Integrated Platform for Large-Scale Quantitative Profiling of Phosphotyrosine Signaling Complexes Based on Cofractionation/Mass Spectrometry and Complex-Centric Algorithm.

The scarcity and dynamic nature of phosphotyrosine (pTyr)-modified proteins pose a challenge for researching protein complexes with pTyr modification, which are assembled through multiple protein-protein interactions. We developed an integrated complex-centric platform for large-scale quantitative profiling of pTyr signaling complexes based on cofractionation/mass spectrometry (CoFrac-MS) and a complex-centric algorithm. We initially constructed a trifunctional probe based on pTyr superbinder (SH2-S) for specifically binding and isolation of intact pTyr protein complexes. Then, the CoFrac-MS strategy was employed for the identification of pTyr protein complexes by integrating ion exchange chromatography in conjunction with data independent acquisition mass spectrometry. Furthermore, we developed a novel complex-centric algorithm for quantifying protein complexes based on the protein complex elution curve. Utilizing this algorithm, we effectively quantified 216 putative protein complexes. We further screened 21 regulated pTyr protein complexes related to the epidermal growth factor signal. Our study engenders a comprehensive framework for the intricate examination of pTyr protein complexes and presents, for the foremost occasion, a quantitative landscape delineating the composition of pTyr protein complexes in HeLa cells.

Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses.

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Preoperative Survival Prediction in Intrahepatic Cholangiocarcinoma Using an Ultrasound-Based Radiographic-Radiomics Signature.

OBJECTIVES: To construct a preoperative model for survival prediction in intrahepatic cholangiocarcinoma (ICC) patients using ultrasound (US) based radiographic-radiomics signatures. METHODS: Between April 2010 and September 2015, 170 patients with ICC who underwent curative resection were retrospectively recruited. Overall survival (OS)-related radiographic signatures and radiomics signatures based on preoperative US were built and assessed through a time-dependent receiver operating characteristic curve analysis. A nomogram was developed based on the selected predictors from the radiographic-radiomics signatures and clinical and laboratory results of the training cohort (n = 127), validated in an independent testing cohort (n = 43) by the concordance index (C-index), and compared with the Tumor Node Metastasis (TNM) cancer staging system as well as the radiographic and radiomics nomograms. RESULTS: The median areas under the curve of the radiomics signature and radiographic signature were higher than that of the TNM staging system in the testing cohort, although the values were not significantly different (0.76-0.82 versus 0.62, P = .485 and .264). The preoperative nomogram with CA 19-9, sex, ascites, radiomics signature, and radiographic signature had C-indexes of 0.72 and 0.75 in the training and testing cohorts, respectively, and it had significantly higher predictive performance than the 8th TNM staging system in the testing cohort (C-index: 0.75 versus 0.67, P = .004) and a higher C-index than the radiomics nomograms (0.75 versus 0.68, P = .044). CONCLUSIONS: The preoperative nomogram integrated with the radiographic-radiomics signature demonstrated good predictive performance for OS in ICC and was superior to the 8th TNM staging system.

Contrast-Enhanced Ultrasound-Based Nomogram: A Potential Predictor of Individually Postoperative Early Recurrence for Patients With Combined Hepatocellular-Cholangiocarcinoma.

PURPOSES: To evaluate the postsurgical prognostic implication of contrast-enhanced ultrasound (CEUS) for combined hepatocellular-cholangiocarcinoma (CHC). To build a CEUS-based early recurrence prediction classifier for CHC, in comparison with tumor-node-metastasis (TNM) staging. METHODS: The CEUS features and clinicopathological findings of each case were analyzed, and the Liver Imaging Reporting and Data System categories were assigned. The recurrence-free survival associated factors were evaluated by Cox proportional hazard model. Incorporating the independent factors, nomograms were built to estimate the possibilities of 3-month, 6-month, and 1-year recurrence and whose prognostic value was determined by time-dependent receiver operating characteristics, calibration curves, and hazard layering efficiency validation, comparing with TNM staging system. RESULTS: In the multivariable analysis, the levels of carbohydrate antigen 19-9, prothrombin time and total bilirubin, and tumor shape, the Liver Imaging Reporting and Data System category were independent factors for recurrence-free survival. The LR-M category showed longer recurrence-free survival than did the LR-4/5 category. The 3-month, 6-month, and 1-year area under the curves of the CEUS-clinical nomogram, clinical nomogram, and TNM staging system were 0.518, 0.552, and 0.843 versus 0.354, 0.240, and 0.624 (P = .048, .049, and .471) vs. 0.562, 0.545, and 0.843 (P = .630, .564, and .007), respectively. The calibration curves of the CEUS-clinical model at different prediction time pionts were all close to the ideal line. The CEUS-clinical model effectively stratified patients into groups of high and low risk of recurrence in both training and validation set, while the TNM staging system only works on the training set. CONCLUSIONS: Our CEUS-clinical nomogram is a reliable early recurrence prediction tool for hepatocellular-cholangiocarcinoma and helps postoperative risk stratification.

