A clinical study of topical treatment for thyroid-associated ophthalmopathy with dry eye syndrome.

INTRODUCTION: Clinically, thyroid-associated ophthalmopathy (TAO) patients were suffered from dry eye syndrome. Only a few relevant studies were about this topic. Our study was determined to provide high-level evidence for the treatment of TAO with dry eye syndrome. PURPOSE: To compare the clinical effects of vitamin A palmitate eye gel and sodium hyaluronate eye drop forTAO patients with dry eye syndrome. METHODS: The study was conducted in the Ophthalmology Department of the Ninth People's Hospital Affiliated with the Medical College of Shanghai Jiao Tong University from May to October 2020. A total of 80 mild or moderate-to-severe TAO patients with dry eye syndrome were randomly divided into two groups. The disease stages of all subjects were inactive. Patients in group A were treated with vitamin A palmitate eye gel three times/day for one month and sodium hyaluronate eye drop in group B. The index including break-up time (BUT) and Schirmer I test (ST), corneal fluorescence staining (FL), ocular surface disease index (OSDI), and adverse reactions were recorded by the same clinician at baseline and 1 month after treatment. The data were analyzed by SPSS 24.0. RESULTS: Finally, 65 subjects completed the treatment. The average age of the patients in Group A was 38.1 ± 11.4 years, and that in Group B was 37.26 ± 10.67 years. 82% of the subjects in group A were female and 74% in group B. There was no significant difference between the two groups at baseline, including the value of ST, BUT, OSDI, and FL grade. After the treatment, the effective rate was 91.2% in group A, of which the value of BUT and FL grade was significantly improved (P < 0.001). The effective rate in group B was 67.7%, of which the value of OSDI score and FL grade was significantly improved (P = 0.002). In addition, the BUT value of group A was significantly longer than that of group B (P = 0.009). CONCLUSION: InTAO patients with dry eye syndrome, vitamin A palmitate gel and sodium hyaluronate eye drop improved the dry eye and promoted corneal epithelial repair. Vitamin A palmitate gel improves the stability of tear film, while sodium hyaluronate eye drop improves patients' subjective discomfort.

The Impact of Perceived Personal Discrimination on Migrant Students' Social Integration: The Mediating Effect of Group Permeability and Moderating Effect of Parental Involvement.

This study aimed to investigate how migrant students' group permeability and parental involvement affect the relationship between perceived personal discrimination and social integration. A total of 755 migrant students at three schools in mainland China were investigated in the study. The results indicated that perceived personal discrimination negatively predicted migrant students' group permeability, whereas group permeability had a positive effect on social integration. Group permeability partially mediated the relationship between perceived personal discrimination and social integration. In addition, parental involvement played a significant moderating role between perceived personal discrimination and group permeability and mitigated the negative effect of perceived personal discrimination on group permeability. These findings suggest that we could reduce migrant students' perceived personal discrimination by improving their group permeability and parental involvement, thereby increasing their social integration.

Detection of active and inactive phases of thyroid-associated ophthalmopathy using deep convolutional neural network.

BACKGROUND: This study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations. METHODS: A total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People's Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks. RESULTS: Network A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021). CONCLUSIONS: The deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.

A Novel Anti-classification Approach for Knowledge Protection.

Classification is the problem of identifying a set of categories where new data belong, on the basis of a set of training data whose category membership is known. Its application is wide-spread, such as the medical science domain. The issue of the classification knowledge protection has been paid attention increasingly in recent years because of the popularity of cloud environments. In the paper, we propose a Shaking Sorted-Sampling (triple-S) algorithm for protecting the classification knowledge of a dataset. The triple-S algorithm sorts the data of an original dataset according to the projection results of the principal components analysis so that the features of the adjacent data are similar. Then, we generate noise data with incorrect classes and add those data to the original dataset. In addition, we develop an effective positioning strategy, determining the added positions of noise data in the original dataset, to ensure the restoration of the original dataset after removing those noise data. The experimental results show that the disturbance effect of the triple-S algorithm on the CLC, MySVM, and LibSVM classifiers increases when the noise data ratio increases. In addition, compared with existing methods, the disturbance effect of the triple-S algorithm is more significant on MySVM and LibSVM when a certain amount of the noise data added to the original dataset is reached.

