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Abstract Background CD2‐associated protein (CD2AP) is a podocyte‐associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. Methods Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT‐qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan–Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP‐related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor‐infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. Results We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. Conclusions Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.

BackgroundMetabolic risk factors in primary biliary cholangitis (PBC) have not been well described in China. Additionally, it is unclear whether these factors have an impact on the prognosis of PBC patients. Therefore, this study aimed to investigate the prevalence of main metabolic risk factors in PBC, and to evaluate their prognostic values for liver-related outcomes.MethodsA cohort of 789 PBC patients was retrospectively studied between July 2008 and September 2019 by investigating the main metabolic risk factors and analyzing liver-related outcomes.ResultsAt presentation, 271 (34.3%) patients had concomitant hyperlipidemia, 126 (16.0%) had hypertension, 94 (11.9%) had type 2 diabetes mellitus (T2DM), and 17 (2.2%) had nonalcoholic fatty liver disease (NAFLD). Hyperlipidemia was found to be associated with the lower risk of liver-related death [P

The dedifferentiation of the gastrointestinal stromal tumors (GISTs) has been reported in a small number of cases, usually under the pressure of the tyrosine kinase inhibitor (TKI) treatment. Herein, we described a de novo dedifferentiated GIST with the SDH deficiency in a 32-year-old Chinese woman. The tumor was located on the lesser curvature of the gastric antrum, measuring 4.1x9.1 cm2. Microscopically, the tumor was composed of 2 distinct morphological populations, mild epithelioid cells arranged in the multinodular growth pattern and hyperchromatic spindle cells arranged in the fascicular or sheet-like architecture. The two zones showed different immunophenotypes. The former proved to be an epithelioid GIST with the positive expression for C-KIT, DOG-1, and CD34, and the latter expressed the CKpan and P53, but negative for the C-KIT, DOG-1, and CD34. However, the SDHB staining was negative in both areas. Genetically, the next-generation sequencing (NGS) analysis showed the SDHC mutation (p.S48*) in both components and the MDM2 amplification was only in the spindle cell area. The lesion was diagnosed as the SDH-deficient GIST with the epithelial cell dedifferentiation. We proposed that the P53 associated gene alteration or other alternative escape mechanisms for the KIT-independent signaling pathways might play a role in the dedifferentiation.

Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, S. Paratyphi A has been the major important causative factor in paratyphoid fever. An effective vaccine for S. Paratyphi A has not been developed, which made it a tricky public health concern. Until now, how S. Paratyphi A interacts with organisms remain unknown. Here using lifespan assay, we found that S. Paratyphi A could infect Caenorhabditis elegans (C. elegans) at 25°C, and attenuate thermotolerance. The immune response of C. elegans was mediated by tir-1, nsy-1, sek-1, pmk-1, mpk-1, skn-1, daf-2 and daf-16, suggesting that S. Paratyphi A could regulate the MAPK and insulin pathways. Furthermore, we observed several phenotypical changes when C. elegans were fed S. Paratyphi A, including an accelerated decline in body movement, reduced the reproductive capacity, shortened spawning cycle, strong preference for OP50, arrested pharyngeal pumping and colonization of the intestinal lumen. The virulence of S. Paratyphi A requires living bacteria and is not mediated by secreting toxin. Using hydrogen peroxide analysis and quantitative RT-PCR, we discovered that S. Paratyphi A could increase oxidative stress and regulate the immune response in C. elegans. Our results sheds light on the infection mechanisms of S. Paratyphi A and lays a foundation for drugs and vaccine development.