Kinesin family member 2C aggravates the progression of hepatocellular carcinoma and interacts with competing endogenous RNA.

Kinesin family member 2C (KIF2C), a substantial mitotic regulator, has been verified to exert a malignant function in several cancers. However, its function in hepatocellular carcinoma (HCC) remains unclear. In this study, the expression profile of KIF2C in HCC was characterized through the dataset from the TCGA and clinical tissue microarrays containing 220 pairs of resected HCC tissues and adjacent nontumor tissues in our hospital. The results indicated that KIF2C was substantially higher expression in tumor tissues than adjacent nontumor tissues. High expression of KIF2C significantly correlated with large tumor (>5.0 cm) (P = .001) and implied a dismal postoperative overall survival (OS) (hazard ratio [HR] = 1.729; P = .002) in our cohort of patients. Gain and loss of function assays displayed that KIF2C promoted HCC cell proliferation, accelerated cell cycle progression, and impeded apoptosis. By bioinformatic tools and mechanistic investigation, we found that KIF2C interacted with various cell-cycle-related proteins and was significantly involved in growth-promoting pathways. KIF2C upregulated PCNA and CDC20 expression. Subsequently, we investigated the regulation of KIF2C by competing endogenous RNA and elucidated that has-miR-6715a-3p was directly bond to the 3'-untranslated region of KIF2C through dual luciferase assays, thereby inhibiting KIF2C expression. Furthermore, the long noncoding RNA GS1-358P8.4 was found to be a candidate of KIF2C for has-miR-6715a-3p binding. HCC patients with high lncRNA-GS1-358P8.4 expression had shorter OS and relapse-free survival compared to those with low expression, which was accordance with the KIF2C. Taken together, KIC2C aggravated HCC progression, it could serve as a prognostic indicator and confer a novel target for clinical treatment.

Dirac Polarons and Resistivity Anomaly in ZrTe_{5} and HfTe_{5}.

Resistivity anomaly, a sharp peak of resistivity at finite temperatures, in the transition-metal pentatellurides ZrTe_{5} and HfTe_{5} was observed four decades ago, and more exotic and anomalous behaviors of electric and thermoelectric transport were revealed in recent years. Here, we present a theory of Dirac polarons, composed by massive Dirac electrons and holes in an encircling cloud of lattice displacements or phonons at finite temperatures. The chemical potential of Dirac polarons sweeps the band gap of the topological band structure by increasing the temperature, leading to the resistivity anomaly. Formation of a nearly neutral state of Dirac polarons accounts for the anomalous behaviors of the electric and thermoelectric resistivity around the peak of resistivity.

Anomalous Temperature Dependence of Quantum Correction to the Conductivity of Magnetic Topological Insulators.

Quantum transport in magnetic topological insulators reveals a strong interplay between magnetism and topology of electronic band structures. A recent experiment on magnetically doped topological insulator Bi_{2}Se_{3} thin films showed the anomalous temperature dependence of the magnetoconductivity while their field dependence presents a clear signature of weak antilocalization [Tkac et al., Phys. Rev. Lett. 123, 036406 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.036406]. Here, we demonstrate that the tiny mass of the surface electrons induced by the bulk magnetization leads to a temperature-dependent correction to the π Berry phase and generates a decoherence mechanism to the phase coherence length of the surface electrons. As a consequence, the quantum correction to conductivity can exhibit nonmonotonic behavior by decreasing the temperature. This effect is attributed to the close relation of the Berry phase and quantum interference of the topological surface electrons in quantum topological materials.

