Prognostic Value of Vimentin Is Associated With Immunosuppression in Metastatic Renal Cell Carcinoma.

Introduction: Vimentin, a classical marker of epithelial-mesenchymal transition, reflects the invasiveness of cancer cells. Its role in the genesis and progression of tumor has been reported in various cancers, including renal cell carcinoma. However, the impact of vimentin on tumor microenvironment, particularly its implication with tumor-infiltrating immune cells, is unknown. Methods: We conducted this study in 231 patients with metastatic renal cell carcinoma (mRCC) to determine the potential relationship between vimentin and immune status. Using immunohistochemical staining, expression of vimentin, CD8, FOXP3, programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) were evaluated in resected tumor tissue. Kaplan-Meier analysis and Cox regression models were used for survival analysis. Chi-square test, Fisher exact test, and Mann-Whitney U-test were used for comparison between vimentin high and low groups. Results: High expression of vimentin, stroma PD-L1, and PD-1 indicated poor overall survival, whereas low regulatory T cell or high CD8+ T cell infiltration indicated long overall survival. Stroma PD-L1 (P = 0.030), vimentin (P = 0.026) expression, and CD8+ T cell infiltration (P < 0.001) were independent prognostic factors in mRCC. High vimentin expression was accompanied by high PD-1, PD-L1 expression, and increased regulatory T cell infiltration (all P < 0.001), indicating immunosuppression in the tumor microenvironment. Conclusions: We revealed that vimentin expression was associated with immunosuppression in mRCC, and the immune-suppressive status might be possibly posed by PD-1/PD-L1. Patients with high vimentin expression may acquire potential benefit from the recently approved PD-1/PD-L1 inhibitors. However, further clinical trials are needed to validate our findings.

Immunoscore System for Predicting Clinical Outcome of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors.

We conducted this study to determine whether immunoscore system (IS) predicts survival in patients with metastatic renal cell carcinoma (mRCC). A total of 218 mRCC patients treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were recruited during 2007-2017, retrospectively. CD8, CD4, Treg, PD-1 and PD-L1 expression were evaluated by immunohistochemical staining of paraffin embedded slide. Kaplan-Meier method and COX regression model were used in survival analyses. Multivariate analyses demonstrated that expressions of CD8, Treg, PD-1 and stromal PD-L1 (sPD-L1) expressions were independent predictive factors for OS, thus IS was established containing these four immunological factors. Subsequent analysis revealed that performance of IS provided good differentiation of OS and PFS. Besides, multivariate analysis identified IS as an independent prognostic factor for OS (p<0.001) and PFS (p=0.002). IS, compared with International mRCC Database Consortium (IMDC) risk model, and provided better prediction ability for OS. Results suggested that IS was a powerful prognostic factor for OS and PFS in patients with mRCC treated with tyrosine kinase inhibitors. And IS can be used as essential supplement to IMDC for outcome prediction in mRCC patients.

The relationship between preoperative psychological evaluation and compensatory sweating.

BACKGROUND: This study analyzes the relationship between preoperative psychological states of primary palmar hyperhidrosis patients and postoperative compensatory sweating. METHODS: We evaluated the psychological states of patients with primary palmar hyperhidrosis who received sympathectomy in our hospital from 2016 to 2017. The relationship between preoperative psychological states and postoperative compensatory sweating were assessed using Spearman's rank-order correlation. RESULTS: Fifty-five patients who received R4 + R3 bypass transection accepted the preoperative questionnaire survey; 35 were males and 20 were females. The average age was 24.0 ± 6.3 years (range, 14-44 years). Depression symptoms were present in 21.9% (12/55) of the patients; the incidence of anxiety was almost similar, at 23.7% (13/55). Compensatory sweating occurred in 67.3% (37/55) of the patients; of these, 56.4% (31/55) was mild and 10.9% (6/55) was moderate. None of the patients had severe compensatory sweating. There was no significant relationship between the scores of SDS, SAS, and the incidence of postoperative compensatory sweating (P>0.05). However, the psychoticism scale displayed a strong impact on the degree of compensatory sweating (P<0.05). The higher the degree of psychoticism scale, the more serious the degree of compensatory sweating. CONCLUSIONS: The results of this study showed that patients with primary palmar hyperhidrosis are more likely to have mild or moderate mental disorders, and that postoperative compensatory sweating may impact the satisfaction of surgery. In addition, the personality characteristics of patients are related to compensatory sweating.