BackgroundMultiple clinical studies have indicated that the gut microbiota influences the effects of immune checkpoint blockade (ICB) therapy comprising PD-1/PD-L1 inhibitors, but the causal relationship is unclear. Because of numerous confounders, many microbes related to PD-1/PD-L1 have not been identified. This study aimed to determine the causal relationship between the microbiota and PD-1/PD-L1 and identify possible biomarkers for ICB therapy.MethodWe used bidirectional two-sample Mendelian randomization with two different thresholds to explore the potential causal relationship between the microbiota and PD-1/PD-L1 and species-level microbiota GWAS to verify the result.ResultIn the primary forward analysis, genus_Holdemanella showed a negative correlation with PD-1 [βIVW = -0.25; 95% CI (-0.43 to -0.07); PFDR = 0.028] and genus_Prevotella9 showed a positive correlation with PD-1 [βIVW = 0.2; 95% CI (0.1 to 0.4); PFDR = 0.027]; order_Rhodospirillales [βIVW = 0.2; 95% CI (0.1 to 0.4); PFDR = 0.044], family_Rhodospirillaceae [βIVW = 0.2; 95% CI (0 to 0.4); PFDR = 0.032], genus_Ruminococcaceae_UCG005 [βIVW = 0.29; 95% CI (0.08 to 0.5); PFDR = 0.028], genus_Ruminococcus_gnavus_group [βIVW = 0.22; 95% CI (0.05 to 0.4); PFDR = 0.029], and genus_Coprococcus_2 [βIVW = 0.4; 95% CI (0.1 to 0.6); PFDR = 0.018] were positively correlated with PD-L1; and phylum_Firmicutes [βIVW = -0.3; 95% CI (-0.4 to -0.1); PFDR = 0.031], family_ClostridialesvadinBB60group [βIVW = -0.31; 95% CI (-0.5 to -0.11), PFDR = 0.008], family_Ruminococcaceae [βIVW = -0.33; 95% CI (-0.58 to -0.07); PFDR = 0.049], and genus_Ruminococcaceae_UCG014 [βIVW = -0.35; 95% CI (-0.57 to -0.13); PFDR = 0.006] were negatively correlated with PD-L1. The one significant species in further analysis was species_Parabacteroides_unclassified [βIVW = 0.2; 95% CI (0-0.4); PFDR = 0.029]. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analyses confirmed the robustness of the MR results.

Abstract Objective By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center. Methods This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan–Meier method. Results For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%). Conclusions This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications’ morbidity, and acceptable long-term oncologic results.

BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

Exercise can help inhibition of neuropathic pain (NP), but the related mechanism remains being explored. In this research, we performed the effect of swimming exercise on the chronic constriction injury (CCI) rats. Compared with CCI group, the mechanical withdrawal threshold of rats in the CCI-Swim group significantly increased on the 21st and 28th day after CCI surgery. Second-generation RNA-sequencing technology was employed to investigate the transcriptomes of spinal dorsal horns in the Sham, CCI, and CCI-Swim groups. On the 28th day post-operation, 306 intersecting long non-coding RNAs (lncRNAs) and 173 intersecting mRNAs were observed between the CCI vs Sham group and CCI-Swim vs CCI groups. Then, the biological functions of lncRNAs and mRNAs in the spinal dorsal horn of CCI rats were then analyzed. Taking the results together, this study could provide a novel perspective for the treatment for NP.

With regard to the user privacy leakage problem in existing logistics systems,a privacy-preserving scheme for logistics systems based on 2D code and information hiding was proposed.The information hiding tech-nique was used in the proposed scheme to embed the user privacy information into the 2D code on the logistics waybill to achieve access control.To secure the user privacy information,a JPEG image stenographic algorithm for 2D code was designed.Experimental results demonstrate that this algorithm can guarantee the high undetectable performance and the stego 2D code can be correctly decoded.Using the proposed scheme,the institution or the per-son that has the access right can obtain the important privacy information so that the express can be delivered cor-rectly and the user privacy can be preserved.

In the research of state-of-the-art steganography algorithms,most of image sources were natural images in laboratory environment.However,with the rapid development of image process tools and applications,images after image processing were widely used in real world.How to use image process to improve steganography has not been systematically studied.Taking spatial image transform for consideration,a parameters’ disturbance model was presented,which could hide the noise taken by steganography in the pixel fluctuation due to the disturbance.Meanwhile,it would introduce cover source mismatch for a steganalyzer.The experimental results show that,compared with using traditional image database,it can significantly enhance the security of steganography algorithms and accommodative to the real world situation.

The additions of straw and biochar have been suggested to increase soil fertility, carbon sequestration, and crop productivity of agricultural lands. To our knowledge, there is little information on the effects of straw and biochar addition on soil nitrogen form, carbon storage, and super rice yield in cold waterlogged paddy soils. We performed field trials with four treatments including conventional fertilization system (CK), straw amendment 6 t ha−1 (S), biochar amendment 2 t ha−1 (C1), and biochar amendment 40 t ha−1 (C2). The super japonica rice variety, Shennong 265, was selected as the test crop. The results showed that the straw and biochar amendments improved total nitrogen and organic carbon content of the soil, reduced N2O emissions, and had little influence on nitrogen retention, nitrogen density, and CO2 emissions. The S and C1 increased NH4+-N content, and C2 increased NO3−-N content. Both S and C1 had little influence on soil organic carbon density (SOCD) and C/N ratio. However, C2 greatly increased SOCD and C/N ratio. C1 and C2 significantly improved the soil carbon sequestration (SCS) by 62.9 and 214.0% (P

In the real world, reducing false positive rates in the case of cover source mismatch (CSM) was a big challenge for steganalysis. A novel model was proposed to solve the problem. The proposed method determines the im-age-acquiring source firstly by a source detector and then detecting the steg images in each source with a steganalyzer trained for this source. The false positive rate was reduced by solving a parameter model. The experimental results show that this novel method can reach lower false positive rates for larger true positive rates.

