The anti-atherosclerotic effect of Paeonol against the lipid accumulation in macrophage-derived foam cells by inhibiting ferroptosis via the SIRT1/NRF2/GPX4 signaling pathway.

Atherosclerosis (AS) is the underlying cause of many severe vascular diseases and is primarily characterized by abnormal lipid metabolism. Paeonol (Pae), a bioactive compound derived from Paeonia Suffruticosa Andr., is recognized for its significant role in reducing lipid accumulation. Our research objective is to explore the link between lipid buildup in foam cells originating from macrophages and the process of ferroptosis, and explore the effect and mechanism of Pae on inhibiting AS by regulating ferroptosis. In our animal model, ApoE-deficient mice, which were provided with a high-fat regimen to provoke atherosclerosis, were administered Pae. The treatment was benchmarked against simvastatin and ferrostatin-1. The results showed that Pae significantly reduced aortic ferroptosis and lipid accumulation in the mice. In vitro experiments further demonstrated that Pae could decrease lipid accumulation in foam cells induced by oxidized low-density lipoprotein (LDL) and challenged with the ferroptosis inducer erastin. Crucially, the protective effect of Pae against lipid accumulation was dependent on the SIRT1/NRF2/GPX4 pathway, as SIRT1 knockdown abolished this effect. Our findings suggest that Pae may offer a novel therapeutic approach for AS by inhibiting lipid accumulation through the suppression of ferroptosis, mediated by the SIRT1/NRF2/GPX4 pathway. Such knowledge has the potential to inform the creation of novel therapeutic strategies aimed at regulating ferroptosis within the context of atherosclerosis.

Inhibition of growth of hepatocellular carcinoma by co-delivery of anti-PD-1 antibody and sorafenib using biomimetic nano-platelets.

BACKGROUND: Traditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments. MATERIALS AND METHODS: Targeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved. RESULTS: These biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth. CONCLUSIONS: The aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).

Age and incidence of occult pancreaticobiliary reflux in patients with benign gallbladder diseases.

BACKGROUND: Occult pancreaticobiliary reflux (OPBR) has a significant correlation with diseases of the gallbladder and biliary system. This study examined the incidence of OPBR by age in patients with benign gallbladder diseases. METHODS: We assessed 475 patients with benign gallbladder diseases who underwent surgery at Shanghai East Hospital from December 2020 to December 2021. Bile samples collected during surgery were tested for amylase. Patients with bile amylase >110 U/L (n = 64) were classified as the OPBR group; the rest (n = 411) as controls. RESULTS: Of the participants, 375 had gallbladder stone (GS), 170 had gallbladder polyp (GP), and 49 had gallbladder adenomyomatosis (GA). The OPBR group was generally older, with OPBR incidence increasing with age, peaking post-45. Rates by age were: 4.9% (<35), 5.2% (35-44), 20.7% (45-54), 22.5% (55-64) and 17.6% (≥65), mainly in GS patients. ROC analysis for predicting OPBR by age yielded an area under the curve of 0.656, optimal cut-off at 45 years. Logistic regression indicated age > 45, GP, male gender, and BMI ≥ 24 kg*m-2 as independent OPBR predictors in GS patients. Based on these variables, a predictive nomogram was constructed, and its effectiveness was validated using the ROC curve, calibration curve and decision curve analysis (DCA). Further stratification revealed that among GS patients ≤ 45, concurrent GA was an OPBR risk; for > 45, it was GP and male gender. CONCLUSIONS: The incidence of OPBR in GS patients is notably influenced by age, with those over 45, especially males without GP, being at heightened risk.

Identification of changes in bile composition in pancreaticobiliary reflux based on liquid chromatography/mass spectrometry metabolomics.

