Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.

A quantitative comparison of five optical coherence tomography angiography systems in clinical performance

AIM： To compare the clinical performance of 4 spectraldomain（SD） optical coherence tomography angiography（OCTA） systems： AngioVueTM, AngioPlexTM, Spectralis？ OCTA, AngioScan, and 1 swept-source（SS） OCTA SS OCT AngioTM. METHODS： Twenty-seven undilated right eyes of 27 participants underwent OCTA examination using five different systems respectively for both 3×3 and 6×6 mm^2 scan pattern（Spectralis OCTA for 3×3 mm^2 scan only）. Image quality, including vessel valid visibility and the number of motion artifacts, and acquisition time were evaluated. Repeated measures analysis of variance（ANOVA） with Bonferroni＇s post-test and Friedman test with Dunn＇s posttest were used to compare measurements.RESULTS： The age of the subjects was 28.19±5.55 y（range, 23-49 y）. The spherical equivalent refraction was-2.55±1.84 D（range, 0.00 to-5.25 D）. Significant difference was observed in the evaluation of vessel valid visibility（Angio Vue the highest： 0.111±0.031 for 3×3 mm^2 scan and 0.128±0.020 for 6×6 mm^2 scan）, number of motion artifacts（AngioVue the fewest： 0.778±1.086 for 3×3 mm^2 scan and 0.333±0.620 for 6×6 mm^2 scan） and acquisition time（AngioPlex the shortest： 8.537±1.921 s for 3×3 mm^2 scan and 8.298±1.741 s for 6×6 mm^2 scan; all P〈0.001）. CONCLUSION： There is poor agreement of measurements among systems. AngioVue provides images with the highest vessel valid visibility and the fewest motion artifacts. AngioPlex achieves the shortest acquisition.

Correlation between mixing enthalpy and structural order in liquid Mg−Si system

The mixing enthalpies and structural order in liquid Mg−Si system were investigated via ab-initio molecular dynamics at 1773 K.By calculating the transferred charges and electron density differences,the dominance of Si−Si interactions in the chemical environments around Si was demonstrated,which determined that the mixing enthalpy reached the minimum on Mg-rich side.In terms of Honeycutt and Anderson(HA)bond pairs based on the partial pair correlation functions,the attraction between Si−Si pairs and Mg atoms was revealed,and the evolution of structural order with Si content was characterized as a process of constituting frame structures by Si−Si pairs that dispersed Mg atoms.Focusing on tetrahedral order of local Si-configurations,a correlation between the mixing enthalpy and structural order was uncovered ultimately,which provided a new perspective combining the energetics with geometry to understand the liquid Mg−Si binary system.

Light Environment Analysis and Design Strategies of Large Commercial Buildings-A Case Study in Harbin

This paper presents a comprehensive survey for the situation of light environment in large commercial building through architecture design information,subjective and objective fieldwork and online survey for three typical commercial building forms( centralized form, covered mall shopping center, lifestyle center).Descriptive method is used for statistical analysis which includes the evaluation of light environmental quality,subjective assessment among daylight and artificial illumination,effect of physical characteristics on subjective assessment of light environment. Based on the results of statistical analysis,the improving strategies for light environment are proposed in terms of making use of daylight,artificial lighting design and improvement of the overall light environmental quality. The design strategies which based on the consumer needs is very important can provide help for further impact prediction on the quality of light environment.

Separation of diffracted waves via SVD filter

Diffracted seismic waves may be used to help identify and track geologically heterogeneous bodies or zones.However,the energy of diffracted waves is weaker than that of reflections.Therefore,the extraction of diffracted waves is the basis for the effective utilization of diffracted waves.Based on the difference in travel times between diffracted and reflected waves,we developed a method for separating the diffracted waves via singular value decomposition filters and presented an effective processing flowchart for diffracted wave separation and imaging.The research results show that the horizontally coherent difference between the reflected and diffracted waves can be further improved using normal move-out(NMO) correction.Then,a band-rank or high-rank approximation is used to suppress the reflected waves with better transverse coherence.Following,separation of reflected and diffracted waves is achieved after the filtered data are transformed into the original data domain by inverse NMO.Synthetic and field examples show that our proposed method has the advantages of fewer constraints,fast processing speed and complete extraction of diffracted waves.And the diffracted wave imaging results can effectively improve the identification accuracy of geological heterogeneous bodies or zones.