Amplified detection of genome-containing biological targets using terminal deoxynucleotidyl transferase-assisted rolling circle amplification.

We proposed a terminal deoxynucleotidyl transferase (TdT)-assisted rolling circle amplification (RCA) strategy for the amplified detection of genome-containing biological targets. The synergetic signal amplification of DNase I-mediated genomic DNA fragmentation and subsequent RCA allow the sensing platform to have extraordinarily high sensitivity.

Stable, polyvalent aptamer-conjugated near-infrared fluorescent nanocomposite for high-performance cancer cell-targeted imaging and therapy.

Early diagnosis and targeted therapy are two important ways to improve cancer treatment survival. In this work, via a simple DNA hybridization reaction, DNA-templated fluorescent silver nanoclusters (AgNCs) were successfully assembled around a DNA-modified gold nanoparticle (AuNP) to construct a novel nanocomposite with the functions of cancer cell-specific imaging and targeted therapy. The as-prepared AuNP@(AS1411-AgNCs)n nanocomposite shows strong near-infrared fluorescence emission and improved biostability, and carries a high density of AS1411-the first anticancer aptamer targeting nucleolin protein, which is over-expressed not only on the surface but also in the cytoplasm of cancer cells. The synergy of multivalent AS1411-nucleolin binding promotes accumulation of the nanocomposite towards cancer cells and subsequent internalization in them. This results in highly specific cancer cell-targeted imaging and selective killing in a low AuNP@(AS1411-AgNCs)n concentration range. The prepared nanocomposite also shows great potential as a carrier of doxorubicin to further promote the selective killing of cancer cells.

Biostable L-DNA-Templated Aptamer-Silver Nanoclusters for Cell-Type-Specific Imaging at Physiological Temperature.

The high susceptibility of the natural D-conformation of DNA (D-DNA) to nucleases greatly limits the application of DNA-templated silver nanoclusters (Ag NCs) in biological matrixes. Here we demonstrate that the L-conformation of DNA (L-DNA), the enantiomer of D-DNA, can also be used for the preparation of aptamer-Ag NCs. The extraordinary resistance of L-DNA to nuclease digestion confers much higher biostability to these NCs than those templated by D-DNA, thus making cell-type-specific imaging possible at physiological temperatures, using at least 100-times lower Ag NC concentration than reported D-DNA-templated ones. The L-DNA-templated metal NC probes with enhanced biostability might promote the applications of metal nanocluster probes in complex biological systems.

Hsa-mir-182 downregulates RASA1 and suppresses lung squamous cell carcinoma cell proliferation.

BACKGROUND: This work was undertaken to identify the differences in expression of miRNAs, which would predict early-stage non-small cell lung cancer prognosis and recurrence. The results may be helpful to demonstrate one mechanism of lung squamous cancer proliferation. METHODS: Lung squamous cell carcinoma specimens were collected at the time of surgery. Microarray of expression of specific miRNAs in lung squamous cell cancer tissue, were assessed by qRT-PCR. RESULTS: We found that the hsa-mir-182 family are highly expressed in lung squamous cell carcinoma. Paradoxically, our study reveals mir-182 suppresses cell proliferation in vivo. RASA1 is related to cell apoptosis. We further show that mir-182 downregulates RASA1. CONCLUSIONS: We provide first time evidence through tissue microarray and quantitative PCR validation of mir-182 in the expression of lung squamous cell carcinoma. Our data provide a possible mechanism for lung cancer cell proliferation in lung squamous cell cancer and may be helpful in discovering a new strategy to reveal lung squamous cell carcinoma progress.

[Expression of PAR-1 in human lung carcinoma and its relationship with tumor metastatic potential].

