaping and DNA-binding capacity, which makes it probable to further study its liver-specific DNA delivery efficacy in vivo.

[Application of persistent methylene blue dyeing method for anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi].

OBJECTIVE: To evaluate the role of anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method. METHODS: From January 2009 to February 2011, 11 hepatocellular carcinoma patients with bile duct tumor thrombi underwent anatomic hepatectomy with removal of the biliary tumor thrombus. There were 10 male and 1 female patients. The average age was 49 years (ranging from 31 to 67 years). The initial symptom of 9 out of the 11 patients was jaundice. After anatomy and ligation of Glissonean pedicle of pre-resection segment, methylene blue was injected into its far-end portal vein in order to dye the segment. RESULTS: Persistent methylene blue dyeing method was successful in all patients. Primary foci were found in all patients. Hepatectomy were performed, including 4 patients of segmentectomy, 3 patients of subsegmentectomy, 2 patients of hemihepatectomy, and 2 patients of hepatic sectionectomy. The mean operation time and blood loss was 137 minutes and 246 ml respectively. Severe complications such as liver function failure and sub-diaphragm abscess was avoided in all patients. No perioperative death. Post-operation radiotherapy was performed on 2 patients . Over a mean follow-up time of 14.6 months, liver cancer recurrence occurred in 2 patients, abdomen seeding metastasis in 1 patient, bile duct tumor thrombi recurrence in 1 case, and 2 patients died. CONCLUSIONS: Anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method can make resection more precise and improve curative effect.

Postoperative transarterial chemoembolization benefits patients with high γ-glutamyl transferase levels after curative hepatectomy for hepatocellular carcinoma: a survival stratification analysis.

Hepatocellular carcinoma (HCC) is the most common liver tumor in Asian countries, and hepatectomy is currently regarded as the optimal curative treatment for HCC; however, the postoperative outcome remains unsatisfactory. Aiming at further clarification of prognostic factors after hepatectomy, we adopted a detailed stratification on survival periods. A total of 428 HCC patients undergoing curative hepatectomy were firstly divided into two groups using 2-year survival as cutoff point. Multivariate analysis showed that tumor-related factors, including vascular invasion (P < 0.001), high Edmondson grade (P < 0.001), large tumor size (P < 0.001) and high serum alpha-fetoprotein level (P = 0.001), were significant determinants for early death within 2 years, while postoperative transarterial chemoembolization (TACE) was demonstrated a protective factor (P = 0.013). Then the 281 patients with survival > 2 years were divided into two subgroups according to survival or death during follow-up to examine the late death related factors. We found that high serum γ-glutamyl transpeptidase (GGT), indicating severity of underlying liver disease, was significantly linked to death in this stage (P = 0.006). In further comparison of survival rates between subgroups stratified by early- and late-death indictors, we found the long-term outcomes of patients with high serum GGT were poor, regardless of the factors related with primary tumor. Furthermore, postoperative TACE decreased late death rate of patients with high GGT levels. In conclusion, despite the overwhelmed effects of primary tumor in the early stage after hepatectomy, postoperative TACE is beneficial for HCC patients with poor liver status.

Resection of hepatic caudate lobe hemangioma: experience with 11 patients.

BACKGROUND: Caudate lobectomy is now considered to be the most appropriate surgical treatment for benign tumors in the caudate lobe. But how to resect the caudate lobe safely is a major challenge to current liver surgery and requires further study. This research aimed to analyze the perioperative factors and explore the surgical technique associated with liver resection in hepatic caudate lobe hemangioma. METHODS: Eleven consecutive patients with symptomatic hepatic hemangiomas undergoing caudate lobectomy from November 1990 to August 2009 at our hospital were investigated retrospectively. All patients were followed up to the present. RESULTS: In this series, 9 were subjected to isolated caudate lobectomy and 2 to additional caudate lobectomy (in addition to left lobe and right lobe resection, respectively). The average maximum diameter of tumors was 9.65+/-4.11 cm. The average operative time was 232.73+/-72.16 minutes. Five of the 11 patients required transfusion of blood or blood products during surgery. Ascites occurred in l patient, pleural effusion in the perioperative period in 1, and multiple organ failure in l on the 6th day after operation as a result of massive intraoperative blood loss, who had received multiple transcatheter hepatic arterial embolization preoperatively. The alternating left-right-left approach produced the best results for caudate lobe surgery in most of our cases. All patients who recovered from the operation are living well and asymptomatic. CONCLUSIONS: For large hemangioma of the caudate lobe, surgery is only recommended for symptomatic cases. Caudate lobectomy of hepatic hemangioma can be performed safely, provided it is carried out with optimized perioperative management and innovative surgical technique.

Interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma.

The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line (Mz-ChA-1) were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.