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BACKGROUND: The aim of our study was to examine the impact of the combination of the ratio between metastatic and harvested lymph nodes (RML) and negative lymph node (NLN) count on overall survival (OS) in patients with advanced gastric cancer (GC). METHODS: The clinicopathological data of 2,952 advanced GC patients who received curative resection between 1994 and 2015 were collected. They were divided into four groups according to the RML: 0, 0–0.1, 0.1–0.4, and >0.4. We distinguished survival differences through Kaplan-Meier analysis among the subgroups to investigate the impacts of the RML on OS in advanced GC patients. OS was examined according to clinicopathological variables. Spearman’s correlation coefficient was used to assess the relationships between the RML and metastatic lymph node (MLN) count and NLN count. RESULTS: A total of 1,182 patients were enrolled into the study. The median follow-up time was 39 months (interquartile range 20 to 68 months). The 5-year OS rate of all 1,182 GC patients was 54.4%. Kaplan-Meier survival analysis showed that the median OS declined significantly with increasing RML (5-year survival rate 81.2% vs. 69.1% vs. 42.8% vs. 13.1%, P

There are unmet clinical needs for novel therapeutic targets and drugs for bladder cancer. Majority of previous work relied on limited bladder cancer cell lines, which could not well represent the tumor heterogeneity and pathology of this disease. Recently, it has been shown that cancer organoids can recapitulate pathological and molecular properties of bladder cancer. Here, we report, by our knowledge, the first bladder cancer organoid-based small molecule screening for epigenetic drugs. We found that SRT1720, a Sirtuin 1 (SIRT1) activator, significantly inhibits the growth of both mouse and human bladder cancer organoids. And it also restrains the development of mouse in situ bladder cancer and human PDX bladder cancer. Mutation of Sirt1 promotes the growth of cancer organoids and decreases their sensitivity to SRT1720, which validate Sirt1 as the target of SRT1720 in bladder cancer. Mechanistically, SRT1720 treatment represses the hypoxia pathway through deacetylating HIF1α by activating Sirt1. Genetic or pharmaceutic inhibitions of HIF mimic the anti-tumor effect of SRT1720. Furthermore, the SIRT1-repressed gene signature is associated with the hypoxia target gene signature and poor prognosis in human bladder cancers. Thus, our study demonstrates the power of cancer organoid-based drug discovery and, in principle, identifies SRT1720 as a new treatment for bladder cancer.

Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large‐scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large‐scale inter‐ and intranetwork functional connectivity was measured using a combination of resting‐state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota‐brain‐behavior relationships from the perspective of large‐scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota., Gut microbiota can modulate large‐scale inter‐ and intranetwork functional connectivity (especially the executive control system) in young adulthood. Some functional network connectivity may act as mediators of the effects of gut microbiota on sleep and executive functions.

Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders.

ObjectivesFamilial aggregation of primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined.MethodsWe used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic byin silicoanalysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets.ResultsA range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10−7) and T cell receptor (TCR) signalling pathway (p=1.73×10−6) were particularly concentrated, includingPTPRC(CD45),LCK,LAT–SLP76complex genes (THEMIS,LAT,ITK,TEC,TESPA1,PLCL1),DGKD,PRKD1,PAK2andNFAT5, shared across 14 SLE, RA and pSS families. TCR-interactive genesP2RX7,LAG3,PTPN3andLAX1were also detected. Overlap analysis demonstrated that the antiviral immunity geneDUS2variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genesCD45,LCKandPRKD1occurred independently in three mixed autoimmunity families, and that variants inCD36andVWA8occurred in both RA-pSS and SLE-pSS families.ConclusionsOur preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs.

Psychological stress may be linked to cancer incidence; however, more direct evidence is required to support this viewpoint. In this study, we investigated the effects of stress on immunosurveillance against cancer cells using a previously established examination stress model. We showed that the cancer killing activity (CKA) of granulocytes (also known as polymorphic nuclear cells, PMNs) is sharply reduced during examination stress stimulation in some donors who are psychologically sensitive to examination stress, with the concentration of plasma stress hormones (cortisone, epinephrine, and norepinephrine) increasing accordingly. The effects of stress hormones on immune cell CKA were also investigated under two in vitro co-incubation conditions, with all three hormones found to exert inhibitory effects on the CKA of PMNs and mononuclear cells. We showed that stress triggered the release of stress hormones which had profound inhibitory effects on the innate anticancer functions of PMNs. These results provide a possible explanation for the relationship between psychological stress and cancer incidence.

