Cathodoluminescence Nanoscopy: State of the Art and Beyond.

Cathodoluminescence (CL) nanoscopy is proven to be a powerful tool to explore nanoscale optical properties, whereby free electron beams achieve a spatial resolution far beyond the diffraction limit of light. With developed methods for the control of electron beams and the collection of light, the dimension of information that CL can access has been expanded to include polarization, momentum, and time, holding promise to provide invaluable insights into the study of materials and optical near-field dynamics. With a focus on the burgeoning field of CL nanoscopy, this perspective outlines the recent advancements and applications of this technique, as illustrated by the salient experimental works. In addition, as an outlook for future research, several appealing directions that may bring about developments and discoveries are highlighted.

A novel prognostic scoring system to predict portal vein tumor thrombosis in patients with hepatitis B virus-associated hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is associated with a poor prognosis for HCC patients. Herein we aimed to establish a scoring system to predict the risk of PVTT formation in hepatitis B virus (HBV)-associated HCC. METHODS: A total of 848 patients from the Henan Province Traditional Chinese Medicine (TCM) Hospital with HCC were included in the study. Among them, 403 with and 445 without PVTT were retrospectively analyzed to identify the risk factors for PVTT formation, using a novel scoring system to predict the occurrence of PVTT in HBV-associated HCC patients. The scoring system was validated using clinical data from the First Affiliated Hospital of Henan University of TCM. Significant findings: The Cox proportional-hazard regression model revealed that gender, tumor size, the neutrophil-lymphocyte ratio, and alpha-fetoprotein and C-reactive protein concentrations were dependent clinical prognostic factors for PVTT, which were included in the final scoring model for PVTT prediction (AUC, 0.858; 95% CI: 0.832 to 0.881). The scoring model ranked HCC patients into 3 risk grades. A sensitivity analysis for validation of the scoring system was performed on 489 patients with HBV-related HCC. The proportion of patients in each grade was not significantly different. CONCLUSIONS: The study established a risk warning system for PVTT prediction in HCC patients. More substantial clinical data will be necessary to confirm these findings.

Electron-Induced Chirality-Selective Routing of Valley Photons via Metallic Nanostructure.

Valleytronics in 2D transition metal dichalcogenides has raised a great impact in nanophotonic information processing and transport as it provides the pseudospin degree of freedom for carrier control. The imbalance of carrier occupation in inequivalent valleys can be achieved by external stimulations such as helical light and electric field. With metasurfaces, it is feasible to separate the valley exciton in real space and momentum space, which is significant for logical nanophotonic circuits. However, the control of valley-separated far-field emission by a single nanostructure is rarely reported, despite the fact that it is crucial for subwavelength research of valley-dependent directional emission. Here, it is demonstrated that the electron beam permits the chirality-selective routing of valley photons in a monolayer WS2 with Au nanostructures. The electron beam can locally excite valley excitons and regulate the coupling between excitons and nanostructures, hence controlling the interference effect of multipolar electric modes in nanostructures. Therefore, the separation degree can be modified by steering the electron beam, exhibiting the capability of subwavelength control of valley separation. This work provides a novel method to create and resolve the variation of valley emission distribution in momentum space, paving the way for the design of future nanophotonic integrated devices.

Phonon-assisted upconversion in twisted two-dimensional semiconductors.

Phonon-assisted photon upconversion (UPC) is an anti-Stokes process in which incident photons achieve higher energy emission by absorbing phonons. This letter studies phonon-assisted UPC in twisted 2D semiconductors, in which an inverted contrast between UPC and conventional photoluminescence (PL) of WSe2 twisted bilayer is emergent. A 4-fold UPC enhancement is achieved in 5.5° twisted bilayer while PL weakens by half. Reduced interlayer exciton conversion efficiency driven by lattice relaxation, along with enhanced pump efficiency resulting from spectral redshift, lead to the rotation-angle-dependent UPC enhancement. The counterintuitive phenomenon provides a novel insight into a unique way that twisted angle affects UPC and light-matter interactions in 2D semiconductors. Furthermore, the UPC enhancement platform with various superimposable means offers an effective method for lighting bilayers and expanding the application prospect of 2D stacked van der Waals devices.

