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IntroductionImmune checkpoint inhibitors (ICIs), including toripalimab and pembrolizumab, have not been testified in treatment of cancer of unknown primary, which has a very poor prognosis. Combined with anti-angiogenic therapies, ICIs are hypothesized to be effective in prolonging overall survival. The study aims to give evidence on the treatment effects of sunitinib combined with ICIs, find pathological biomarkers associated with changes in volumetric PET/CT parameters, and interrogate inner associations among these markers associated with response on PET/CT.MethodsThe study recruited patients receiving combined treatment (ICIs + sunitinib) and compare the effects with separate treatment and with age-matched negative controls, analyzed in propensity score-matched (PSM) pairs. Markers associated with survival were identified and their inner associations were tested with structural equation modeling.ResultsA total of 292 patients were enlisted in the final analysis with 53 patients receiving combined treatment. Survival analysis demonstrated significantly prolonged survival in either combined or separate treatment, with the combined arm showing better response when PSM-paired by pre-treatment whole-body PET/CT parameters. Angiogenic marker KDR and VEGF mediates the PD-1 blockade impact on volumetric value changes, in positive and negative manners, respectively.ConclusionAnti-angiogenic agents sunitinib may potentiate PD-1 blockade by diminishing angiogenesis or its downstream effects. The combined separate treatment increased survival of CUP patients and the responses could be evaluated by volumetric PET/CT parameters.

BackgroundAnaplastic and poorly differentiated thyroid carcinoma (ATC/PDTC) have poor survival outcomes. Mono-therapy with either immuno-therapy or tyrosine kinase blockers (TKI) is sparsely reported and seems not to significantly affect prognosis or survival. We sought to testify whether combined therapies have a better outcome in real-world settings. Pathological plus PET/CT volumetric biomarkers were analyzed to find crosstalk associated with response.MethodsPatients receiving PD-1 blockers alone or combined with anlotinib were recruited to undergo sequential PET/CT scanning. Propensity score-matched analysis was carried out for comparison of treatment outcomes. Structure equation modeling was carried out to investigate the crosstalk among sensitive biomarkers. A nomogram was developed and validated using the patients in the same centers.ResultsA total of 69 patients received either combined or mono-therapy with a clinical benefit rate of 88.41% (61 / 69) and tolerable adverse events, with a mean survival time of 14.64 months. The mean survival time of the combined therapy group was 15.67 months. The mean improvement of total lesion glycolysis (TLG) for the combined group was 120.07 (29.42% improved from baseline). Angiogenic marker VEGFR, FGFR, and VEGF mediate the PD-1 blockade impact on TLG improvement.ConclusionAnti-angiogenic agents anlotinib could potentiate PD-1 blockade by diminishing angiogenesis or its downstream effects. The combined treatment increased survival and responses could be better evaluated by volumetric PET/CT parameters. Pathological biomarker expression levels were associated with TLG improvement in combined treatment.

BackgroundPatients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of progression cell death-1 blockers (PD-1B) on immune or vaccine-related outcomes, and what risk factors that contribute to the serological status remains to be elucidated. The study aims to find the impact of PD-1B on vaccination outcome and investigate other potential risk factors associated with the risk of seroconversion failure.MethodsPatients with active cancer treatment were retrospectively enrolled to investigate the interaction effects between PD-1B and vaccination. Through propensity score matching of demographic and clinical features, the seroconversion rates and immune/vaccination-related adverse events (irAE and vrAE) were compared in a head-to-head manner. Then, a nomogram predicting the failure risk was developed with variables significant in multivariate regression analysis and validated in an independent cohort.ResultsPatients (n=454) receiving either PD-1B or COVID-19 vaccination, or both, were matched into three cohorts (vac+/PD-1B+, vac+/PD-1B-, and vac-/PD-1B+, respectively), with a non-concer control group of 206 participants. 68.1% (94/138), 71.3% (117/164), and 80.5% (166/206) were seropositive in vac+/PD-1B+cohort, vac+/PD-1B- cohort, and non-cancer control group, respectively. None of irAE or vrAE was observed to be escalated in PD-1B treatment except for low-grade rash.The vaccinated patients with cancer had a significantly lower rate of seroconversion rates than healthy control. A nomogram was thus built that encompassed age, pathology, and chemotherapy status to predict the seroconversion failure risk, which was validated in an independent cancer cohort of 196 patients.ConclusionAlthough patients with cancer had a generally decreased rate of seroconversion as compared with the healthy population, the COVID-19 vaccine was generally well tolerated, and seroconversion was not affected in patients receiving PD-1B. A nomogram predicting failure risk was developed, including age, chemotherapy status, pathology types, and rheumatic comorbidity.