INTRODUCTION: Pancreaticobiliary reflux (PBR) can induce gallstone formation; however, its pathogenic mechanism remains unclear. In this study, we explored the mechanism of PBR by the non-targeted metabolomic analysis of bile in patients with PBR. OBJECTIVE: The aim of this study was to investigate the pathogenic mechanism in PBR by the non-targeted metabolomic analysis of bile collected during surgery. METHODS: Sixty patients who underwent gallstone surgery at our center from December 2020 to May 2021 were enrolled in the study. According to the level of bile amylase, 30 patients with increased bile amylase ( > 110 U/L) were classified into the PBR group, and the remaining 30 patients were classified into the control group (≤ 110 U/L). The metabolomic analysis of bile was performed. RESULTS: The orthogonal projections to latent structure-discriminant analysis of liquid chromatography mass spectrometry showed significant differences in bile components between the PBR and control groups, and 40 metabolites were screened by variable importance for the projection value (VIP > 1). The levels of phosphatidylcholine (PC) and PC (20:3(8Z,11Z,14Z)/14:0) decreased significantly, whereas the levels of lysoPC (16:1(9z)/0:0), lysoPC (15:0), lysoPC (16:0), palmitic acid, arachidonic acid, leucine, methionine, L-tyrosine, and phenylalanine increased. CONCLUSIONS: Significant differences in bile metabolites were observed between the PBR and control groups. Changes in amino acids and lipid metabolites may be related to stone formation and mucosal inflammation.

Design, Synthesis of Hydrogen Peroxide Response AIE Fluorescence Probes Based on Imidazo [1,2-a] Pyridine.

Hydrogen peroxide (H2O2), a significant member of reactive oxygen species, plays a crucial role in oxidative stress and cell signaling. Abnormal levels of H2O2 in the body can induce damage or even impair body function, leading to the development of certain diseases. Therefore, real-time monitoring of H2O2 in living cells is very important. In this work, the aggregation-induced emission fluorescence probe 2-(2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl) oxy) phenyl) imidazo [1,2-a] pyridine (B2) was designed and synthesized, which enables the long-term tracing of H2O2 in living cells. The addition of H2O2 to probe B2 results in a dramatic fluorescence enhancement around 500 nm. Notably, B2 can visualize both exogenous and endogenous H2O2 in living cells. The synthesis method for B2 is simple, has a high yield, and utilizes readily available materials. It exhibits advantages such as low toxicity, photostability, and good biocompatibility. Consequently, the developed fluorescent probe in this study has great potential as a reliable tool for determining H2O2 in living cells.

Hybrid Multimaterial 3D Printing Using Photocuring-While-Dispensing.

Three-dimensional (3D) printing methods, such as vat photopolymerization (VPP) and direct-ink-writing (DIW) processes, are known for their high-resolution and multimaterial capabilities, respectively. Here a novel hybrid 3D printing technique that combines the strengths of VPP and DIW processes to achieve multimaterial and high-resolution printing of functional structures and devices, is presented. The method involves dispensing liquid-like materials via syringes into a photocurable matrix material and subsequently using a Galvano mirror-controlled laser beam to selectively photocure the dispensed material trace or the matrix material surrounding the trace. The laser beam scanning and syringe dispensing are synchronized with a set delay to control liquid diffusion and in situ fixture. The versatility of the method is demonstrated by fabricating intricate 3D ant and wheel prototypes using various materials available for VPP and DIW technologies. The proposed photocuring-while-dispensing strategy offers advantages over conventional multimaterial 3D printing methods, such as integrating materials regardless of photocurability and viscosity, and fabricating heterogeneous structures with complex geometries and high resolution. With its principle demonstrated, this multimaterial 3D printing process will open up a wide range of potential applications with diverse functionalities and materials.

Lesions in White Matter in Wilson's Disease and Correlation with Clinical Characteristics.

BACKGROUND: Neuroimaging studies in Wilson's disease (WD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these alterations are localized to specific regions of fiber tracts, and what diagnostic value they might have. The purpose of this study is to explore the spatial profile of WM abnormalities along defined fiber tracts in WD and its clinical relevance. METHODS: Ninety-nine patients with WD (62 men and 37 women) and 91 age- and sex-matched controls (59 men and 32 women) were recruited to take part in experiments of diffusion-weighted imaging with 64 gradient vectors. The data were calculated by FMRIB Software Library (FSL) software and Automated Fiber Quantification (AFQ) software. After registration, patient groups and normal groups were compared by Mann-Whitney U test analysis. RESULTS: Compared with the controls, the patients with WD showed widespread fractional anisotropy reduction and mean diffusivity, radial diffusivity elevation of identified fiber tracts. Significant correlations between diffusion tensor imaging (DTI) parameters and the neurological Unified Wilson's Disease Rating Scale (UWDRS-N), serum ceruloplasmin, and 24-h urinary copper excretion were found. CONCLUSIONS: The present study has provided evidence that the metrics of DTI could be utilized as a potential biomarker of neuropathological symptoms in WD. Damage to the microstructure of callosum forceps and corticospinal tract may be involved in the pathophysiological process of neurological symptoms in WD patients, such as gait and balance disturbances, involuntary movements, dysphagia, and autonomic dysfunction.