Topological Phase Transitions in Disordered Electric Quadrupole Insulators.

We investigate disorder-driven topological phase transitions in quantized electric quadrupole insulators in two dimensions. We show that chiral symmetry can protect the quantization of the quadrupole moment q_{xy}, such that the higher-order topological invariant is well defined even when disorder has broken all crystalline symmetries. Moreover, nonvanishing q_{xy} and consequent corner modes can be induced from a trivial insulating phase by disorder that preserves chiral symmetry. The critical points of such topological phase transitions are marked by the occurrence of extended boundary states even in the presence of strong disorder. We provide a systematic characterization of these disorder-driven topological phase transitions from both bulk and boundary descriptions.

Route to Rheumatoid Arthritis by Macrophage-Derived Microvesicle-Coated Nanoparticles.

The targeted delivery of therapeutics to sites of rheumatoid arthritis (RA) has been a long-standing challenge. Inspired by the intrinsic inflammation-targeting capacity of macrophages, a macrophage-derived microvesicle (MMV)-coated nanoparticle (MNP) was developed for targeting RA. The MMV was efficiently produced through a novel method. Cytochalasin B (CB) was applied to relax the interaction between the cytoskeleton and membrane of macrophages, thus stimulating MMV secretion. The proteomic profile of the MMV was analyzed by iTRAQ (isobaric tags for relative and absolute quantitation). The MMV membrane proteins were similar to those of macrophages, indicating that the MMV could exhibit bioactivity similar to that of RA-targeting macrophages. A poly(lactic- co-glycolic acid) (PLGA) nanoparticle was subsequently coated with MMV, and the inflammation-mediated targeting capacity of the MNP was evaluated both in vitro and in vivo. The in vitro binding of MNP to inflamed HUVECs was significantly stronger than that of the red blood cell membrane-coated nanoparticle (RNP). Compared with bare NP and RNP, MNP showed a significantly enhanced targeting effect in vivo in a collagen-induced arthritis (CIA) mouse model. The targeting mechanism was subsequently revealed according to the proteomic analysis, indicating that Mac-1 and CD44 contributed to the outstanding targeting effect of the MNP. A model drug, tacrolimus, was encapsulated in MNP (T-RNP) and significantly suppressed the progression of RA in mice. The present study demonstrates MMV as a promising and rich material, with which to mimic macrophages, and demonstrates that MNP is an efficient biomimetic vehicle for RA targeting and treatment.

Quantum Interference Theory of Magnetoresistance in Dirac Materials.

Magnetoresistance in many samples of Dirac semimetals and topological insulators displays nonmonotonic behavior over a wide range of magnetic fields. Here a formula of magnetoconductivity is presented for massless and massive Dirac fermions in Dirac materials due to quantum interference of Dirac fermions in scalar impurity scattering potentials. It reveals a striking crossover from positive to negative magnetoresistivity, uncovering strong competition between weak localization and weak antilocalization in multiple Cooperon channels at different chemical potentials, effective masses, and finite temperatures. This work sheds light on the important role of strong coupling of the conduction and valence bands in the quantum interference transport in topological nontrivial and trivial Dirac materials.

Comparison between M-score and LR-M in the reporting system of contrast-enhanced ultrasound LI-RADS.