Background: Preoperative estimation of microvascular invasion is of great significance for the clinical decision making in hepatocellular carcinoma. Neutrophil-lymphocyte ratio (NLR) has been reported to be correlated with the poor prognosis of hepatocellular carcinoma. However, the conclusions are conflicting on whether high preoperative NLR level is associated with the presence of microvascular invasion. Aim: To evaluate the association between preoperative NLR level and the risk of microvascular invasion in hepatocellular carcinoma. Methods: Relevant studies were identified by searching PubMed and Embase through February 2019. Fixed or random models were applied to analyze the data based on the heterogeneity. Subgroup, sensitivity, and publication bias analyses were performed. Review Manager 5.3 and STATA software were used for the meta-analysis. Results: A total of 15 studies were eventually included in this meta-analysis. Pooled data based on retrospective cohort studies showed there are more hepatocellular carcinoma patients with vascular invasion (OR 1.74; 95% Cl 1.42, 2.12; P < 0.001) and microvascular invasion (OR 1.62 95% Cl 1.39, 1.89; P < 0.001) in the high NLR group than in the low NLR group. Of case-control studies, a higher preoperative NLR level was found in the microvascular invasion positive group than in the microvascular invasion negative group (OR 0.62; 95% Cl 0.35, 0.90; P < 0.001). The subgroup, sensitivity, and publication bias analyses did not change the results. Conclusion: A higher preoperative NLR level is positively correlated with the risk of microvascular invasion in hepatocellular carcinoma.

INTRODUCTION: The ongoing worldwide pandemic of coronavirus disease 2019 (COVID­19) has posed a huge threat to global public health. However, the issue as to whether routine blood tests could be used to monitor and predict the severity and prognosis of COVID­19 has not been comprehensively investigated so far. OBJECTIVES: This study aimed to provide an overview of the association of markers in the routine blood test with the severity of COVID­19. METHODS: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies reporting data on markers in the routine blood test and the severity of COVID­19, published until March 20, 2020. The STATA software was used for meta­analysis. RESULTS: A total of 15 studies with 3090 patients with COVID­19 were included in this analysis. Patients in the nonsevere group, compared with those in the severe group, had lower counts of white blood cells (weighted mean difference [WMD], -0.85 [×109/l]; 95% CI, -1.54 to -0.16; P = 0.02) and neutrophils (WMD, -1.57 [×109/l]; 95% CI, -2.6 to -0.54; P = 0.003), greater counts of lymphocytes (WMD, 0.29 [×109/l]; 95% CI, 0.22-0.36; P

The coercivity of sintered Nd-Fe-Cu-B magnets is markedly enhanced from 12.57 to 21.70 kOe while the remanence decreases from 13.80 to 13.49 kGs by grain boundary diffusion of TbF3 powder for 2 h. Microstructure analysis suggests that, during the diffusion process, F diffuses into the magnets easily and forms a new F-rich phase. The enrichment of F in grain boundary near the surface leads to the Cu movement into the interior and the Cu reduction in the surface of magnets. Diffusion of Tb leads to an increase of local total rare earth elements content. Under the combined effect of Cu reduction and increase of local total rare earth elements content, grain growth area is formed and further diffusion is suppressed. That excessive Tb diffuses into matrix phase leads to a decrease in remanence. When the grain growth area is removed, the deterioration of remanence recovers to 13.80 kGs without any reduction of coercivity.