Large-scale networks changes in Wilson's disease associated with neuropsychiatric impairments: a resting-state functional magnetic resonance imaging study.

BACKGROUND: In Wilson's disease (WD) patients, network connections across the brain are disrupted, affecting multidomain function. However, the details of this neuropathophysiological mechanism remain unclear due to the rarity of WD. In this study, we aimed to investigate alterations in brain network connectivity at the whole-brain level (both intra- and inter-network) in WD patients through independent component analysis (ICA) and the relationship between alterations in these brain network functional connections (FCs) and clinical neuropsychiatric features to understand the underlying pathophysiological and central compensatory mechanisms. METHODS: Eighty-five patients with WD and age- and sex-matched 85 healthy control (HC) were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the resting-state networks (RSNs) using the ICA method, analyzed the changes of FC in these networks and the correlation between alterations in FCs and clinical neuropsychiatric features. RESULTS: Compared with HC, WD showed widespread lower connectivity within RSNs, involving default mode network (DMN), frontoparietal network (FPN), somatomotor network (SMN), dorsal attention network (DAN), especially in patients with abnormal UWDRS scores. Furthermore, the decreased FCs in the left medial prefrontal cortex (L_ MPFC), left anterior cingulate gyrus (L_ACC), precuneus (PCUN)within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-neurological characteristic examination (UWDRS-N), and the decreased FCs in the L_MPFC, PCUN within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-psychiatric symptoms examination (UWDRS-P). We additionally discovered that the patients with WD exhibited significantly stronger FC between the FPN and DMN, between the DAN and DMN, and between the FPN and DAN compared to HC. CONCLUSIONS: We have provided evidence that WD is a disease with widespread dysfunctional connectivity in resting networks in brain, leading to neurological features and psychiatric symptoms (e.g. higher-order cognitive control and motor control impairments). The alter intra- and inter-network in the brain may be the neural underpinnings for the neuropathological symptoms and the process of injury compensation in WD patients.

Chemical Profiling and Quantification of Potential Bioactive Components in Gandouling Pill by Ultra-High Performance Liquid Chromatography Coupled with Diode Array Detector/Quadruple-Qrbitrap Mass Spectrometry.

Gandouling (GDL) Pill is a novel Traditional Chinese medicinal drug to treat Wilson's disease in clinics. It is composed of six separate herbal medicines, including Rhei Radix ET Rhizoma, Coptidis Rhizoma, Salviae Miltiorrhizae Radix ET Rhizoma, Spatholobi Caulis, Curcumae Rhizoma, and Curcumae Longae Rhizoma. In this study, a strategy was proposed to investigate the chemical constituents and to quantify the potential bioactive components in GDL Pill. Firstly, the mass fragmentation behaviors of representative compounds were investigated, and, in total, 69 compounds were characterized in GDL Pill using full scan/dd-MS2 scan mode by ultra-high-performance liquid chromatography (UPLC)/Q-Orbitrap mass spectrometry (MS). These compounds included 18 alkaloids, 18 ketones, 16 phenolic compounds, 11 organic acids, and 6 tanshinones. Seventeen of the compounds were unambiguously identified by comparison with reference standards. Secondly, the absorption components of GDL Pill in rat plasma were investigated by using target-Selected Ion Monitoring (t-SIM) scan mode built in Q-Orbitrap MS. A total of 18 components were detected, which were considered as potential bioactive components of GDL Pill. Thirdly, 10 major absorption components were simultaneously determined in six batches of samples by UPLC/diode array detector (DAD). The method was fully validated with respect to linearity, precision, repeatability, stability, and recovery. Alkaloids from Coptidis Rhizoma, such as coptisine (8), berberine (18), palmatine (19), were the most abundant bioactive compounds for GDL Pill that possess the potential be used as quality markers. The proposed strategy is practical and efficient for revealing the material basis of GDL Pill, and also provides a simple and accurate method for quality control.