Reversible data hiding methods can recover the cover image losslessly after extracting the secret message from the marked image.Such technology can be used in the certification or the label of military,justice and medical images,which are sensitive and slight modification are not allowed.Especially for the medical images,RDH tech-nology can be used in protecting the privacy of the patient.A series of RDH methods with contrast enhancement ef-fect were introduced and classified into pixel-based histogram methods and prediction-error-based histogram meth-ods according to the type of carrier in RDH scheme.The main purpose of such algorithms was to improve the sub-jective visual quality of marked images and to embed secret data into cover image reversibly meanwhile.These se-ries of algorithms were suitable for the research of privacy protection of medical image.Finally,future development in this direction is prospected through analyzing the advantages and disadvantages of the existing work.

Most reversible data hiding (RDH) techniques have been evaluated by PSNR,which is based on MSE.Unfortunately,MSE turns out to be an extremely poor measure when the purpose is to predict perceived signal fidel-ity or quality.The structural similarity index has gained widespread popularity as an alternative motivating principle for the design of image quality measures.How to utilize the characterize of SSIM to design RDH algorithm is very critical.An optimal RDH algorithm under structural similarity constraint was proposed.Firstly,the metric of the structural similarity constraint was deduced.Secondly,the rate-distortion function of optimal structural similarity constraint was constructed,which was equivalent to minimize the average distortion for a given embedding rate.Fi-nally,the optimal transition probability matrix under the structural similarity constraint was obtained.Experiments show that the proposed method can be used to improve the performance of previous RDH schemes evaluated by SSIM.

Objective To observe the rehabilitation effect of modified constraint-induced movement therapy (mCIMT) on activities of daily living (ADL) in patients with acute ischemic stroke. Methods A total of 60 patients in acute stage of cerebral stroke with limb dysfunction admitted in Ruijin Hospital from December 2012 to May 2013, were randomly divided into routine rehabilitation treatment group (control group, N = 30) and mCIMT group (N = 30). Control group was given routine rehabilitation training, 60 min each time, twice per day, 5 d per week; mCIMT group received mCIMT treatment with the similar frequency. After 2-week training, all patients were transferred to rehabilitation center for 4-week continous training. The total treatment period was 6 weeks. All of those patients received assessment before treatment and 2 weeks, 6 weeks, 12 weeks after treatment on the ability of daily living and motor function, including the modified Barthel Index (mBI), Fugl-Meyer Assessment (FMA) and Berg Balance Scale (BBS). Results Patients in both groups got increased mBI (P = 0.004, 0.000, 0.000), FMA (upper limb: P = 0.000, for all) and BBS scores (P = 0.005, 0.000, 0.000) 2, 6, 12 weeks after treatment. FMA (lower limb) score was increased 6 and 12 weeks after treatment (P = 0.000, for all). Compared to the control group, patients in mCIMT group got increased mBI (P = 0.000, for all), FMA (upper limb: P = 0.000, for all; lower limb: P = 0.000, for all) and BBS scores (P = 0.000, for all) 2, 6, 12 weeks after treatment. Conclusions mCIMT has positive therapeutic effects on the motor function of limbs in hemiplegic patients with stroke in acute stage, which can improve the balance ability and the ability of daily life, so as to raise the quality of life of patients. The efficacy of mCIMT is superior to general routine rehabilitation treatment. DOI: 10.3969/j.issn.1672-6731.2015.04.006

A novel clustering algorithm for wireless sensor networks was proposed to resolve the hot spot problem and the single failure problem.The algorithm divided the network into unequal grids,and the nodes in the same grid form a cluster.The number of cluster heads in each grid was determined according to the failure probability of nodes,and the data collection of nodes in a grid was implemented by multiple cluster heads of the grid cooperatively.By adjusting the number of nodes that could participate in cluster head rotation of each grid,the algorithm was able to balance the energy dissipation of nodes on a long view.The algorithm reduced the reliance of cluster members to single cluster head by forming cluster with multiple cluster heads.Furthermore,the algorithm adopted some measures to diminish energy consumption.Simulation results show that the algorithm has higher balanced extent of energy dissipation and reliability of data collection,and prolongs the lifetime of network.