Nek2B accelerates the progression of hepatocellular carcinoma through regulating SFRP1 to activate the Wnt/ß-catenin pathway.

PURPOSE: The purpose of this study was to clarify the expression pattern of Nek2B in hepatocellular carcinoma (HCC) and its influence on malignant phenotypes of HCC through regulating SFRP1 and the Wnt/ß-catenin pathway. METHODS: Nek2B levels in 64 paired HCC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between Nek2B level and clinical parameters of HCC patients was analyzed. Regulatory effects of Nek2B and SFRP1 on clonality, proliferation and apoptosis of MHCC97H and Hep3B cells were determined through functional experiments. Western blot was conducted to detect protein levels of SFRP1, ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells with overexpression or knockdown of Nek2B. At last, rescue experiments were performed to clarify the role of Nek2B/SFRP1 regulatory loop in aggravating the progression of HCC. RESULTS: Nek2B was upregulated in HCC tissues and cells. HCC patients expressing a high level of Nek2B were in more advanced tumor stage and had worse prognosis. Overexpression of Nek2B in MHCC97H cells enhanced clonality, 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio and suppressed apoptosis. Besides, knockdown of Nek2B in Hep3B cells yielded the opposite results. SFRP1 was downregulated in HCC, and low level of SFRP1 predicted worse prognosis of HCC. Overexpression of Nek2B downregulated SFRP1, but upregulated ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells. Importantly, Nek2B/SFRP1 regulatory loop was identified to aggravate the progression of HCC. CONCLUSIONS: Nek2B is upregulated in HCC, and closely linked to tumor stage and poor prognosis in HCC patients. Through interaction with SFRP1, Nek2B aggravates the progression of HCC by activating the Wnt/ß-catenin pathway.

Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

Background/Aims: Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods: We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results: Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions: ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.

PD-1+ TIGIT+ CD8+ T cells are associated with pathogenesis and progression of patients with hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) is usually considered an inflammation-related cancer associated with chronic inflammation triggered by exposure to HBV and tumor antigens. T-cell exhaustion is implicated in immunosuppression of chronic infections and tumors. Although immunotherapies that enhance immune responses by targeting programmed cell death-1(PD-1)/PD-L1 are being applied to malignancies, these treatments have shown limited response rates, suggesting that additional inhibitory receptors are also involved in T-cell exhaustion and tumor outcome. Here, we analyzed peripheral blood samples and found that coexpression of PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) was significantly upregulated on CD4+ and CD8+ T cells from patients with HBV-HCC compared with those from patients with chronic HBV or HBV-liver cirrhosis. Additionally, PD-1+ TIGIT+ CD8+ T-cell populations were elevated in patients with advanced stage and progressed HBV-HCC. Importantly, PD-1+ TIGIT+ CD8+ T-cell populations were negatively correlated with overall survival rate and progression-free survival rates. Moreover, we showed that PD-1+ TIGIT+ CD8+ T cells exhibit features of exhausted T cells, as manifested by excessive activation, high expression of other inhibitory receptors, high susceptibility to apoptosis, decreased capacity for cytokine secretion, and patterns of transcription factor expression consistent with exhaustion. In conclusion, PD-1+ TIGIT+ CD8+ T-cell populations are associated with accelerated disease progression and poor outcomes in HBV-HCC, which might not only have important clinical implications for prognosis but also provide a rationale for new targets in immunotherapy.

Impact of gender as a prognostic factor in HBV-related Hepatocellular Carcinoma: the survival strength of female patients in BCLC stage 0-B.