Free fatty acids and triglyceride change in the gallbladder bile of gallstone patients with pancreaticobiliary reflux.

BACKGROUND: Pancreaticobiliary reflux (PBR) causes chronic inflammation of the gallbladder mucosa and changes in the bile components, which are known to promote gallstone formation. This study aimed to investigate the bile biochemistry changes in gallstone patients with PBR and provide new clues for research on the involvement of PBR in gallstone formation. METHODS: Patients undergoing surgery for gallstones between December 2020 and May 2021 were eligible for inclusion. The bile biochemistry (including amylase, lipase, triglyceride, cholesterol, free fatty acids [FFAs], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ-glutamyl transferase [γ-GT]) of the included gallstone patients was analysed to determine correlations with PBR. RESULTS: In this study, 144 gallstone patients who underwent surgery were enrolled. Overall, 15.97 % of the patients had an increased bile amylase level, which was associated with older age and significantly higher bile levels of ALP, lipase, triglyceride, and FFAs. Positive correlations were observed between amylase and lipase, triglyceride, FFAs levels in the gallbladder bile. However, the bile levels of triglyceride, FFAs, and lipase were positively correlated with each other only in the PBR group and showed no significant correlation in the control (N) group. In addition, elevated bile FFAs levels were found to be an independent risk factor for gallbladder wall thickening. CONCLUSIONS: In conclusion, PBR-induced increase in FFAs and triglyceride in the gallbladder bile is a cause of gallstone formation, and an increase in bile ALP suggests the presence of cholestasis in PBR.

Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR-17-5p/ PTEN axis in gastric cancer.

OBJECTIVES: This study was conducted to identify the significantly altered long noncoding RNAs (lncRNAs), messenger RNA (mRNA) and pathways in gastric cancer (GC). METHODS: We used microarray analysis to identify differentially expressed lncRNAs and mRNAs, whereas the obviously changed pathways were found by gene set enrichment analysis. The coexpression network of lncRNA and mRNA was constructed by Cytoscape, and their target relationships with miRNAs were predicted by miRcode and TargetScan. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins in tissues and cell lines. Dual-luciferase reporter assay was applied to achieve the determination of the specific target relationships. Cell viability, migration, and apoptosis were detected by MTT assay, wound healing assay and flow cytometry, respectively. Through the xenograft assay, the gastric tumor was implanted into nude mice to investigate the influence of HOTAIRM1 in vivo. RESULTS: HOTAIRM1 and phosphatase and tensin homolog (PTEN) were both downregulated in GC, whereas miR-17-5p was upregulated. Moreover, the PI3K/AKT pathway was found activated in GC. HOTAIRM1 targeted miR-17-5p, whereas PTEN was the downstream target gene of miR-17-5p. HOTAIRM1 suppressed proliferation and migration of GC cell line and induced their apoptosis, whereas miR-17-5p played the opposite role on GC cell line. HOTAIRM1 also postponed tumor growth in vivo and inhibited the PI3K/AKT pathway in GC. CONCLUSIONS: LncRNA HORAIRM1 suppressed the PI3K/AKT pathway in GC and inhibited the progression of GC by serving as a competing endogenous RNA of miR-17-5p, mediating the expression of PTEN.

N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis.

Osteoarthritis (OA), characterized by cartilage damage, synovitis inflammation and chronic pain, is a common degenerative joint disease that may lead to physical disability. In the present study, we first explored the association between N-Acylethanolamine acid amidase (NAAA) and OA progression, and then examined the capability of the NAAA inhibitor F215 to attenuate osteoarthritis. Increased NAAA expressions and decreased PEA levels in synovial membrane and lumbar spinal cord were observed in MIA induced osteoarthritic rats. F215 (i.a., and i.p.) significantly protected against cartilage damage and synovial inflammation by directly increasing PEA levels in joints, or normalization of PEA levels and resolution of inflammation in spinal cord. Moreover, F215 also markedly alleviated osteoarthritic pain in rats, and the therapeutic effects of F215 were blocked by the PPAR-α antagonist MK886. The results revealed that NAAA may has been implicated in OA progression, and treatment with NAAA inhibitor F215 alleviated OA development by preventing cartilage damage, reducing inflammation, and alleviating pain. Our study suggested that NAAA inhibitor might be a novel therapeutic agent for OA treatment.

