The role of imprinting genes' loss of imprints in cancers and their clinical implications.

Genomic imprinting plays an important role in the growth and development of mammals. When the original imprint status of these genes is lost, known as loss of imprinting (LOI), it may affect growth, neurocognitive development, metabolism, and even tumor susceptibility. The LOI of imprint genes has gradually been found not only as an early event in tumorigenesis, but also to be involved in progression. More than 120 imprinted genes had been identified in humans. In this review, we summarized the most studied LOI of two gene clusters and 13 single genes in cancers. We focused on the roles they played, that is, as growth suppressors and anti-apoptosis agents, sustaining proliferative signaling or inducing angiogenesis; the molecular pathways they regulated; and especially their clinical significance. It is notable that 12 combined forms of multi-genes' LOI, 3 of which have already been used as diagnostic models, achieved good sensitivity, specificity, and accuracy. In addition, the methods used for LOI detection in existing research are classified into detection of biallelic expression (BAE), differentially methylated regions (DMRs), methylation, and single-nucleotide polymorphisms (SNPs). These all indicated that the detection of imprinting genes' LOI has potential clinical significance in cancer diagnosis, treatment, and prognosis.

Metabolomics Analysis and Diagnosis of Lung Cancer: Insights from Diverse Sample Types.

Lung cancer is a highly fatal disease that poses a significant global health burden. The absence of characteristic clinical symptoms frequently results in the diagnosis of most patients at advanced stages of lung cancer. Although low-dose computed tomography (LDCT) screening has become increasingly prevalent in clinical practice, its high rate of false positives continues to present a significant challenge. In addition to LDCT screening, tumor biomarker detection represents a critical approach for early diagnosis of lung cancer; unfortunately, no tumor marker with optimal sensitivity and specificity is currently available. Metabolomics has recently emerged as a promising field for developing novel tumor biomarkers. In this paper, we introduce metabolic pathways, instrument platforms, and a wide variety of sample types for lung cancer metabolomics. Specifically, we explore the strengths, limitations, and distinguishing features of various sample types employed in lung cancer metabolomics research. Additionally, we present the latest advances in lung cancer metabolomics research that utilize diverse sample types. We summarize and enumerate research studies that have investigated lung cancer metabolomics using different metabolomic sample types. Finally, we provide a perspective on the future of metabolomics research in lung cancer. Our discussion of the potential of metabolomics in developing new tumor biomarkers may inspire further study and innovation in this dynamic field.

Comprehensive Analysis of the COVID-19: Based on the Social-Related Indexes From NUMBEO.

Background: The COVID-19 has been spreading globally since 2019 and causes serious damage to the whole society. A macro perspective study to explore the changes of some social-related indexes of different countries is meaningful. Methods: We collected nine social-related indexes and the score of COVID-safety-assessment. Data analysis is carried out using three time series models. In particular, a prediction-correction procedure was employed to explore the impact of the pandemic on the indexes of developed and developing countries. Results: It shows that COVID-19 epidemic has an impact on the life of residents in various aspects, specifically in quality of life, purchasing power, and safety. Cluster analysis and bivariate statistical analysis further indicate that indexes affected by the pandemic in developed and developing countries are different. Conclusion: This pandemic has altered the lives of residents in many ways. Our further research shows that the impacts of social-related indexes in developed and developing countries are different, which is bounded up with their epidemic severity and control measures. On the other hand, the climate is crucial for the control of COVID-19. Consequently, exploring the changes of social-related indexes is significative, and it is conducive to provide targeted governance strategies for various countries. Our article will contribute to countries with different levels of development pay more attention to social changes and take timely and effective measures to adjust social changes while trying to control this pandemic.

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache.

Background: Migraineurs often exhibited abnormalities in cognition, emotion, and resting-state functional connectivity (rsFC), whereas patients with tension-type headache (TTH) rarely exhibited these abnormalities. The aim of this study is to explore whether rsFC alterations in brain regions related to cognition and emotion could be used to distinguish patients with migraine from patients with TTH. Methods: In this study, Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rsFC analyses were used to assess the cognition, anxiety, and depression of 24 healthy controls (HCs), 24 migraineurs, and 24 patients with TTH. Due to their important roles in neuropsychological functions, the bilateral amygdala and hippocampus were chosen as seed regions for rsFC analyses. We further assessed the accuracy of the potential rsFC alterations for distinguishing migraineurs from non-migraineurs (including HCs and patients with TTH) by the receiver operating characteristic (ROC) analysis. Associations between headache characteristics and rsFC features were calculated using a multi-linear regression model. This clinical trial protocol has been registered in the Chinese Clinical Trial Registry (registry number: ChiCTR1900024307, Registered: 5 July 2019-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=40817). Results: Migraineurs showed lower MoCA scores (p = 0.010) and higher SAS scores (p = 0.017) than HCs. Migraineurs also showed decreased rsFC in the bilateral calcarine/cuneus, lingual gyrus (seed: left amygdala), and bilateral calcarine/cuneus (seed: left hippocampus) in comparison to HCs and patients with TTH. These rsFC features demonstrated significant distinguishing capabilities and got a sensitivity of 82.6% and specificity of 81.8% with an area under the curve (AUC) of 0.868. rsFC alterations showed a significant correlation with headache frequency in migraineurs (p = 0.001, Pc = 0.020). Conclusion: The rsFC of amygdala and hippocampus with occipital lobe can be used to distinguish patients with migraine from patients with TTH. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?proj=40817], identifier [ChiCTR1900024307].