Background Gallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy. Long noncoding RNAs (lncRNAs) function as critical regulators of multiple stages of cancers. Herein, the mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in GBC is investigated. Methods Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up-regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Kaplan-Meier method was then adopted to analyze the relationship between the MALAT1 expression and overall survival and disease-free survival of patients with GBC. A set of in vitro and in vivo experiments were conducted by transducing ABI3BP-vector or sh-MALAT1 into GBC cells. Results The results confirmed that the cancer prevention effects triggered by restored ABI3BP and depleted MALAT1 as evidenced by suppressed cell growth and enhanced cell senescence. MALAT1 was observed to down-regulate ABI3BP expression through recruitment of the enhancer of zeste homolog 2 (EZH2) to the ABI3BP promoter region while the silencing of MALAT1 or suppression of H3K27 methylation was observed to promote the expression of ABI3BP. Furthermore, GBC patients with high expression of MALAT1 indicated poor prognosis. Conclusion The current study clarifies that MALAT1 silencing and ABI3BP elevation impede the GBC development through the H3K27 methylation suppression induced by EZH2, highlighting a promising competitive paradigm for therapeutic approaches of GBC.

It has been a long-standing challenge to obtain from cell cultures adequate amounts of mouse corneal epithelial cells (mCEC) to perform transplantation surgery. This limitation is attributable to the passage dependent declines in their proliferative activity. We describe here development of a novel 6C medium that contains six different modulators of different signaling pathways, which control proliferative mCEC activity. Its usage shortens the time and effort required to obtain epithelial sheets for hastening healing of an epithelial wound in an experimental animal model. This serum-free 6C medium contains:Y27632, forskolin, SB431542, DAPT, IWP-2, LDN-193189 and also DermaLife K keratinocyte calcium. Their inclusion inhibits rises in four specific markers of epithelial mesenchymal transdifferentiation:ZEB1/2, Snail, β-catenin and α-SMA. This medium is applied in a feeder-free air-lifted system to obtain sufficient populations of epithelial progenitor cells whose procurement is facilitated due to suppression of progenitor epithelial cell transdifferentiation into epithelial-mesenchymal cells. Diminution of this decline in transdifferentiation was confirmed based on the invariance of P63, K14, Pax6, and K12 gene expression levels. This cell culture technique is expected to facilitate ex vivo characterization of mechanisms underlying cell fate determination. Furthermore, its implementation will improve yields of progenitor mouse corneal epithelial cells, which increases the likelihood of using these cells as a source to generate epithelial sheets for performing transplantation surgery to treat limbal stem cell deficiency in a clinical setting. In addition, the novel insight obtainable from such studies is expected to improve the outcomes of corneal regenerative medicine.

Purpose Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key pathological event in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). This study aimed to explore a new method to reverse EMT in RPE cells to develop an improved therapy for proliferative retinal diseases. Methods In vitro, human embryonic stem cell-derived RPE cells were passaged and cultured at low density for an extended period of time to establish an EMT model. At different stages of EMT after treatment with known molecules or combinations of molecules, the morphology was examined, transepithelial electrical resistance (TER) was measured, and expression of RPE- and EMT-related genes were examined with RT-PCR, Western blotting, and immunofluorescence. In vivo, a rat model of EMT in RPE cells was established via subretinal injection of dispase. Retinal function was examined by electroretinography (ERG), and retinal morphology was examined. Results EMT of RPE cells was effectively induced by prolonged low-density culture. After EMT occurred, only the combination of the Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y27632 and the TGF-β receptor inhibitor RepSox (RY treatment) effectively suppressed and reversed the EMT process, even in cells in an intermediate state of EMT. In dispase-treated Sprague-Dawley rats, RY treatment maintained the morphology of RPE cells and the retina and preserved retinal function. Conclusions RY treatment might promote mesenchymal-epithelial transition (MET), the inverse process of EMT, to maintain the epithelial-like morphology and function of RPE cells. This combined RY therapy could be a new strategy for treating proliferative retinal diseases, especially those involving EMT of RPE cells.