Cidea is associated with lipid droplets and insulin sensitivity in humans.

Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.

The Prognostic Value of Preoperative Geriatric Nutritional Risk Index in Patients with Pancreatic Ductal Adenocarcinoma.

PURPOSE: Patients with malignancy are more likely to develop nutritional problems. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic index for evaluating nutritional status. The objective of this study was to assess if preoperative GNRI could be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical surgery. PATIENTS AND METHODS: This study included 282 consecutive patients with incident pancreatic ductal adenocarcinoma who were treated with radical surgery. The Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors. A nomogram was developed based on the results of the multivariate analysis, and the predictive accuracy of the nomogram was assessed. RESULTS: Among the 282 patients, there are 117 males and 165 females. The patients had a mean age of 58.7 ±13.5 years, with the median follow-up time of 72.9 months (interquartile range, 0.7 to 115.2 months). They were classified into abnormal (GNRI ≤ 98) and normal (GNRI > 98) GNRI groups, respectively. Multivariate Cox analysis showed that age (HR = 1.023), drinking history (HR = 1.453), tumor grade (HR = 1.633), TNM stage (HR = 1.921), and GNRI (HR = 1.757) were significantly associated with OS. Based on the above variables, the nomogram was established. The concordance index (C-index) and time-dependent receiver operating characteristics curve (tdROC) showed the nomogram was superior to TNM grade and tumor grade in predicting the OS of patients with PDAC. CONCLUSION: GNRI could be a useful prognostic indicator in patients with PDAC who received surgery. Based on the GNRI and the other clinical indicators, we developed a nomogram model that can provide an accurate estimation of OS in patients with PDAC after radical surgery.

Low BRCA2 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy.

OBJECTIVE: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is now the standard care for patients with advanced rectal cancer. Because a certain proportion of these patients have poor response to CCRT, the risk stratification of survival outcomes needs to be investigated. DNA repair responses in tumor cells can regulate malignant potential and therapy resistance. In this study, we analyzed the clinical significance of principal DNA repair effectors in patients with rectal cancer. METHODS: We applied data mining for DNA repair pathways in a published transcriptome for rectal cancer cases, and identified that tumors with BRCA2 downregulation correlated with poor response to CCRT. We next examined BRCA2 expression by using immunohistochemistry staining in tumor tissues of 172 patients with rectal cancer. The correlation between BRCA2 expression levels and clinical variables was further analyzed in this rectal cancer cohort. RESULTS: Among clinical and pathological factors, low BRCA2-expression was significantly correlated with higher pre-treatment (Tx) tumor status (P = .013), post-Tx tumor (P < .001) and nodal status (P = .044), vascular invasion (P = .008), and poor tumor regression grades (P < .001). In analyses of survival outcomes, patients with low BRCA2-expression were associated with shorter local recurrence-free survival (LRFS; P = .0005) and disease-specific survival (P = .0269). Multivariate analyses confirmed the independent prognostic value of low BRCA2-expression for shorter LRFS (P = .045, hazard ratio = 4.695). CONCLUSION: Low BRCA2-expression is a significant predictor for tumors in advanced stages, poor response to CCRT, and shorter survivals in patients with rectal cancer. Poly (adenosine diphosphate-ribose) polymerase inhibitors targeting DNA repair response in cells have demonstrated clinical efficacy in BRCA2-mutated patients with cancer. Further studies evaluating the efficacy of CCRT combined with these inhibitors in low BRCA2-expressing rectal cancers are encouraged.

RcsB regulation of the YfdX-mediated acid stress response in Klebsiella pneumoniae CG43S3.