OBJECTIVE: To develop a contrast-enhanced ultrasound (CEUS) M-score and compare it with LR-M in CEUS Liver Imaging Reporting and Data System (LI-RADS). METHODS: We retrospectively enrolled 105 consecutive high-risk patients with hepatocellular carcinoma (HCC) and 105 with intrahepatic cholangiocarcinoma (ICC). The subjects were selected by propensity score matching between November 2003 and December 2017. A CEUS M-score for predicting ICC was constructed based on specific CEUS features by the least absolute shrinkage and selection operator regularised regression. M-score was used to develop a modified CEUS LI-RADS. The diagnostic performance of the modified CEUS LI-RADS using M-score for diagnosing HCC and ICC was compared with American College of Radiology (ACR) CEUS LI-RADS using LR-M. RESULTS: The most useful features for ICC were as follows: poorly circumscribed (69.52%), rim enhancement (63.81%), early washout (92.38%), intratumoural vein (56.19%), obscure boundary of intratumoural non-enhanced area (57.14%), and marked washout (59.05%, all p < 0.001). For predicting ICC, the M-score had a higher specificity (88.57% vs. 63.81%) with lower sensitivity (89.52% vs. 95.24%) compared with LR-M. For diagnosing HCC, the sensitivity of modified LI-RADS (80.95%) was much higher than that of ACR LI-RADS (57.14%), but the specificity was lower (90.48% vs. 96.19%). The area under the curve (AUC) of modified LI-RADS (0.857) was much higher than that of ACR LI-RADS (0.767, p = 0.0001). The modified positive predictive value (PPV) of ACR LI-RADS and modified LI-RADS were 99.42% and 98.99%, respectively. CONCLUSIONS: The modified LI-RADS with M-score had higher sensitivity for diagnosing HCC and higher specificity for diagnosing ICC than ACR LI-RADS. KEY POINTS: • For predicting ICC, the M-score had a higher specificity (88.57% vs. 63.81%) with lower sensitivity (89.52% vs. 95.24%) compared with LR-M. • A CEUS M-score for predicting ICC consisted of more detailed CEUS features (poorly circumscribed, rim enhancement, early washout, intratumoural vein, obscure boundary of intratumoural non-enhanced area, and marked washout) was constructed. • For diagnosing HCC, the sensitivity of modified LI-RADS (80.95%) was much higher than that of ACR LI-RADS (57.14%), but the specificity was lower (90.48% vs. 96.19%). The modified positive predictive value (PPV) of ACR LI-RADS and modified LI-RADS were 99.42% and 98.99%, respectively.

Hornerin promotes tumor progression and is associated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study. METHODS: The expression levels of HRNR were assessed in tumor samples from a cohort of 271 HCC patients. The effect of HRNR on proliferation, colony formation and invasion of tumor cells was examined. We further determined the role of HRNR in tumor growth in vivo by using xenograft HCC tumor models. The possible mechanism of the HRNR promotion of HCC progression was explored. RESULTS: We found that HRNR was overexpressed in HCC tissues. The high expression of HRNR in HCCs was significantly associated with vascular invasion, poor tumor differentiation, and advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of HCC patients with high HRNR expression were poorer than those in the low HRNR expression group. HRNR expression was an independent risk factor linked to both poor DFS (HR = 2.209, 95% CI = 1.627-2.998,P <  0.001) and OS (HR = 2.459,95% CI = 1.736-3.484, P <  0.001). In addition, the knockdown of HRNR by shRNAs significantly inhibited the proliferation, colony formation, migration and invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing in a xenograft model of HCC. CONCLUSIONS: HRNR promotes tumor progression and is correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via the regulation of the AKT pathway.

Low expression of c-Myc protein predicts poor outcomes in patients with hepatocellular carcinoma after resection.

BACKGROUND: Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-ß) signaling cascade. Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-ß signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-ß signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis. However, the prognostic significance of c-Myc in HCC is less understood METHODS: The expression of c-Myc protein and mRNA were measured by immunohistochemistry (IHC) and qRT- PCR, respectively. IHC was performed to detect TGF-ß1 and ELF expression in HCC tissues. Their relationship with clinicopathological factors and overall survival (OS) and disease free survival (DFS) were examined. RESULTS: The expression of c-Myc protein and mRNA in HCC tissues were significantly higher in HCC area than those in normal liver tissues. However, the expression were low compared with those adjacent to HCC area. c-Myc protein was independently predictive of DFS and OS, and it was negatively correlated with tumor size (P = 0.031), tumor number (P = 0.038), and recurrence (P = 0.001). Low c-Myc expression was associated with short-term recurrence and poor prognosis. The predictive value of c-Myc combined with TGF-ß1 or/and ELF was higher than that of any other single marker. Low c-Myc, high TGF-ß1 or/and low ELF expression was associated with the worst DFS and OS. CONCLUSIONS: Low expression of c-Myc protein predicts poor outcomes in patients with HCC with hepatectomy. The combination of the expression of c-Myc, TGF-ß1, and ELF can be used to accurately predict outcomes of patients with HCC.