Risk factors for adverse outcome in low rectal cancer

AIM: To demonstrate the oncologic outcomes of low rectal cancer and to clarify the risk factors for survival, focusing particularly on the type of surgery performed. METHODS: Data from patients with low rectal carcinomas who underwent surgery, either sphincter-preserving surgery (SPS) or abdominoperineal resection (APR), at The First Aff iliated Hospital of Sun Yat-sen University in China from August 1994 to December 2005 were retrospectively analyzed. RESULTS: Of 331 patients with low rectal cancer, 159 (48.0%) were treated with SPS. A higher incidence of positive resection margins and a higher 5-year cumulative local recurrence rate (14.7% vs 6.8%, P = 0.041) were observed in patients after APR compared to SPS.The five-year overall survival (OS) was 54.6% after APR and 66.8% after SPS (P = 0.018), and the 5-year disease-free survival (DFS) was 52.9% after APR and 65.5% after SPS (P = 0.013). In multivariate analysis, poor OS and DFS were signif icantly related to positive resection margins, pT3-4, and pTNM Ⅲ-Ⅳ but not to the type of surgery. CONCLUSION: Despite a higher rate of positive resection margins after APR, the type of surgery was not identif ied as an independent risk factor for survival.

Ureteral Ewing’s sarcoma in an elderly woman: A case report

BACKGROUND Ewing’s sarcoma(ES)is regarded as a skeletal tumor,with few instances of extraskeletal ES.A primary ES in the ureter is extremely rare.CASE SUMMARY We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter.Pathology of the excised mass indicated ES.The clinical treatment and pathologic characteristics in this case,and a review of the literature describing ES in the urinary system,are presented.CONCLUSION Due to the rarity and malignancy of ES in ureter,early diagnosis and prompt surgical treatment are critical.

Inositol-requiring enzyme 1α is required for gut development in Xenopus lavies embryos