In Klebsiella pneumoniae CG43S3, deletion of the response regulator gene rcsB reduced the capsular polysaccharide amount and survival on exposure to acid stress. A comparison of the pH 4.4-induced proteomes between CG43S3 and CG43S3ΔrcsB revealed numerous differentially expressed proteins and one of them, YfdX, which has recently been reported as a periplasmic protein, was absent in CG43S3ΔrcsB. Acid survival analysis was then conducted to determine its role in the acid stress response. Deletion of yfdX increased the sensitivity of K. pneumoniae CG43S3 to a pH of 2.5, and transforming the mutant with a plasmid carrying yfdX restored the acid resistance (AR) levels. In addition, the effect of yfdX deletion was cross-complemented by the expression of the periplasmic chaperone HdeA. Furthermore, the purified recombinant protein YfdX reduced the acid-induced protein aggregation, suggesting that YfdX as well as HdeA functions as a chaperone. The following promoter activity measurement revealed that rcsB deletion reduced the expression of yfdX after the bacteria were subjected to pH 4.4 adaptation. Western blot analysis also revealed that YfdX production was inhibited by rcsB deletion and only the plasmid expressing RcsB or the nonphosphorylated form of RcsB, RcsBD56A, could restore the YfdX production, and the RcsB-mediated complementation was no longer observed when the sensor kinase RcsD gene was deleted. In conclusion, this is the first study demonstrating that YfdX may be involved in the acid stress response as a periplasmic chaperone and that RcsB positively regulates the acid stress response partly through activation of yfdX expression. Moreover, the phosphorylation status of RcsB may affect the YfdX expression under acidic conditions.

Higher nuclear EGFR expression is a better predictor of survival in rectal cancer patients following neoadjuvant chemoradiotherapy than cytoplasmic EGFR expression.

The aim of the present study was to investigate the prognostic value of cytoplasmic (-C) and nuclear epidermal growth factor receptor (EGFR-N) expression in rectal cancer patients following neoadjuvant concurrent chemoradiotherapy (CCRT). A total of 172 newly diagnosed rectal cancer patients post-neoadjuvant CCRT and curative surgery, treated between January 1998 to December 2008, were included. Pathological tissues used for evaluation were biopsy specimens obtained prior to CCRT, and specimens collected at surgery. EGFR expression in the nucleus and cytoplasm was assessed by immunohistochemistry tests. An intensity of 3+ EGFR reactivity in the cytoplasm (and/or membrane) of tumor cells was defined as overexpression of EGFR-C. The cutoff percentage of immunoreactive tumor cells for EGFR-N overexpression was 50%. Expression levels of EGFR-C and EGFR-N were further analyzed by clinicopathological features for 5-year survival disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). The results revealed that 20.9 and 23.3% of the cohort had high EGFR-N and EGFR-C expression, respectively. EGFR-N overexpression was significantly associated with advanced pre-treatment tumor stage (T3 and 4; P=0.017) and post-treatment tumor stage (T3 and 4; P<0.001). In univariate analysis, EGFR-N overexpression was significantly associated with poorer DSS (P=0.0005), MeFS (P=0.0182), and LRFS (P=0.0014). Furthermore, it remained an independent prognosticator of worse DSS [P=0.007, hazard ratio (HR)=2.755] and LRFS (P=0.0164, HR=3.026) in multivariate analysis. Overexpression of EGFR-N, and not EGFR-C, may help identify rectal cancer patients who have an increased risk of local recurrence and poor survival following neoadjuvant CCRT.

Preprogramming therapeutic response of PI3K/mTOR dual inhibitor via the regulation of EHMT2 and p27 in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, which is characterized by its high invasiveness, rapid progression, and profound resistance to therapy. Gemcitabine is the first-line treatment option for pancreatic cancer patients, but the overall survival is quite low. Therefore, it is an urgent issue to identify new molecules for improved therapies, with better efficacy and less toxicity. Our previous data indicated that Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) functions as a therapeutic target to override GEM resistance and promote metastasis in the treatment of pancreatic cancer. Here, we screened a small-molecule library of 143 protein kinase inhibitors, to verify cytotoxicity of different inhibitors in EHMT2-depleted cells. We determined that the EHMT2 plays a promising modulating role for targeted PI3K/mTOR inhibition. Our data revealed that EHMT2 down-regulates p27 expression, and this contributes to tumor growth. The depletion of EHMT2, ectopic expression of methyltransferase-dead EHMT2, or treatment with an EHMT2 inhibitor decreases H3K9 methylation of p27 promoter and induces G1 arrest in PANC-1 pancreatic cancer cells. Consistent with these findings, in vivo tumor xenograft models, primary tumors, and the Oncomine database utilizing bioinformatics approaches, also show a negative correlation between EHMT2 and p27. We further demonstrated that low EHMT2 elevated BEZ235 sensitivity through up-regulation of p27 in PDAC cells; high levels of SKP2 decrease BEZ235 responsiveness in PDAC cells. Altogether, our results suggest the EHMT2-p27 axis as a potential marker to modulate cell response to dual PI3K/mTOR inhibition, which might provide a strategy in personalized therapeutics for PDAC patients.