Supplemental Digital Content is available in the text, Background: Small nucleolar RNA host gene 20 (SNHG20) is a newly identified long non-coding RNA (lncRNA). Accumulative evidence suggest that SNHG20 is highly related to tumorigenesis. However, whether the levels of SNHG20 can be used for prognosis of patients with different cancer types was unclear. The present study aims to explore the role of SNHG20 in tumor prognosis and its clinical significance. Methods: Related articles published before March 14, 2019 were searched in PubMed, Excerpta Medica Database (EMBASE), ISI Web of Science, and China National Knowledge Infrastructure (CNKI). Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were obtained using Stata 11.0 software and used to for determination of the link between the levels of SNHG20 and overall survival (OS). Fixed or random model was chosen depending on the heterogeneity of the studies. A quality assessment of the included studies was performed according to the Newcastle-Ottawa scale. This study was approved by the Medical Ethics Committee of Xiangya Hospital of Central South University. Results: After a strict filtering process, a total of 1149 patients from 15 studies were enrolled in this study. Pooled data showed that elevated level of SNHG20 was correlated not only with poor overall survival (HR = 2.49, 95% confidence interval (CI): 2.05–2.98), but also with tumor-node-metastasis stage (TNM) (odds ratio (OR) = 3.32, 95% CI: 2.27–4.86), high histological grade (OR = 2.11, 95% CI: 1.55–2.87), tumor size (OR = 2.92, 95% CI: 2.17–3.91), and lymph node metastasis (OR = 4.48, 95% CI: 2.90–6.92). Of note, there is no significant heterogeneity difference among the studies. Conclusion: Up-regulated SNHG20 predicts unfavorable prognosis for multiple kinds of cancers although further studies are in need to verify its clinical applications.

The La doped ceramics PLZT-0.03/1-x/x (0.43 ≤ x ≤ 0.49) around morphotropic phase boundary (MPB) region were prepared by solid-state reaction. The ceramics exhibited diffused phase transition behavior, while MPB region showed the least degree of diffusion. It has been shown that distinct difference exists between poled and unpoled samples. All the samples exhibited thermal hysteresis behavior characteristic of the first order phase transition. The ferroelectric properties of the samples were also discussed.

Supplemental material, supplementary_materials for Preoperative neutrophil-lymphocyte ratio predicts the risk of microvascular invasion in hepatocellular carcinoma: A meta-analysis by Furong Zeng, Bin Chen, Jiling Zeng, Zhiming Wang, Liang Xiao and Guangtong Deng in The International Journal of Biological Markers

Ribonucleotide reductase (RR) is the rate-limiting enzyme in DNA synthesis, catalyzing the reduction of ribonucleotides to deoxyribonucleotides. During each enzymatic turnover, reduction of the active site disulfide in the catalytic large subunit is performed by a pair of shuttle cysteine residues in its C-terminal tail. Thioredoxin (Trx) and glutaredoxin (Grx) are ubiquitous redox proteins, catalyzing thiol-disulfide exchange reactions. Here, immunohistochemical examination of clinical colorectal cancer (CRC) specimens revealed that human thioredoxin1 (hTrx1), but not human glutaredoxin1 (hGrx1), was up-regulated along with human RR large subunit (RRM1) in cancer tissues, and the expression levels of both proteins were correlated with cancer malignancy stage. Ectopically expressed hTrx1 significantly increased RR activity, DNA synthesis, and cell proliferation and migration. Importantly, inhibition of both hTrx1 and RRM1 produced a synergistic anticancer effect in CRC cells and xenograft mice. Furthermore, hTrx1 rather than hGrx1 was the efficient reductase for RRM1 regeneration. We also observed a direct protein-protein interaction between RRM1 and hTrx1 in CRC cells. Interestingly, besides the known two conserved cysteines, a third cysteine (Cys779) in the RRM1 C terminus was essential for RRM1 regeneration and binding to hTrx1, whereas both Cys32 and Cys35 in hTrx1 played a counterpart role. Our findings suggest that the up-regulated RRM1 and hTrx1 in CRC directly interact with each other and promote RR activity, resulting in enhanced DNA synthesis and cancer malignancy. We propose that the RRM1-hTrx1 interaction might be a novel potential therapeutic target for cancer treatment.