Background and Aims: Although previous studies suggested that female patients who underwent curative resection in early-stage hepatocellular carcinoma (HCC) had better survival rates than male patients, it is unclear whether females in different HCC stages actually have survival advantage. This study aimed to investigate whether gender differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contributed to different survival outcomes in hepatitis B virus (HBV)-related HCC. Methods: A retrospective analysis was performed of 1,753 patients diagnosed with HBV-related HCC between January 2008 and June 2017 at the Beijing Ditan hospital. The BCLC stages were classified into BCLC stage 0-B and BCLC stage C-D groups. Factors determining overall survival (OS) and progression-free survival (PFS) were analyzed via univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional-hazards regression models. Results: The cohort consisted of 1,202 BCLC stage 0-B and 551 BCLC stage C-D HBV-related HCC patients. Gender was identified to be an independent risk factor for OS (HR = 0.617; 95% CI, 0.426-0.895; p = 0.011) and PFS (HR = 0.728; 95% CI, 0.558-0.950; p = 0.019) in BCLC stage 0-B HBV-related HCC patients. With respect to OS and PFS, there were significant differences between female and male patients only in BCLC stage 0-B, but not in BCLC stage C-D. The OS and PFS in BCLC stage 0-B for female patients was significantly greater than that for male patients (p = 0.0103, p = 0.0112). Tumor multiplicity and size were independent risk factors for female patients in BCLC stage 0-B, whereas tumor multiplicity, tumor size, HBV-DNA, hemoglobin, total bilirubin, and alpha-fetoprotein levels were independent risk factors for male patients in BCLC stage 0-B. Conclusions: Different outcomes in OS or PFS with respect to gender only exist in BCLC stage 0-B HBV-related HCC patients. Female patients have a better outcome than male patients in BCLC stage 0-B.

Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma.

BACKGROUND: Many patients with hepatocellular carcinoma (HCC) in Asian countries seek adjuvant therapy with traditional Chinese medicine (TCM). This study aims to explore the benefits of TCM therapy in the long-term survival of patients with hepatocellular carcinoma in China. PATIENTS AND METHODS: In total, 3483 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled in this study. We used 1:1 frequency matching by sex, age, diagnosis time, Barcelona Clinic Liver Cancer staging, and type of treatments to compare the TCM users (n = 526) and non-TCM users (n = 526). A Cox multivariate regression model was employed to evaluate the effects of TCM therapy on the HR value and Kaplan-Meier survival curve for mortality risk in HCC patients. A log-rank test was performed to analyze the effect of TCM therapy on the survival time of HCC patients. RESULTS: The Cox multivariate analysis indicated that TCM therapy was an independent protective factor for 5-year survival in patients with HCC (adjusted HR = 0.46, 95% CI 0.40-0.52, p < 0.0001). The Kaplan-Meier curve also showed that after PS matching, TCM users had a higher overall survival rate and a higher progression-free survival rate than non-TCM users. TCM users, regardless of the classification of etiology, tumor stage, liver function level, or type of treatment, all benefited significantly from TCM therapy. In addition, it was found that the most commonly used Chinese patent medications are Fufang Banmao Capsule, Huaier Granule, and Jinlong Capsule. CONCLUSION: Using traditional Chinese medications as adjuvant therapy can probably prolong median survival time and improve the overall survival among patients with HCC. Further scientific studies and clinical trials are needed to examine the efficiency and safety.

Comparative effectiveness and safety of traditional Chinese medicine supporting Qi and enriching blood for cancer related anemia in patients not receiving chemoradiotherapy: a meta-analysis and systematic review.

A systematic review and meta-analysis of previous randomized controlled trials of traditional Chinese medicine (TCM) supporting Qi and enriching blood in the treatment of cancer related anemia (CRA) in patients not receiving chemoradiotherapy were conducted. A total of 13 randomized controlled trials were included. Compared with the control group, better improvement was found for the level of hemoglobin (mean difference=4.57, 95% CI [1.38, 7.76], P=0.005) and overall therapeutic effect (risk ratio [RR]=1.31, 95% CI [1.18, 1.46], P<0.000) in the TCM groups. The incidence of related adverse events was not increased in the TCM groups (RR=0.54, 95% CI [0.29, 0.99], P=0.05). However, due to the relatively low quality and the small sample sizes of the included studies, the results should be interpreted with a degree of caution. Nevertheless, TCM with the role of supporting Qi and enriching blood may be a safe and effective treatment for CRA in patients not receiving chemoradiotherapy and might be considered as an alternative treatment to conventional western medicine including iron supplements and erythropoietin.