Background: Previous neuroimaging studies have demonstrated brain abnormalities in patients with hepatic diseases. However, the identified liver–brain associations are largely limited to disease-affected populations, and the nature and extent of such relations in healthy subjects remain unclear. We hypothesized that serum liver function markers within a normal level would affect brain properties.Method: One hundred fifty-seven healthy young adults underwent structural, resting-state functional, and arterial spin labeling MRI scans. Gray matter volume (GMV), regional homogeneity (ReHo), and cerebral blood flow (CBF) analyses were performed to assess brain structure, function, and perfusion, respectively. Peripheral venous blood samples were collected to measure serum liver function markers. Correlation analyses were conducted to test potential associations between liver function markers and brain imaging parameters.Results: First, serum proteins showed relations to brain structure characterized by higher albumin associated with increased GMV in the parahippocampal gyrus and amygdala and lower globulin and a higher albumin/globulin ratio with increased GMV in the olfactory cortex and parahippocampal gyrus. Second, serum bilirubin was linked to brain function characterized by higher bilirubin associated with increased ReHo in the precuneus, middle cingulate gyrus, inferior parietal lobule, and supramarginal gyrus and decreased ReHo in the caudate nucleus. Third, serum alanine transaminase (ALT) was related to brain perfusion characterized by higher ALT associated with increased CBF in the superior frontal gyrus and decreased CBF in the middle occipital gyrus, angular gyrus, precuneus, and middle temporal gyrus. More importantly, we found that CBF in the superior frontal gyrus was a significant mediator of the association between serum ALT level and working memory performance.Conclusion: These findings may not only expand existing knowledge about the relationship between the liver and the brain but also have clinical implications for studying brain impairments secondary to liver diseases as well as providing potential neural targets for their diagnosis and treatment.

Background: Gastric cardia cancer (GCC) arises in the area of the stomach adjoining the esophageal–gastric junction and has unique risk factors. It was suggested that the involvement of Helicobacter pylori is associated with GCC from high-risk population. Myeloid differentiation factor 88 (MyD88) is a crucial adaptor molecule in Toll-like signaling pathway recognizing H. pylori. Its role in GCC has not been elucidated yet. In this study, our purpose is to investigate the expression and significance of MyD88 in GCC tissue. Methods: Expression of MyD88 and nuclear factor κB (NF-κB) p105/p50 and infection of H. pylori were detected by immunohistochemistry in gastric cardia tissue. The correlation of MyD88 expression to NF-κB p105/p50 expression, H. pylori infection, and clinicopathologic characteristics in gastric cardia tissue was analyzed. The involvement of MyD88 in patient prognosis was also analyzed. Results: Our data showed that the expression of MyD88 elevated from normal mucosa to inflammation (p = 0.071). The expression of MyD88 was enhanced in GCC tissues by contrast to non-malignant cardia mucosa (p = 0.025). What's more, overexpression of MyD88 was detected in intestinal-type adenocarcinoma with inflammation. Patients with high MyD88 staining revealed a better differentiation (p = 0.02). MyD88 also positively correlated with NF-κB p105/p50 expression (p = 0.012) in cancer tissue. Expression of MyD88 was increased but not significantly in biopsies with H. pylori infection compared with non-infected biopsies. Multivariate analyses revealed lymph node metastasis but not MyD88 expression was an independent predictor for patient survival. Conclusion: These findings provide pathological evidence that upregulating MyD88 and inducing inflammation might be involved in gastric cardia carcinogenesis in high-risk population. MyD88 plays a role in gastric cardia carcinogenesis with NF-κB pathway activation. Higher MyD88 expression is not a major prognostic determinant in GCC, but it may relate to the tumor cell differentiation.

Modulating the surface properties of nanoparticles (NPs) is an important approach to accomplish immune escape, prolonged the blood retention time, and enhance the ability of targeted drug delivery. The camouflage of cancer cell membrane onto nanoparticles has been proved to be an ideal approach to enhance active targeting ability of NPs. Herein, we isolated the membrane of melanoma cells to coat doxorubicin (DOX) and indocyanine green (ICG)-loaded hollow copper sulfide NPs (ID-HCuSNP@B16F10) for targeted photothermal therapy, photoacoustic imaging, and chemotherapy. A remarkable in vitro anticancer effect after irradiation and homologous targeting can be observed in B16F10 cells after the treatment of ID-HCuSNP@B16F10. Moreover, ID-HCuSNP@B16F10 exhibits excellent photothermal effect in melanoma animal models and achieves a high tumor ablation rate. This biomimetic system can realize high drug loading efficiency, enhanced targeting ability, and ideal antitumor efficiency.

Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.