Researches on the problem that the existing data fusion algorithms couldn't satisfy the new application re-quirements,ie,frequent dynamic change of network and hi demand with reliability of data communication,a struc-ture-free and dynamic-adaptive data fusion algorithm was presented which divided the network into several grids,sensors perform data communication according to grids and adopt many-to-many data communication manner,there was no need for sensors to establish and maintain a structure.The results of simulation experiments show that this algorithm is able to adapt the dynamic change of network and offer high reliable data communication while performs the task of data fusion.

Based on an information theory model,the cryptographic security of matrix encoding,which can be applied in steganographic codes or wet paper codes,under different attack conditions was studied.The cryptographic security about matrix encoding under the condition of known-cover attack with key equivocation,message equivocation and unicity distance of stego-key was presented.The result that n groups of differential equations could sufficiently recover the share key of matrix encoding under the condition of chosen-stego attack was pointed out.

BACKGROUND: Stanniocalcin-1 (STC1) and stanniocalcin-2 (STC2) are secreted glycoprotein hormones involved in various types of human malignancies. The roles of STC1 and STC2 in laryngeal squamous cell carcinoma (LSCC) remain unknown. We investigated correlations between STC1 and STC2 expression and clinicopathological or prognostic factors in LSCC. METHODS: Pre-surgical peripheral blood samples were collected between 2012 and 2013 from 62 patients with LSCC. Quantitative RT-PCR analysis was performed to examine mRNA levels of STC1 and STC2. Immunohistochemistry was performed to retrospectively analyze 90 paraffin-embedded LSCC tissue samples, which were obtained from patients who received surgery between 2006 and 2009. These patients did not have histories of treatment or malignancies. Univariate analysis of patient survival was performed by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards model. RESULTS: The relative mRNA levels of STC1 and STC2 in peripheral blood were significantly greater in LSCC patients than those of healthy volunteers (both P

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1α inhibition and strengthened by HIF-1α stabilization. OBJECTIVE: To elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR). METHODS: Mice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl(2)) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1α and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated. RESULTS: HIF-1α and VEGF levels were locally up-regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge, including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment, up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA-specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively inhibited HIF-1α and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1α by CoCl(2) facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice. CONCLUSIONS: HIF-1α is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1α may be useful as a novel therapeutic approach for AR.

The adsorption behaviour of three aromatic acids [phenol, benzoic acid (BCA) and 2-naphthalene sulphonic acid (2-NSA)] and of one aromatic base (aniline) on an aminated macroreticular adsorbent (NDA103) were investigated employing single or binary batch systems at 293 K and 313 K, respectively. All the adsorption isotherms in the studied systems could be adequately fitted by the Langmuir model, thereby indicating the existence of an exothermic adsorption process for phenol, BCA and aniline. At low equilibrium concentrations, the individual uptakes in the single-component systems were higher than those in binary-component systems because of competition between the two types of adsorbate molecules towards the adsorption sites. On the other hand, it is noteworthy that the total molar uptakes of adsorbates in the binary-component systems at high equilibrium concentrations were larger than the uptakes in the single-component systems. In binary-component systems, a large excess of aromatic acids was noted on the adsorbent surface at saturation, presumably as a result of a cooperative effect arising primarily from acid–base interaction between the loaded adsorbates.

Numerous agents such as near-infrared dyes that are characterized by specialized cancer imaging and cytotoxicity effects have key roles in cancer diagnosis and therapy via molecularly targeting special biological tissues, organelles and processes. In the present study, a novel fluorescent compound was demonstrated to inhibit cancer cell proliferation in a zebrafish model with slight in vivo toxicity. Further studies demonstrated selective staining of cancer cells and even putative cancer stem cells via accumulation of the dye in the mitochondria of cancer cells, compared with normal cells. Moreover, this compound was also used to image cancer cells in vivo using a zebrafish model. The compound displayed no apparent toxicity to the host animal. Overall, the data indicated that this compound was worthy of further evaluation due to its low toxicity and selective cancer cell imaging and killing effects. It could be a useful tool in cancer research. [ABSTRACT FROM AUTHOR]