The nanoscale domain structure and variation of local elasticity in lead-free piezoelectric ceramics were investigated using home-made piezoresponse force microscope (PFM) and low-frequency scanning probe acoustic microscope (SPAM) based on a commercial atomic force microscope. The static domain structure and domain dynamics during polarization reversal were studied by PFM, while SPAM investigations showed the elastic and subsurface ferroelectrics structures. PFM and SPAM provided powerful tools for measurements of the local electromechanical and elastic properties of lead-free piezoelectric ceramics.

// Xijuan Wang 1, * , Peng An 1, * , Jiling Zeng 1 , Xiaoyan Liu 1 , Bo Wang 1 , Xuexian Fang 1 , Fudi Wang 1, 2 , Guoping Ren 1 , Junxia Min 1 1 The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310058, China 2 Department of Nutrition, Precision Nutrition Innovation Center, School of Public Health, Zhengzhou University, Zhengzhou 450001, China * These authors contributed equally to this work Correspondence to: Junxia Min, email: junxiamin@zju.edu.cn Guoping Ren, email: gpren2002@163.com Fudi Wang, email: fudiwang.lab@gmail.com , fwang@zju.edu.cn Keywords: prostate cancer, ferritin, PSA Received: September 20, 2016 Accepted: January 24, 2017 Published: February 01, 2017 ABSTRACT Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13−1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores ( p 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher ( p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls ( n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity ( r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Ceramic samples of 0.36BiScO3 · 0.64PbTiO3 morphotropic phase boundary solid solutions modified with low-melting additives (bismuth, nickel, and manganese oxides and lithium fluoride; < 5 wt %) have been prepared by solid-state reactions, and the phase formation, microstructure, and dielectric properties of the ceramics have been investigated. The additives were shown to lower the formation temperature of the solid solutions and raise the density of the ceramics. Varying the heat treatment conditions, we obtained single-phase samples, both large-grained, ranging in grain size from a few to tens of microns, and fine-grained, with a submicron-scale microstructure. The ceramics were shown to form through liquid-phase sintering. The additives influenced the dielectric properties, electrical conductivity, Curie temperature, and dielectric relaxation of the ceramics.

Ferroelectrics with high TC > 600 K attract much attention due to prospects of their applications at high temperatures. In this work, influence of partial substitutions on the crystal structure and dielectric properties of lead-free bismuth oxides Ca(Bi1-x Nd x )4Ti4O15 (x = 0, 0.1) have been studied. Ceramic solid solutions have been prepared by the solid state reactions. Optimal temperatures of synthesis and sintering of the samples were determined. Phase composition, structure and microstructure of the samples were studied using the X-ray diffraction and scanning electron microscopy methods, respectively. Phase transitions and ferroelectric properties were studied by the dielectric spectroscopy. Positive effect of the Mn2O3 and Bi2O3 additives was proved. They favor to improving density of ceramics, inhibiting grain growth and to decreasing dielectric loss.

Layer-structured bismuth calcium titanate CaBi4Ti4O15 is regarded as one of the promising candidates among lead-free oxides for high temperature piezoelectric applications due to its high Curie temperature TC > 1000 K. Influence of partial cation substitutions on phase formation, microstructure and dielectric properties of CaBi4Ti3.6 B 0.4O15 (B – Ti, Cr, Ta) ceramics was studied. Ceramic solid solutions were synthesized by the conventional ceramic method and studied using the X-ray diffraction, scanning electron microscopy and dielectric spectroscopy over a wide temperature and frequency ranges. It was proved that Mn2O3 and Bi2O3 additives enhanced the phase formation process, improved density of ceramics and their dielectric properties.