Background: Hainan province is a very popular leisure tourist arriving city in China. Coronavirus disease 2019 (COVID-19) emerged in China and rapidly in early 2020, and due to its rapid worldwide spread, the World Health Organization declared COVID-19 as a global emergency. During the COVID-19 pandemic in Hainan province, many businesses and economies were influenced in this unexpected event, especially in tourism. Methods: This study used 2 classical forecasting methods to predict the number of tourists on Hainan Leisure Island from September to December in the second half of 2020 and to summarize the COVID-19 fighting experience during the pandemic. In addition, the Hainan government implemented epidemic control measures to resume production and work, and promote new tourism measures to acquire superior COVID-19 protection. Results: Winter's method provides a statistical model for predicting the number of visitors to Hainan under normal conditions. The trend analysis method considers the impact of the black swan event, an irregular event, and only uses the data under the influence of the event to predict according to the trend. Conclusion: If the impact of the black swan event (COVID-19) continues, the prediction can be made using this method. In addition, the Hainan government has undertaken timely and effective measures against COVID-19 to promote leisure tourism development.

BACKGROUND: The influence of pretreatment anemia on the prognosis of patients with advanced gastric cancer (GC) remains controversial. We retrospectively examined the impact of pretreatment anemia on the overall survival (OS) of patients with GC with nonhypoalbuminemia undergoing curative resection. METHODS: The clinicopathological data of 2,916 patients with advanced GC who received a radical gastrectomy from 1994 to 2015 were analyzed. The patients were divided into two subgroups by hemoglobin level

Extensive neuroimaging research has attempted to identify neural correlates and predictors of decision impulsivity. However, the nature and extent of decision impulsivity-brain association have varied substantially across studies, likely due to small sample sizes, limited image quality, different imaging measurement selections, and non-specific methodologies. The objective of this study was to develop a reliable predictive model of decision impulsivity-brain relationship in a large sample by applying connectome-based predictive modeling (CPM), a recently developed machine learning approach, to whole-brain functional connectivity data ("neural fingerprints"). For 809 healthy young participants from the Human Connectome Project, high-quality resting-state functional MRI data were utilized to construct brain functional connectome and delay discounting test was used to assess decision impulsivity. Then, CPM with leave-one-out cross-validation was conducted to predict individual decision impulsivity from whole-brain functional connectivity. We found that CPM successfully and reliably predicted the delay discounting scores in novel individuals. Moreover, different feature selection thresholds, parcellation strategies and cross-validation approaches did not significantly influence the prediction results. At the neural level, we observed that the decision impulsivity-associated functional networks included brain regions within default-mode, subcortical, somato-motor, dorsal attention, and visual systems, suggesting that decision impulsivity emerges from highly integrated connections involving multiple intrinsic networks. Our findings not only may expand existing knowledge regarding the neural mechanism of decision impulsivity, but also may present a workable route towards translation of brain imaging findings into real-world economic decision-making.

Significance It remains formidable to predict what unreported RNA pairs can form new fusion transcripts. By systematic mapping of chromatin-associated RNAs and their respective genomic interaction loci, we obtained genome-wide RNA–DNA interaction maps from two noncancerous cell types. The gene pairs involved in RNA–DNA interactions in these normal cells exhibited strong overlap with those with cancer-derived fusion transcripts. These data suggest an RNA-poise model, where the spatial proximity of one gene’s transcripts and the other gene’s genomic sequence poises for the creation of fusion transcripts. We validated this model with 96 additional lung cancer samples. One of these additional samples exhibited fusion transcripts without a corresponding fusion gene, suggesting that genome recombination is not a required step of the RNA-poise model., Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA–DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA–genome interactions (MARGI) assay]. Among the top 10 most significant RNA–DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA–DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA–DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA–DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest an RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.

Background: Dry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM. Methods: A total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P < 0.05. Results: In the severe symptom group, OSDI and SEEQ scores were significantly higher (P < 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P > 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P < 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild; P < 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P < 0.05). Conclusions: IVCM application provides a strong support to differentiate dry eye patients with different symptoms: meibomian gland dysfunction (MGD) plays a pivotal role in dry eye aggravation, and using IVCM to observe MG fibrosis, changes in size and density of MG as well as status of inflammation cells can help not only correctly diagnose the type and severity of dry eye, but also possibly prognosticate in routine eye examination in the occurrence of MGD.