BQ123 selectively improved tumor perfusion and enhanced nanomedicine delivery for glioblastomas treatment.

Blood perfusion was always lower in tumor tissues as compared with that in surrounding normal tissues which lead to inadequate nanomedicine delivery to tumors. Inspired by the upregulation of both endothelin-1 (ET1) and its ETA receptor in tumor tissues and the crucial contribution of ET1-ETA receptor signaling to maintain myogenic tone of tumor vessels, we supposed that inhibition of ET1-ETA receptor signaling might selectively improve tumor perfusion and help deliver nanomedicine to tumors. Using human U87 MG glioblastomas with abundant vessels as the tumor model, immunofluorescence staining demonstrated that ETA receptor was overexpressed by in glioblastomas tissues compared with normal brain tissues. A single administration of ETA receptor antagonist BQ123 at the dose of 0.5 mg/kg could effectively improve tumor perfusion which was evidenced by in vivo photoacoustic imaging. Additionally, a single treatment of BQ123 could significantly improve the accumulation of nanoparticles (NPs) around 115 nm in tumors with a more homogeneous distribution pattern by in vivo imaging, ex vivo imaging as well as in vivo distribution experiments. Furthermore, BQ123 successfully increased the therapeutic benefits of paclitaxel-loaded NPs and significantly elongated the survival time of orthotropic glioblastomas-bearing animal models. In summary, the present study provided a new strategy to selectively improve tumor perfusion and therefore benefit nanomedicine delivery for tumor therapy. As ET1-ETA receptor signaling was upregulated in a variety of tumors, this strategy might open a new avenue for tumor treatment.

Non-Invasive Diagnostic Criteria for Hepatocellular Carcinoma in Hepatitis B Virus-Endemic Areas: Is Cirrhosis Indispensable?

AIM: To confirm whether cirrhosis is indispensable for the non-invasive diagnostic criteria for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-endemic areas. METHODS: Between January 2014 and December 2014, a total of 409 patients with pathologically proven focal liver lesions who underwent contrast-enhanced ultrasound (CEUS) were recruited from our institution. Clinical liver cirrhosis, HBV/HCV infection and HCC-typical vascular pattern of the targeted lesion on CEUS were evaluated. The following 3 criteria were applied to these patients to diagnose HCC: criterion 1, clinical liver cirrhosis and HCC-typical vascular pattern; criterion 2, HBV/HCV infection and HCC-typical vascular pattern; criterion 3, HBV/HCV infection or clinical liver cirrhosis and HCC-typical vascular pattern. Pathological reports were considered the gold standard. RESULTS: A total of 311 patients had confirmed HCC by pathology. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and area under the ROC curve for criterion 1 were 29.6, 90.8, 44.3, 91.1, 28.9, and 0.60% respectively. For criterion 2, they were 83.3, 74.5, 81.2, 91.2, 58.4, and 0.79%, respectively, and for criterion 3, they were 86.2, 72.5, 82.9, 90.9, 62.3, and 0.79% respectively. CONCLUSIONS: In HBV-endemic areas, when using the HBV/HCV infection instead of cirrhosis as the precondition of the non-invasive diagnostic criteria for HCC, we should be aware of the potential false positive. Cirrhosis still plays an important role in the non-invasive diagnostic criteria for HCC because of the high specificity.

Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.

Anomalous Phase Shift of Quantum Oscillations in 3D Topological Semimetals.