Association and interaction between model for end-stage liver disease score and minimally invasive treatment with regard to mortality of patients with hepatitis B virus-associated hepatocellular carcinoma and portal vein tumor thrombi.

The development of minimally invasive treatment over the last two decades has had a great impact on hepatitis B virus (HBV)-associated primary liver cancer. The model for end-stage liver disease (MELD) score is the optimal evaluated parameter for mortality in patients with end-stage liver disease. However, the association between MELD score and minimally invasive treatment with regard to the mortality of patients with HBV-associated hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT) remains unclear. In the present study, a total of 173 patients who had been diagnosed with HBV-associated HCC and PVTT in the Beijing Ditan Hospital (Beijing, China), between January 2012 and January 2015, were screened. Follow-up was performed to observe the survival time and collect information on the demographic characteristics and associated clinical indicators present in the cohort. The patient's age, sex, laboratory parameters and the use of minimally invasive treatment were analyzed with SPSS 20.0 software. Independent risk factors for mortality were screened by Cox regression analysis. Logistic regression indicated that there was an interaction between the MELD score and minimally invasive treatment. In addition, a MELD score ≤17.85 was associated with a lower mortality rate subsequent to minimally invasive treatment.

Effect of serum triglyceride level on the prognosis of patients with hepatocellular carcinoma in the absence of cirrhosis.

BACKGROUND: The liver plays an important role in the metabolism of lipid and lipoprotein. Dyslipidemia has been demonstrated to be related with several cancers, but the association between serum lipid and hepatocellular carcinoma (HCC) in the absence of cirrhosis remains unclear. METHODS: A total of 2528 patients with HCC at the Beijing Ditan Hospital between February 2008 and December 2017 were retrospectively included in the study. We identified 200 patients with HCC without cirrhosis by histopathology, imaging, endoscopic findings, and laboratory tests. Multivariate regression analysis was performed to determine the independent characteristics associated with HCC without cirrhosis and its prognosis. RESULTS: In the logistics regression analysis, compared to patients with HCC with cirrhosis, patients with HCC without cirrhosis were more likely to have elevated triglyceride (TG) levels (OR = 2.66; 95% CI, 1.18-6.01; P = 0.019). The Kaplan-Meier analysis revealed that a lower TG level was a risk factor regardless of the presence of cirrhosis. The results of the Cox proportional hazard regression analysis showed that a decreased TG level was significantly related to a worse overall survival (HR = 0.51; 95% CI, 0.29-0.89; P = 0.017). CONCLUSION: Serum TG level may be an independent factor to predict the prognosis of patients with HCC in the absence of cirrhosis.

A novel scoring model for predicting mortality risk in patients with cirrhosis and hepatorenal syndrome.

BACKGROUND AND AIMS: This study aimed to create a risk scoring model for death from cirrhosis and hepatorenal syndrome, improve the detection rate of high-risk groups, and provide clinical evidence for early intervention treatment. PATIENTS AND METHODS: We retrospectively recruited 196 patients with cirrhosis and hepatorenal syndrome between 1 January 2013 and 31 July 2014 at Beijing Ditan Hospital, Capital Medical University, China. The clinical information, biochemical values, age, and sex of the patients were included in the multivariate logistic regression model for screening independent risk factors. The model was validated in 56 patients with cirrhosis and hepatorenal syndrome between 1 August 2014 and 31 December 2014 at Beijing Ditan Hospital, Capital Medical University, China. RESULTS: The death risk prediction scoring model included the following four independent risk factors: liver cancer, neutrophil above 70%, alanine aminotransferase higher than 40 U/l, and creatinine higher than 127 mmol/l. The sum death risk score ranged from 0 to 5: 0-2 identified patients with a lower risk of death (mortality rates: 12-41.4%), whereas 3-5 identified patients with a higher risk of death (mortality rates: 48.8-80%). Receiver-operating characteristic curves were constructed for the scoring model and the areas under the curves (AUC) were compared using the z-test. The AUC of the scoring model was 0.843. In addition, the AUC of validated model in 56 patients was 0.742. CONCLUSION: The scoring model can accurately predict mortality risk in patients with hepatorenal syndrome.