High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer.

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed. Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P=0.003). Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy.

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

An efficient reversible privacy-preserving data mining technology over data streams.

With the popularity of smart handheld devices and the emergence of cloud computing, users and companies can save various data, which may contain private data, to the cloud. Topics relating to data security have therefore received much attention. This study focuses on data stream environments and uses the concept of a sliding window to design a reversible privacy-preserving technology to process continuous data in real time, known as a continuous reversible privacy-preserving (CRP) algorithm. Data with CRP algorithm protection can be accurately recovered through a data recovery process. In addition, by using an embedded watermark, the integrity of the data can be verified. The results from the experiments show that, compared to existing algorithms, CRP is better at preserving knowledge and is more effective in terms of reducing information loss and privacy disclosure risk. In addition, it takes far less time for CRP to process continuous data than existing algorithms. As a result, CRP is confirmed as suitable for data stream environments and fulfills the requirements of being lightweight and energy-efficient for smart handheld devices.

Andrographolide inhibits proliferation of human lung cancer cells and the related mechanisms.

This study is to determine effect of Andrographolide (AD) on the growth of the non-small cell lung cancer cell line H3255. Expression of vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1), and the activity of protein kinase C (PKC) were also detected. The H3255 cells were treated with 1.0, 2.5, or 5.0 µM AD for 24 h. MTT assay was performed to examine cell viability. Levels of VEGF and TGF-ß1 were detected by ELISA. The ATPase activity and PKC activity were tested. AD treatments decreased cell viability via a concentration-dependent manner, leading to decreases in the Na(+)-K(+)-ATPase activities (P < 0.05). AD also increased levels of the DNA fragmentation and releasing of lactate dehydrogenase. AD also reduced VEGF and TGF-ß1 levels, and inhibited protein kinase C activities in H3255 cells (P < 0.05). AD inhibits proliferation of lung cancer cells via a concentration-dependent manner by a mechanism related to reducing levels of VEGF and TGF-ß1. Thus, AD might be a potent anti-lung cancer agent.

Andrographolide inhibits the activation of NF-κB and MMP-9 activity in H3255 lung cancer cells.

This study aimed to determine the effect of andrographolide (AD) on the growth of H3255 lung cancer cells and its possible impact on the expression and activity of the matrix metalloproteinase (MMP)-9 protein. H3255 cells were cultured in vitro, and treated with AD (1, 5 or 10 µM) for 24, 48 or 72 h. Cell proliferation was detected using an MTT assay and the expression of MMP-9 mRNA was measured using a reverse transcription-polymerase chain reaction (RT-PCR). The activity of MMP-9 was assessed by gelatin zymography, while the nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit and the phosphorylation of IκB were determined by western blotting. AD inhibited the proliferation of the H3255 cells in a concentration- and time-dependent manner, in addition to downregulating the expression of MMP-9 mRNA and the activity of MMP-9. Moreover, AD significantly inhibited the nuclear translocation of the NF-κB p65 subunit and suppressed IκB phosphorylation. The significant inhibition of H3255 cell proliferation by AD may have been correlated with the reduction in MMP-9 expression and activity through the inhibition of the phosphorylation of IκB and the translocation of NF-κB. The results suggest that AD is a promising drug candidate for the treatment of the migration and invasion of malignant tumors.

Surgical treatment of a giant cystic tumor of the atrioventricular nodal region.

Cystic tumor of the atrioventricular nodal region is a rare cardiac primary tumor that can cause heart blockage and sudden death. Antemortem diagnosis and successful excision of the atrioventricular nodal region are extremely rare. A 41-year-old woman who presented with dyspnea and palpitations is reported. Electrocardiography revealed third-degree atrioventricular block. Echocardiography showed a right atrial cystic mass attached to the interatrial septum. The patient underwent surgical excision of the mass. Histopathological findings were of a cystic tumor of the atrioventricular nodal region. Placement of a permanent pacemaker was required for complete heart blockage. A two-year follow-up has revealed no sign of recurrence. This is the first case to be reported in China.