AIM:To investigate the role of inositol-requiring enzyme 1α(IRE1α) in gut development of Xenopus lavies embryos.METHODS:Xenopus embryos were obtained with in vitro fertilization and cultured in 0.1 × MBSH.One and half nanogram of IRE1α,1 ng of IRE1α-GR mRNA,1 ng of IRE1αΔC-GR mRNA,and 50 ng of IRE1α morpholino oligonucleotide(MO) or XBP1(C)MO were injected into four blastomeres at 4-cell stage for scoring the phenotype and marker gene analysis.To rescue the effect of IRE1α MO,1 ng of IRE1α-GR mRNA was coinjected with 50 ng of MO.For the activation of the GR-fusion proteins,dexamethasone was prepared as 5 mmol/L stock solutions in 100% ethanol and applied to the mRNA injected embryos at desired stages in a concentration of 10 μmol/L in 0.1 × MBSH.Embryos were kept in dexamethasone up to stage 41.Whole-mount in situ hybridization was used to determine specific gene expression,such as IRE1α,IRE1β,Xbra and Xsox17α.IRE1α protein expression during Xenopus embryogenesis was detected by Western blotting.RESULTS:In the whole-mount in situ hybridization analysis,xenopus IRE1α and IRE1β showed quite different expression pattern during tadpole stage.The relatively higher expression of IRE1α was observed in the pancreas,and significant transcription of IRE1β was found in the liver.IRE1α protein could be detected at all developmental stages analyzed,from stage 1 to stage 42.Gain-of-function assay showed that IRE1α mRNA injected embryos at tailbud stage were nearly normal and the expression of the pan-mesodermal marker gene Xbra and the endodermal gene Xsox17α at stage 10.5 was not significantly changed in embryos injected with IRE1α mRNA as compared to uninjected control embryos.And at tadpole stage,the embryos injected with IRE1α-GR mRNA did not display overt phenotype,such as gut-coiling defect.Loss-of-function assay demonstrated that the IRE1α MO injected embryos were morphologically normal before the tailbud stages.We did not observe a significant change of mesodermal and endodermal marker gene expression,while after stage 40,about 80% of the MO injected embryos exhibited dramatic gut defects in which the guts did not coil,but other structures outside the gastrointestinal tract were relatively normal.To test if the phenotypes were specifically caused by the knockdown of IRE1α,a rescue experiment was performed by co-injection of IRE1α-GR mRMA with IRE1α MO.The data obtained demonstrated that the gut coiling defect was rescued.The deletion mutant of IRE1α was constructed,consisting of the N-terminal part without the C-terminal kinase and RNase domains named IRE1αΔC,to investigate the functional domain of IRE1α.Injection of IRE1αΔCGR mRNA caused similar morphological alterations with gut malformation by interfering with the function of endogenous xIRE1α.In order to investigate if IRE1α/XBP1 pathway was involved in gut development,50 ng of XBP1 MO was injected and the results showed that knockdown of XBP1 resulted in similar morphological alterations with gut-coiling defect at tadpole stage.CONCLUSION:IRE1α is not required for germ layer formation but for gut development in Xenopus lavies and it may function via XBP1-dependent pathway.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM： To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab（IVR） versus laser therapy in treatment of diabetic macular edema（DME）.METHODS： Pertinent publications were identified through comprehensive searches of Pub Med, EMBASE, Web of Science, Cochrane Library, and Clinical Trials.gov to identify randomized clinical trials（RCTs） comparing IVR＋laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences（WMD） of change from baseline in best corrected visual acuity（BCVA） and central retinal thickness（CRT） at 6, 12, or 24 mo after initial treatment, and the risk ratios（RR） for the proportions of patients with at least 10 letters of improvement or reduction at 12 mo. Data regarding major ocular and nonocular adverse events（AEs） were collected and analyzed. The Review Manager 5.3.5 was used.RESULTS： Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR＋laser significantly improved BCVA compared with laser at 6mo（WMD： 6.57; 95% CI： 4.37-8.77; P〈0.00001）, 12mo（WMD： 5.46; 95% CI： 4.35-6.58; P〈0.00001）, and 24mo（WMD： 3.42; 95% CI： 0.84-5.99; P=0.009） in patients with DME. IVR＋laser was superior to laser in reducing CRT at 12 mo from baseline with statistical significance（WMD：-63.46; 95% CI：-101.19 to-25.73; P=0.001）. The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR＋laser arms compared with laser（RR： 2.13; 95% CI： 1.77-2.57; P〈0.00001 and RR： 0.37; 95% CI： 0.22-0.62; P=0.0002, respectively）. As for AEs, the pooled results showed that a significantly higher proportion ofpatients suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye） in IVR＋laser group compared to laser group（RR： 3.29; 95% CI： 1.53-7.09; P=0.002 and RR： 3.02; 95% CI： 1.24-7.32; P=0.01, respectively）. The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR＋laser and laser alone.CONCLUSION： The results of our analysis show that IVR＋laser has better availability in functional（improving BCVA） and anatomic（reducing CRT） outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR＋laser may get a higher risk of suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye）.

Enhanced absorption process in the thin active region of GaAs based p-i-n structure

The optical absorption is the most important macroscopic process to characterize the microscopic optical transition in the semiconductor materials. Recently, great enhancement has been observed in the absorption of the active region within a p–n junction. In this paper, Ga As based p–i–n samples with the active region varied from 100 nm to 3 μm were fabricated and it was observed that the external quantum efficiencies are higher than the typical results, indicating a new mechanism beyond the established theories. We proposed a theoretical model about the abnormal optical absorption process in the active region within a strong electric field, which might provide new theories for the design of the solar cells,photodetectors, and other photoelectric devices.

Quantitative analysis of retinal intermediate and deep capillary plexus in patients with retinal deep vascular complex ischemia

AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was calculated.RESULTS: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.