Berry phase physics is closely related to a number of topological states of matter. Recently discovered topological semimetals are believed to host a nontrivial π Berry phase to induce a phase shift of ±1/8 in the quantum oscillation (+ for hole and - for electron carriers). We theoretically study the Shubnikov-de Haas oscillation of Weyl and Dirac semimetals, taking into account their topological nature and inter-Landau band scattering. For a Weyl semimetal with broken time-reversal symmetry, the phase shift is found to change nonmonotonically and go beyond known values of ±1/8 and ±5/8, as a function of the Fermi energy. For a Dirac semimetal or paramagnetic Weyl semimetal, time-reversal symmetry leads to a discrete phase shift of ±1/8 or ±5/8. Different from the previous works, we find that the topological band inversion can lead to beating patterns in the absence of Zeeman splitting. We also find the resistivity peaks should be assigned integers in the Landau index plot. Our findings may account for recent experiments in Cd_{2}As_{3} and should be helpful for exploring the Berry phase in various 3D systems.

A novel and accurate predictor of survival for patients with hepatocellular carcinoma after surgical resection: the neutrophil to lymphocyte ratio (NLR) combined with the aspartate aminotransferase/platelet count ratio index (APRI).

BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) depends largely on such non-tumor factors as inflammatory condition, immune state, viral infection and liver fibrosis. Various inflammation-based prognostic scores have been associated with survival in patients with HCC, such as the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and the prognostic nutritional index (PNI). The aspartate aminotransferase/platelet count ratio index (APRI) is thought to be a biomarker of liver fibrosis and cirrhosis. This study aims to evaluate the ability of these indices to predict survival in HCC patients after curative hepatectomy, and probe the increased prognostic accuracy of APRI combined with established inflammation-based prognostic scores. METHODS: Data were collected retrospectively from 321 patients who underwent curative resection for HCC. Preoperative NLR, PLR, PNI, APRI and clinico-pathological variables were analyzed. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Univariate analysis showed that NLR, PLR, PNI and APRI were significantly associated with DFS and OS in HCC patients with curative resection. Multivariate analysis showed that NLR and APRI were superior to PLR and PNI, and both were independently correlated with DFS and OS. Preoperative NLR >2 or APRI >1.68 predicted poor prognosis of patients with HCC after hepatectomy. Furthermore, the predictive range of NLR combined with APRI was more sensitive than that of either measure alone. CONCLUSIONS: Preoperative NLR and APRI are independent predictors of DFS and OS in patients with HCC after surgical resection. Higher levels of NLR or APRI predict poorer outcomes in HCC patients. Intriguingly, combining NLR and APRI increases the prognostic accuracy of testing.

Adjuvant antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after curative treatment: A systematic review and meta-analysis.

AIM: To investigate whether adjuvant antiviral treatment could improve prognosis and entecavir is the optimal nucleoside/nucleotide analog (NA) regimen after curative therapy of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A comprehensive electronic search was performed. All controlled trials comparing antiviral treatment with placebo or no treatment for HBV-related HCC after curative treatment were included. The pooled hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Stata 12.0 software. An indirect treatment comparison method was used to compare the relative efficacy of different NA strategies. RESULTS: Twenty-one studies containing 8072 patients were included. NA was found to significantly improve recurrence-free survival (RFS) and overall survival (OS). Alternatively, for interferon, a non-significant benefit was found. By adjusted indirect comparisons among entecavir, lamivudine and adefovir, entecavir were found to display almost but not significant superiority to the other NA in improving RFS. No tendency favoring a specific NA regimen was found for OS. CONCLUSION: In HBV-HCC patient after curative treatment, NA improve the prognosis significantly but the role of interferon remains to be elucidated; entecavir was not found to be superior to other NA based on available data.

Electrically tunable in-plane anisotropic magnetoresistance in topological insulator BiSbTeSe2 nanodevices.

We report tunable in-plane anisotropic magnetoresistance (AMR) in nanodevices based on topological insulator BiSbTeSe2 (BSTS) nanoflakes by electric gating. The AMR can be changed continuously from negative to positive when the Fermi level is manipulated to cross the Dirac point by an applied gate electric field. We also discuss effects of the gate electric field, current density, and magnetic field on the in-plane AMR with a simple physical model, which is based on the in-plane magnetic field induced shift of the spin-momentum locked topological two surface states that are coupled through side surfaces and bulk weak antilocalization (WAL). The large, tunable and bipolar in-plane AMR in BSTS devices provides the possibility of fabricating more sensitive logic and magnetic random access memory AMR devices.