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, non-cancerous cell types (using iMARGI, an enhanced version of the MARGI [Mapping RNA-Genome Interactions assay]). Among the top 10 most significant RNA-DNA interactions in normal cells, 5 co-localized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA-seq. 37 out of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest a novel RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.

Amniotic membrane (AM) has been widely used as a temporary or permanent graft in the treatment of various ocular surface diseases. In this study, we compared the epithelial wound healing and tissue remodeling after ocular surface reconstruction with intact amniotic membrane (iAM) or denuded amniotic membrane (dAM). Partial limbal and bulbar conjunctival removal was performed on New Zealand rabbits followed by transplantation of cryo-preserved human iAM or dAM. In vivo observation showed that the epithelial ingrowth was faster on dAM compared to iAM after AM transplantation. Histological observation showed prominent epithelial stratification and increased goblet cell number on dAM after 2 weeks of follow up. Collagen VII degraded in dAM within 2 weeks, while remained in iAM even after 3 weeks. The number of macrophages and α-SMA positive cells in the stroma of remodelized conjunctiva in the dAM transplantation group was considerably less. In conclusion, dAM facilitates epithelial repopulation and goblet cell differentiation, further reduces inflammation and scar formation during conjunctival and corneal limbal reconstruction.

The incidence of gastric cardia cancer (GCC) is high in China. However, the clinicopathological characteristics and the carcinogenesis of GCC are unclear. Toll-like receptor 4 (TLR4) is an important innate immunity receptor and has a role in non-GCC (NGCC). We compared the clinicopathological characteristics of GCC patients from a high-risk area in China to esophageal cancer (EC) patients. Immunohistochemistry for TLR4 was performed in 201 histological samples of normal gastric cardia mucosa (n=11), gastric cardia inflammation (n=87), and GCC (n=103). We included 84 patients with EC and 99 with GCC. GCC tissue was more poorly differentiated than EC tissue and more invasive, with more histomorphologic variation. Lymph node metastasis was more frequent in GCC than in EC. TheHelicobacter pyloriinfection rate was higher but not significantly with GCC than EC. Survival was shorter with lymph node metastasis. We found a statistically significant trend for progressive increase of TLR4 expression from normal mucosa to inflammation in GCC. GCC in this high-risk area displays clinicopathologic characteristics different from those of EC and different from those of gastroesophageal junction carcinomas in other countries, although this was not analyzed statistically. Increased TLR4 expression in gastric cardia lesions may be associated with GCC tumorigenesis.

Growing number of contact lens discomfort (CLD) and CL dropout incidence rate afflict the development of CL industry. This article analyzes literatures of past 5 years’ on studies of CLD. It reviews the epidemiology and mechanism of CLD, analyzes different characteristics of CLD resulting from CL material, contact lens care system, and wearers. It sketches the relationship between CLD and ocular surface microenvironment, pointing out that CLD is an incompatible status between CL and the ocular surface microenvironment. Literature analysis also reveals that while high-quality optical effect of rigid lens came at the price of unwelcome initial discomfort, soft lens wearing continuously changes the balance of ocular surface microenvironment, leading to time-dependent discomfort. Different components or formulas of contact lens care systems could be transited by CL into ocular surface and induce CLD. Personal features of wearers such as age, gender, race, and psychological state also could be considered as potential CLD risks.

Descemet’s membrane (DM) helps maintain phenotype and function of corneal endothelial cells under physiological conditions, while little is known about the function of DM in corneal endothelial wound healing process. In the current study, we performed in vivo rabbit corneal endothelial cell (CEC) injury via CEC scraping, in which DM remained intact after CECs removal, or via DM stripping, in which DM was removed together with CECs. We found rabbit corneas in the CEC scraping group healed with transparency restoration, while there was posterior fibrosis tissue formation in the corneas after DM stripping on day 14. Following CEC scraping on day 3, cells that had migrated toward the central cornea underwent a transient fibrotic endothelial-mesenchymal transition (EMT) which was reversed back to an endothelial phenotype on day 14. However, in the corneas injured via DM stripping, most of the cells in the posterior fibrosis tissue did not originate from the corneal endothelium, and they maintained fibroblastic phenotype on day 14. We concluded that corneal endothelial wound healing in rabbits has different outcomes depending upon the presence or absence of Descemet’s membrane. Descemet’s membrane supports corneal endothelial cell regeneration in rabbits after endothelial injury.