OBJECTIVE: To explore the correlation between expression of PAR-1 and metastasis of human lung carcinoma. METHODS: Expression levels of PAR-1 were examined in surgically resected lung carcinoma specimens and corresponding lymph nodes by RT-PCR and immunohistochemistry, combined with morphometric methodology and clinicopathologic profiles. RESULTS: Strong PAR-1 staining was detected in the periphery of carcinoma nests, adenocarcinomatous emboli, foci of atypical adenomatous hyperplasia adjacent to the adenocarcinoma and atypical proliferation of duct epithelium of bronchial mucous glands. The expression rates of PAR-1 were 73.8% (59/80) and 63.9% (23/36) by immunohistochemistry and RT-PCR respectively. The percentage of PAR-1 protein expression cells was significantly higher in tumors with metastasis (85.7%, 48/56) than those without (45.8%, 11/24). Morphometric study demonstrated that there were significant differences of PAR-1 protein expression levels between tumors with metastatic and those without, primary and metastatic carcinomas, primary carcinomas and benign lung tissues adjacent to the carcinoma. No significant correlation was found between PAR-1 expression level and tumor size, histological types and tumor grades. The positive rate of PAR-1 mRNA expression in the metastatic group was significantly higher than that of the non-metastatic group (78.3%, 18/23 v.s. 38.5%, 5/13). CONCLUSION: PAR-1 expression may play an important role in determining the malignant phenotypes of lung cancers and significantly contribute to their initiation, progression and metastasis.

Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells.

This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.

catena-poly[[[diaqua[trans-3-(4-pyridyl)acrylato]samarium(III)]-di-mu-trans-3-(4-pyridyl)acrylato] dihydrate].

In the title compound, {[Sm(4-pya)(3)(H(2)O)(2)].2H(2)O}(n) [4-pya is trans-3-(4-pyridyl)acrylate, C(8)H(6)NO(2)], each Sm(III) atom is ten-coordinated and has a bicapped square-antiprismatic coordination geometry. There is a crystallographic center of symmetry at the mid-point of the Sm...Sm line within each [Sm(4-pya)(3)(H(2)O)(2)](2) dimer. Each dimer is interconnected by two pairs of bridging 4-pya ligands to form a one-dimensional chain. Neighboring chains are connected via hydrogen bonds to form a three-dimensional network.

[Experimental study on human reaction of determination and performance in virtual environment].

OBJECTIVE: To study factuality of ergonomic experimental data from subjects performing virtual environment wearing head mounted display (HMD) and data gloves, so as to improve the reliability of the application of virtual reality in manned spaceflight (e.g. human-machine interface design scheme ergonomic evaluation, and virtual training). METHOD: Experiment in a virtual module is designed and implemented on the virtual reality ergonomic experimental system. First, pre-experiments are done to determine the different levels of objects to be operated and the height of a virtual table which is in the virtual module. On the basis of the pre-experiments, the formal experiments are completed. In addition, a virtual reality questionnaire (VRQ) is developed and employed in order to assess subjective impressions of the virtual environment. RESULT: Normal distribution of performing time is shown when a virtual sphere is put into a drawer of standard cabinet of virtual module on a front table by subjects wearing HMD, its mean value being 36.72 s and variance being 13.798 s. By VRQ analysis, about 70.2% of the subjects thought that HMD has a good stereo quality, they can be immersed in the virtual module. CONCLUSION: When virtual reality is applied in ergonomic evaluation or virtual training, the HMD and data glove of the system would satisfy the requirements of human-computer interaction, so that human performance can be analogized and corresponding truth of experimental result can be achieved.

[Effects of field viewing angles on object judgement [correction of jubgerent] in virtual environment].

OBJECT: To investigate the effect of viewing angle on human judgement reliability for objects in virtual environment. METHOD: Firstly, pre-tests were done with the PC virtual reality ergonomic system to determine difference among observed object and values of viewing angle. Then, one factor, 4-levels full random experiments were done with 45 health human subjects (male and female nearly 1:1). RESULT: It was shown that the reliability of human judgement was significantly influenced by the setting of the viewing angle of virtual environment, and the object judgement including size and angle judgement was the best when the viewing angle of virtual environment was 60 degrees. CONCLUSION: When virtual reality was used in ergonomic design, operation training and other related research, the effect of field viewing angle should be taken into consideration, and 60 degrees is recommended to be optimal for human judgment task.