A New Stopping Criterion for Eckstein and Bertsekas’s Generalized Alternating Direction Method of Multipliers

In this paper,we propose a new stopping criterion for Eckstein and Bertsekas’s generalized alternating direction method of multipliers.The stopping criterion is easy to verify,and the computational cost is much less than the classical stopping criterion in the highly influential paper by Boyd et al.(Found Trends Mach Learn 3(1):1–122,2011).

Controllable Photoelectric Properties of Carbon Dots and Their Application in Organic Solar Cells

Organic solar cells are a current research hotspot in the energy field because of their advantages of lightness,translucency,roll to roll printing and building integration.With the rapid development of small molecule acceptor materials with high-performance,the efficiency of organic solar cells has been greatly improved.Further improving the device efficiency and stability and reducing the cost of active layer materials will contribute to the industrial development of organic solar cells.As a novel type of carbon nanomaterials,carbon dots gradually show great application potential in the field of organic solar cells due to their advantages of low preparation cost,non-toxicity and excellent photoelectric performance.Firstly,the synthesis and classification of carbon dots are briefly introduced.Secondly,the photoelectric properties of carbon dots and their adjusting,including adjustable surface energy level structure,good film-forming performance and up/down conversion characteristics are summarized.Thirdly,based on these intrinsic properties,the feasibility and advantages of carbon dots used in organic solar cells are discussed.Fourthly,the application progress of carbon dots in the active layer,hole transport layer,electron transport layer,interface modification layer and down-conversion materials of organic solar cells is also reviewed.Finally,the application progress of carbon dots in organic solar cells is prospected.Several further research directions,including in-depth exploration of the controllable preparation of carbon dots and their application in the fields of interface layer and up/down conversion for improving efficiency and stability of device are pointed out.

A strategy for rapid discovery of traceable chemical markers in herbal products using MZmine 2 data processing toolbox:A case of Jing Liqueur

Objective:The quality evaluation of herbal products remains a big challenge.Traceable markers are the core concept of the authentication of herbal products.However,the discovery of traceable markers is labor-intensive and time-consuming.The aim of this study is to develop a convenient approach to rapidly screen the traceable markers for herbal product authentication.Methods:Commercial Jing Liqueur and its 22 species of herbal ingredients were analyzed using HPLCQTOF-MS and GC–MS to characterize nonvolatile and volatile chemicals.The acquired data were imported into MZmine 2 software for mass detection,chromatogram building,deconvolution and alignment.The aligned data were exported into a csv file and then traceable markers were selected using the built-in filter function in Excel.Finally,the traceable markers were identified by searching against online databases or publications,some of which were confirmed by reference standards.Results:A total of 288 chemical features transferred from herbal materials to Jing Liqueur product were rapidly screened out.Among them,52 markers detected by HPLC-QTOF-MS were annotated,while nine volatile markers detected by GC–MS were annotated.Moreover,30 of these markers were confirmed by comparing with reference standards.A chemical fingerprint consisting of traceable markers was finally generated to ensure the authentication and quality consistency of Jing Liqueur.Conclusion:A strategy for rapid discovery of traceable markers in herbal products using MZmine 2 software was developed.

A comparison study between 2D and 3D slope stability analyses considering spatial soil variability

In engineering practice,the stability of a slope is often analyzed as a 2D problem assuming a plane-strain condition,which may lead to significant errors.In this paper,a comprehensive study is carried out to compare the results of 2D and 3D slope stability analyses,using the strength reduction method for deterministic analysis and the random field approach for probabilistic analysis,respectively.The results of this comparison study confirm that in the deterministic stability evaluation,the 2D analysis tends to obtain a smaller factor of safety than does its 3D counterpart.In the probabilistic evaluation that considers the spatial variability of soil properties,the 2D analysis tends to yield a larger probability of failure than its 3D counterpart.A significant feature of the 3D probabilistic slope stability analysis is the presence of multiple local failures distributed along the slope longitudinal direction.This paper provides insights regarding the degree of errors in modeling a 3D slope as a 2D problem,which can be regarded as a complement to the previous 3D slope stability analyses.