Dysregulated lncRNA and mRNA may promote the progression of ischemic stroke via immune and inflammatory pathways: results from RNA sequencing and bioinformatics analysis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are widely involved in gene transcription regulation and which act as epigenetic modifiers in many diseases. OBJECTIVE: To determine whether lncRNAs are involved in ischemic stroke (IS), we analyzed the expression profile of lncRNAs and mRNAs in IS. METHODS: RNA sequencing was performed on the blood of three pairs of IS patients and healthy controls. Differential expression analysis was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). Based on the co-expression relationships between lncRNA and mRNA, a series of bioinformatics analysis including GO and KEGG enrichment analysis and PPI analysis, were conducted to predict the function of lncRNA. RESULTS: RNA sequencing produced a total of 5 DElncRNAs and 144 DEmRNAs. Influenza A pathway and Herpes simplex infection pathway were the most significant pathways. EP300 and NFKB1 were the most important target proteins, and Human leucocyte antigen (HLA) family were the key genes in IS. CONCLUSIONS: Analysis of this study revealed that dysregulated lncRNAs in IS may lead to IS by affecting the immune and inflammation system.

Viral infection among children under the age of 5 with diarrhea in Shenyang from 2018 to 2020: A hospital-based study.

Diarrhea is one of the leading causes of death among children, especially in the age under 5, but few studies are available on viral diarrhea in Shenyang. To understand the infection status and the relevant epidemiological characteristics of viral diarrhea and to fill gaps of the distribution of viruses across Shenyang in children under the age of 5 with diarrhea, from 2018 to 2020, stool specimens of children with diarrhea aged 0-59 months and surveillance data were collected in Sentinel Hospital of Shenyang. Specimens were then tested to determine the type of viruses, the seasonal and spatial patterns for major viruses were determined. Viruses were identified in 47.9% of the 897 samples from children with diarrhea. The main viruses of stool samples were rotavirus (16.9%, predominant type G9P[8]), calicivirus (14.7%), adenovirus (11.8%), and astrovirus (4.5%). Viral infections were mainly detected in the age of 0-12 months. In the area of Shenyang, Huanggu had the most cases (198, 22.1%), followed by Dadong (137, 15.3%) and Hunnan (135, 15.1%). The positive rate of viruses varied among patients of different ages, seasons, and regions. Public health entities and the government should develop corresponding measures for different age groups, seasons, and regions.

WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects-a narrative review.

Background and Objective: WW domain binding protein 2 (WBP2), considered an emerging breast cancer gene, functions as a binding partner for WW domain proteins. The WBP2 gene is involved in mediating the malignant development and clinical drug resistance of breast cancer, but its potential mechanism remains unclear. Therefore, it is necessary to elucidate the mechanism of WBP2 in breast cancer, which will help to provide new methods for clinical diagnosis and treatment of breast cancer. Methods: The PubMed database was searched using the terms "WW Domain Binding Protein 2" or "WBP2", "breast cancer" or "breast neoplasms" or "human cancer" from January 1997 through August 2022. Through the screening and evaluation of titles and abstracts, about 120 English articles were included in this study. Key Content and Findings: By describing the multiple regulatory functions of WBP2 at the transcriptional, post-transcriptional, and post-translational levels, and summarizing how WBP2 as a key node crosstalks multiple signaling pathways, we reveal the ability of WBP2 to promote breast cancer malignant progression. In different subtypes of breast cancer, the mechanism of WBP2-mediated drug resistance is related to estrogen receptor and epidermal growth factor receptor (EGFR) 2 status, and hormones may be an essential factor in WBP2-mediated drug resistance. In addition, we discuss the application prospects of WBP2 in targeted therapy and immunotherapy and propose therapeutic strategies to overcome drug resistance in breast cancer by jointly targeting WBP2 and its related molecules. This provides a theoretical basis for the innovation of breast cancer targeted drugs. Conclusions: WBP2 is a promising target for breast cancer therapy. Nuclear WBP2, as the main functional form of WBP2 after its activation, is a meaningful indicator for the diagnosis and prediction of breast cancer progression.