A novel method: using an adenosine triphosphate (ATP) luminescence-based assay to rapidly assess the biological stability of drinking water.

The rapid and credible evaluations of the microbial stability of a drinking water distribution system (DWDS) are of great significance for ensuring the safety of drinking water and predicting microbial pollution. Conventional biostability assessment methods mainly focus on bacterial regrowth or evaluation of the level of nutrients that support bacterial regrowth. However, such methods are time-consuming and have many limitations. An adenosine triphosphate (ATP) assay can rapidly measure all active microorganisms and is known to be a useful method to assess the microbial activity of drinking water. The measurement of ATP has been used for more than a decade in the field of drinking water research. This article reviews the application of an ATP luminescence-based method to assess the biostability of drinking water and discusses the feasibility of ATP measurement as a parameter for quickly evaluating this criterion. ATP measurement will help researchers and water managers better monitor the biological stability of drinking water from the source to the consumer's tap. This review covers the: (1) principle and application of the ATP measurement in drinking water quality assessment; (2) comparison of the merits and demerits of several methods for evaluating the biostability of drinking water; (3) discussions on using ATP measurement in evaluating biostability; and (4) improvements in the use of ATP measurement in evaluating biostability. At the end of this review, recommendations were given for better application of the ATP measurement as a parameter for monitoring the microbial quality of drinking water.

Jaundice caused by protrusion of a hepatic cyst into common bile duct that was resolved by choledochoscopic needle-knife electrotomy: a case report.

BACKGROUD: Hepatic cysts are the most frequent, innocuous, space-occupying lesions of the liver. The majority of solitary liver cysts are nonsymptomatic. When liver cysts reach a large size, there are some complications, including infection, rupture, spontaneous hemorrhage, obstructive jaundice, and neoplastic degeneration. Percutaneous aspiration, fenestration, hepatic resection, and liver transplantation have been proposed for symptomatic patients. CASE PRESENTATION: In this case report, we describe a 41-year-old woman who presented with persistent liver dysfunction, indolent xanthochromia, and skin itching for 3 months. After a series of tests, she has a 5.0 × 5.3 cm hepatic cyst with many separations in the left medial liver lobe. The obstructive jaundice was caused by a large pedunculated lump protruding into the common bile duct from the left hepatic duct. She was treated with laparotomy and this lump was completely removed from the root by choledochoscopic needle-knife electrotomy with a good clinical response. Postoperative pathology of the lump suggested a hepatic cyst wall without heterocysts or tumor cells. CONCLUSION: Hepatic cyst wall protruding into the common bile duct can form capsular lump and result in indolent jaundice. Choledochoscopic high-frequency needle-knife electrotomy could be considered as a simple, safe and effective complementary approach for benign mass on the bile duct wall.

The modified pancreatic stent system for prevention of post-ERCP pancreatitis: a case-control study.

BACKGROUND: Prophylactic pancreatic stents after endoscopic retrograde cholangiopancreatography (ERCP) can help prevent post-ERCP pancreatitis. However most of the pancreatic stents need to be removed by another ERCP. The aim of this observational study was to investigate the feasibility and effectiveness of the modified pancreatic stent system for prevention of post-ERCP pancreatitis. METHODS: From November 2013 to November 2015, a total of 230 patients who had prophylactic pancreatic stent placed for prevention of post-ERCP pancreatitis at a single institution were identified and stratified. In this case-control design, 150 patients received an ordinary pancreatic stent, and 80 patients received the modified pancreatic stent. The main outcome measures were the difficulty level and complications of pancreatic stent placement and extraction between the two groups. RESULTS: In ordinary group, the average time of pancreatic stent and nasal biliary drainage placement was 3.5 ± 0.6 min. There were 13 cases of stent proximal migration (8.7%), 20 cases of stent spontaneous abscission (13.3%), 5 cases of acute pancreatitis (3.3%) (2 cases for stent abscission) and 7 cases of hyperamylasemia (4.7%) after ERCP. One hundred thirty patients received extra duodenoscope (86.7%) to remove the stent, and 4 cases had acute pancreatitis and 5 patients had hyperamylasemia after removing the proximal migratory stents. In modified group, the average time of pancreatic stent system placement was 4.9 ± 0.7 min, but there was only one case of stent abscission (1.3%), 2 cases of acute pancreatitis (2.5%) and 3 cases of hyperamylasemia (3.8%). The new pancreatic stents were removed directly under x-ray without complication. CONCLUSIONS: The modified pancreatic stent system has the same effect of preventing post-ERCP pancreatitis, lower rate of stents proximal migration and spontaneous abscission, and the advantage of easier removed compared with ordinary pancreatic stent.