The ferroelectric and piezoelectric properties of ceramic solid solutions having a composition of (1−x)(Bi0.9Nd0.1)(Sc0.9 B 0.1)O3 − x PbTiO3 (x = 0.60–0.66; B = Lu, Yb, Er, Y) and obtained by solid state reaction were studied. An increase in the Curie temperature was found upon an increase in the concentration of lead titanate, while a drop occured upon the doping of the A and B sublattices. It was shown that at high temperatures, MnO2 and Bi2O3 additives lead to a reduction in the total conductivity and a dielectric loss of less than one order of magnitude. In modified ceramics, an increase in the d 33 and k t piezoelectric coefficients was observed as well. The effects of dielectric relaxation that are determined by the composition of the ceramics were revealed.

Ceramic solid solutions (1-x)(Bi0.9Nd0.1)(Sc0.9B0.1)O3 - xPbTiO3 (x = 0.60–0.66; B - Lu, Yb, Er, Y) based on the compositions close to the morphotropic boundary, have been prepared. To improve the phase content and the resistance of ceramics, Bi2O3 and MnO2 additives were used. Phase composition, structure, microstructure, phase transitions, ferroelectric and piezoelectric properties have been studied. The 1st order ferroelectric phase transitions are marked by peaks near 700–750 K in dielectric permittivity and dielectric loss temperature dependences. Effect of dielectric relaxation was observed, its relation to composition of ceramics determined. The Curie temperature TC increase was observed with increasing the PbTiO3 constituent, while the TC decrease is typical of the A- or B-cations doped compositions. Introduction of MnO2 and/or Bi2O3 additives lead to the decrease of total conductivity and dielectric losses to more than one order at elevated temperatures. Enhanced d33 and kt values were measured i...

The CeO2-doped bismuth-layered structural (Ca,Sr)Bi4Ti4O15 ceramics, one of the most attractive materials with high Curie temperature were prepared by the solid state reaction method. The crystal structure of the ceramics was determined by X-ray diffraction. The doping of CeO2 increased the lattice parameters a, b, c and crystal volume, though the single orthorhombic structure phase was still remained. The effect on the content of the Ce ions to the dielectric properties of the ceramics were also investigated, such as the hysteresis loops, dielectric constants, Curie temperature (TC) and so on. The piezoelectric failure at the temperature much lower than the Curie temperature was found. The mechanism of the Ce ions doping and failure were also analyzed.

The magnetic domain structure in oriented Tb 0.3 Dy 0.7 Fe 1.92 (Terfenol-D) is investigated by scanning electron acoustic microscopy (SEAM) in a wide frequency range from 75 to 530 kHz. Both secondary electron image and electron acoustic image can be obtained in situ simultaneously. By changing the modulation frequencies, the SEAM can be used as an effective nondestructive method to observe not only the surface topography and domain structure but also the subsurface domain structure and defects. The magnetic domain structure is verified by magnetic force microscopy (MFM). Furthermore, magnetic domains can be observed in both linear and nonlinear imaging modes by SEAM. The contributions to the image contrast are related to the signal generation through the piezomagnetic coupling mechanism, magnetostrictive coupling mechanism, and thermal-wave coupling mechanism.

Ferromagnetic phase of Mn-Al exhibits great potential in the rare-earth free permanent magnetic materials due to its high magnetocrystalline anisotropy, high magnetization, high Curie temperature and low cost. In this work, the strip casting technique was applied to prepare MnAl magnetic phase. X-ray diffraction and energy dispersive X-ray analyses indicate that the as-prepared Mn54Al46 strip sample consists of pure τ-MnAl magnetic phase. It is found that the composition of Mn54Al46 is suitable to prepare τ-MnAl phase during the strip casting process. The Mn54Al46 strip sample synthesized through the strip casting exhibits a fairly high magnetization of 114 emu/g under a field of 5 T, while the coercivity of iHc = 2.8 kOe, magnetization of M5T = 63.9 emu/g at room temperature can be obtained for Mn54Al46 powder sample. This preparation method can produce a large amount of τ-phase MnAl alloy and promote mass industrialized production.