The soy protein hydrolysate subjected to selective proteolysis on β-conglycinin (referred to as DβH, contrast group) and a control soy protein isolate sample without addition of protease (referred to as CSPI, blank group) were adopted as experimental samples. By employing the "subtraction" mode of logical thinking, we aimed to compare the differences between CSPI and DβH on fibrillation at pH2.0 with heating at 95°C. The results showed when heated for 60min, CSPI tended to form short worm-like fibrils while DβH long semiflexible fibrils. When heating time was prolonged to 360min, the fibrils formed from them both exhibited cluster. Whereas when heated for 720min, no fibrillar aggregates appeared from them. This study would help explore the effects of β-conglycinin on the fibril formation of soy protein isolate by a new way.

Background: Poly(ADP-ribose) polymerase 1 (PARP1) plays an important role in the process of homologous recombination (HR) repair. The aim of this study was to observe the impact of olaparib (PARP1 inhibitor) on oxaliplatin treatment for XRCC2-defecient colorectal cancer (CRC). Methods: This study examined the influence of treatments on cells with the help of the γ-H2AX foci formation assay. The CCK-8 assay and clonogenic assay were employed to decide the sensitivity of XRCC2-defecient CRC cells to olaparib and/or oxaliplatin. Finally, we investigated the changes in cell cycle and apoptosis with the aid of flow cytometry and western blotting. Results: Gamma-H2AX focusing analysis has reached the conclusion that Olaparab is not the only factor inducing double-strand breaks (DSBs), but it can affect oxaliplatin-induced DSBs of XRCC2-defatted CRC cells. Cell proliferation of XRCC2-defecient CRC cell lines was restrained by combination treatment rather than olaparib or oxaliplatin alone. The flow cytometry and western blotting results gave the description cells exposed to connection treatment had more G2/M-phase cells and induced apoptosis than control. Conclusions: The combination of oxaliplatin and oxaliplatin in the treatment of XRCC2-defecient CRC cells provides a promising method for clinical treatment of XRCC2-defecient CRC.

Metastatic pancreatic tumor is relatively rare in clinic, accounting for only 2–5% of pancreatic cancer. About 50% of metastatic pancreatic tumor are caused by renal cell carcinoma. The symptoms of the tumor have no specificity but strong concealment. Most patients show no difference from ordinary population before the disease worsens. A small number of patients may have abdominal distention and pain, poor appetite, etc. Besides, there may be obstructive jaundice when the tumor blocks the common bile duct, and it can cause pancreatitis in the case of pancreatic duct obstruction. The case to be reported was asymptomatic and a mass of the head of the pancreas was found on examination. The diagnosis of this case depends mainly on ultrasound puncture to obtain pathological results, and CT can exert auxiliary effect during diagnosis. In addition, surgical resection is an effective means to treat this disease, and targeted therapy can be accepted as an alternative therapeutic approach.

Human amniotic membrane (AM) is avascular but contains various beneficial bioactive factors, its extract (AE) is also effective in treating many ocular surface disorders. In this study, we for the first time evaluated the therapeutic effects of AE on dry eye induced by benzalkonium chloride in a BALB/c mouse model. Topical application of AE (1.5 and 3 μg/eye/day) resulted in significantly longer tear break-up time on Day 3 and 6, lower fluorescein staining scores on Day 3, and lower inflammatory index on Day 6. AE reduced corneal epithelial K10 expression, inflammatory infiltration, and levels of TNF-α, IL-1β and IL-6 in BAC treated mice than that in the control mice. Moreover, decreased TUNEL positive cells in cornea and increased goblet cells in conjunctiva were also observed in AE treated corneas. Finally, AE induced more Ki-67 positive cells in corneal epithelium of dry eye mouse. Taken together, our data provide further support for BAC induced dry eye model as a valuable for dry eye study and suggest a great potential for AE as a therapeutic agent in the clinical treatment of dry eye.

Solitary fibrous tumour (SFT) is an uncommon neoplasm of mesenchymal origin that primarily affects the pleura and mediastinum. SFTs may occur elsewhere in the body including the liver, peritoneum, orbit and other soft tissues. Recent advances in immunohistochemical analysis have allowed greater identification of SFTs. Nevertheless, radiologically it remains difficult to distinguish SFTs of the liver from other solitary tumours as they have many common features. We report a case of SFT of the liver and highlight the potential inaccuracy of percutaneous biopsy in the diagnosis of large solitary liver tumours.