An approximate model on three-dimensional groundwater infiltration in sewer systems.

Groundwater infiltration through cracked sewer pipes has caused significant economic losses. This paper presents a three-dimensional analytical expression for calculating the steady-state groundwater infiltration rate into sewer systems. As an extension of the previously developed two-dimensional model by the author, this new model can be used to simulate the infiltration through an orifice defect. The derived analytical expression has been validated with experimental results. The new model incorporates all the related resistances during the infiltration process, including the soil head loss and the orifice loss. The soil head loss is assessed with Ergun equation, which involves an inertial loss term in addition to the viscous loss. This has significantly extended the application range of the new expression. A new OS number (the ratio of orifice loss to soil loss) expression is also presented. The order analysis of the OS number expression has demonstrated that in most real cases, the head loss through the soil layer dominates the whole infiltration process.

A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase.

BACKGROUND: Both dasatinib and nilotinib are approved frontline therapy for chronic myeloid leukemia in chronic phase (CML-CP) based on randomized trials compared with imatinib. However, no head-to-head comparison of dasatinib and nilotinib has been conducted in patients with newly diagnosed CML-CP. METHODS: The authors conducted a propensity score (PS) matched comparison of patients with CML-CP who received frontline therapy with either dasatinib (N = 102) or nilotinib (N = 104) under the respective phase 2 trials conducted in parallel. RESULTS: PS matching resulted in 87 patients from each trial being matched for pretreatment characteristics. The 3-month BCR-ABL1/ABL1 ratio <10% rate was 93% with dasatinib and 94% with nilotinib (P = .25); the rates of major molecular response at 12 months were 77% and 85%, respectively (P = .13); and the rates of molecular response with 4.5-log reduction in the ratio at 36 months were 66% and 64%, respectively (P = .96). All other clinically relevant responses were similar between the 2 treatment cohorts. The 3-year probability of event-free survival was 89% among the patients who received dasatinib and 87% among those who received nilotinib (P = .99), and the corresponding 3-year overall survival probabilities were 99% and 93%, respectively (P = .95). No statistical difference was observed between the dasatinib and nilotinib groups in any of the other survival endpoints. The treatment discontinuation rate also was similar between the 2 cohorts (dasatinib group, 18%; nilotinib group, 19%; P = .82). CONCLUSIONS: In a PS-matched cohort of patients with newly diagnosed CML-CP, dasatinib and nilotinib offer similar response and survival outcomes. Both drugs can be considered reasonable standard-of-care options as first-line therapy for patients with CML-CP. Cancer 2016;122:3336-3343. © 2016 American Cancer Society.

Hyperfibrinogenemia predicts poor prognosis in patients with advanced biliary tract cancer.

Hyperfibrinogenemia reportedly predicts poor prognosis in several cancers but has not been reviewed for biliary tract cancer (BTC). The aim of the present study was to evaluate associations between baseline plasma fibrinogen concentrations, clinicopathological characteristics, and survival parameters in patients with BTC. Data for 127 patients with BTC diagnosed at the Zhongshan Affiliated Hospital of Dalian University (Liaoning, China) from January 2011 to December 2014 were retrospectively evaluated. Associations between baseline fibrinogen concentrations, selected clinicopathological characteristics, and the prognostic value were examined using SPSS software. Data for 37 patients (29.1 % of study cohort) who had undergone curative intent surgery and 90 (70.9 %) with advanced biliary tract cancer (ABTC) were analyzed. The mean plasma fibrinogen concentration 4.0 ± 0.9 g/L for the entire cohort. The percentages with hyperfibrinogenemia (>4 g/L) were 45.7, 37.8, and 48.9 % overall and in the surgical and ABTC groups, respectively. Hyperfibrinogenemia was associated with performance status (PS) and neutrophil/lymphocyte ratio in the entire cohort but not with other relevant clinicopathological factors. Log-rank test indicated that baseline hyperfibrinogenemia was associated with decreased progression-free survival (PFS) and overall survival (OS) for patients with unresectable ABTC (P > 0.05). Multivariate analysis showed that poor PS and baseline hyperfibrinogenemia were independently associated with worse survival (HR: 1.39, 95 % CI: 1.02-1.90, P = 0.04; HR: 1.75.95 %, 95 % CI: 1.01-3.01, P = 0.04, respectively). Baseline hyperfibrinogenemia is an independent predictor of poor prognosis in patients with ABTC. Baseline plasma fibrinogen concentrations may be a readily available and inexpensive prognostic biomarker in patients with ABTC; this needs further validation in large prospective clinical trials.

Choledochoscopic high-frequency needle-knife electrotomy for treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy.

BACKGROUND: Anastomotic stricture is a complex and substantial complication following Roux-en-Y hepaticojejunostomy. Initially, endoscopic and percutaneous approaches are often attempted, but the gold standard remains surgical biliary reconstruction, especially for refractory stricture. However, this solution leaves much room for improvement, due to the challenging nature of the biliary reconstruction procedure, in which anastomotic stricture may still occur. AIMS: To investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy as an intervention in the treatment of anastomotic strictures following Roux-en-Y hepaticojejunostomy. METHODS: From February 2010 to October 2014, clinical data was collected and retrospectively compared for patients who underwent balloon dilation or/and choledochoscopic high-frequency needle-knife electrotomy for the treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy. RESULTS: A total of 38 patients underwent successful choledochoscopic treatment and all the anastomotic strictures were removed successfully, 19 of which were treated with electrotomy, 7 with balloon dilation, and 12 with both electrotomy and balloon dilation. Among these groups,the average operating times were 6.9 ± 2.4 min,10.1 ± 6.8 min, and 20.2 ± 13.5 min, respectively. The average stent supporting times were 6.3 ± 0.7 months, 6.5 ± 0.6 months, and 6.1 ± 0.4 respectively. The mean follow-up after stent removal was 42.1 ± 27.4 months, and in 26.3 % (5/19), 28.5 % (2/7) and 16.7 % (2/12) of cases, recurrent anastomotic stricture occurred. Of these 9 total patients with recurrent anastomotic, two patients were successfully rescued by full-covered self-expanding removable metal stents and 7 patients by electrotomy combined with balloon dilation. CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy is both feasible and safe in the treatment of anastomotic stricture after Roux-en-Y hepaticojejunostomy, with a similar long-term outcome to balloon dilation in treating anastomotic stricture after Roux-en-Y hepaticojejunostomy. A combination of choledochoscopic electrotomy concurrent with balloon dilation should be recommended based on the low rate of recurrence.

Choledochoscopic high-frequency needle-knife electrotomy as an effective treatment for intrahepatic biliary strictures.

BACKGROUND AND AIM: Hepatolithiasis is associated with the presence of intrahepatic biliary strictures, and balloon dilatation is the main approach. However, this method is difficult to implement if the bile duct distal to the stricture is blocked by stones. Therefore, alternative methods need to be explored to effectively treat hepatolithiasis. The aim of this study is to investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy for the treatment of intrahepatic biliary strictures. METHODS: Clinical data of 58 patients suffering from intrahepatic bile duct strictures from January 2011 to January 2013 were retrospectively analyzed. Choledochoscopic electrotomy was used to resolve the strictures. RESULTS: One hundred thirty-four sites of intrahepatic bile duct strictures were discovered. The average operating time of electrotomy is 5.6 min (range, 1 ∼ 15 min). Structured bile duct tissue bleeding occurred in eight sites (8/134, 6.0%) but were resolved by endoscopic high-frequency electric cautery. After the operations, 14 cases of cholangitis (14/58, 24.1%), three cases of delayed hemobilia, one case of liver abscess (1/58, 1.7%), and seven cases of stenting exodus (7/58, 12.1%) were observed despite conservative treatment and stenting reset. The average supporting time was 7.0 months (6 ∼ 9 months). No abnormal bile duct structure or presence of stone was found according to choledochoscopy. The follow-up period ranged from 12 to 48 months. Hepatolithiasis recurred in five (5/58, 8.6%) patients, and the cumulative recurrent probability of intrahepatic bile duct stricture was 5.2% (7/134). CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy could be considered as a simple, safe, and effective complementary approach for treating intrahepatic biliary strictures.