A survey of mental health status of obstetric nurses during the novel coronavirus pneumonia pandemic.

ABSTRACT: To investigate the mental health status of obstetric nurses and its influencing factors during the novel coronavirus epidemic period, so as to provide theoretical reference for hospital decision-makers and managers.From February 25 to March 20, 2020, we conducted a cross-sectional survey through online questionnaire, and selected obstetric nurses from Jilin and Heilongjiang Provinces as the research objects by convenience sampling.Three hundred eighteen valid questionnaires were collected; the results of Symptom Checklist 90 showed that the scores of "obsessive-compulsive", "depression", "anxiety", "hostility", "phobia", and "psychosis" were higher than the Chinese norm (P < .01). There were 107 people whose total score of Symptom Checklist 90 was more than 160, and 83 people whose number of positive items was more than 43. Logistic regression results showed that married, temporary employment, lack of support and communication from family and relatives, onerous task, and unbearable responsibility were independent risk factors for mental disorder.There is a great psychological burden for obstetric nurses during the epidemic period. Decision makers should focus on necessary psychological intervention for those that are married, temporarily employed, and those lacking family supports including communication. At the same time, managers should distribute tasks reasonably to avoid psychological burdens caused by overwork.

E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.

Female breast cancer has become the most commonly occurring cancer worldwide. Although it has a good prognosis under early diagnosis and appropriate treatment, breast cancer metastasis drastically causes mortality. The process of metastasis, which includes cell epithelial-mesenchymal transition, invasion, migration, and colonization, is a multistep cascade of molecular events directed by gene mutations and altered protein expressions. Ubiquitin modification of proteins plays a common role in most of the biological processes. E3 ubiquitin ligase, the key regulator of protein ubiquitination, determines the fate of ubiquitinated proteins. E3 ubiquitin ligases target a broad spectrum of substrates. The aberrant functions of many E3 ubiquitin ligases can affect the biological behavior of cancer cells, including breast cancer metastasis. In this review, we provide an overview of these ligases, summarize the metastatic processes in which E3s are involved, and comprehensively describe the roles of E3 ubiquitin ligases. Furthermore, we classified E3 ubiquitin ligases based on their structure and analyzed them with the survival of breast cancer patients. Finally, we consider how our knowledge can be used for E3s' potency in the therapeutic intervention or prognostic assessment of metastatic breast cancer.

Identification of a lncRNA/circRNA-miRNA-mRNA network to explore the effects of ricin toxin-induced inflammation in RAW264.7 cells.

Ricin toxin (RT) is a ribosome-inactivating protein derived from the beans of the castor oil plant. Our previous studies have reported that RT can induce the production of inflammatory cytokines and cause inflammatory injury in RAW264.7 cells. In order to explore the various biological processes that long noncoding RNA (lncRNA), circular RNA (circRNA) and micro RNA (miRNA) as endogenous non-coding RNAs (ceRNAs) may participate in the pro-inflammatory mechanism, RT (20 ng/mL) treated and normal RAW264.7 cells were firstly sequenced by RNA-seq. By comparing the differentially expressed genes, we obtained 10 hub genes and enriched the inflammatory-related signaling pathways. Based on our results, we concluded a lncRNA/circRNA-miRNA-mRNA network. Finally, we verified the key genes and pathways by qRT-PCR, WB and ELISA. From the experiment results, an opening MAPK signaling pathway in TNF signaling pathway via TNFR2 was found involved in RT-induced inflammation. This work provides a reference for searching for ceRNA targets or therapeutic drugs in RT-induced inflammatory injury in the future.

Establishment of Serum TSH Reference Intervals by an Indirect Method for Healthy Population in Southwest China.

BACKGROUND: Serum thyroid stimulating hormone (TSH) detection is of great clinical significance in monitoring thyroid function. The aim of the present study was to establish reference intervals (RIs) for serum TSH in healthy Han population in Southwest China using data from routine health check-up individuals. METHODS: Healthy subjects (n = 7,116) were enrolled from January 2019 to September 2020. Serum TSH values were determined in the Beckman Coulter UniCel™ DxI 800 Access® immunoassay system. Outliers were identified and removed using Dixon's interactive principle. The 95th percentile range was calculated as RIs for serum TSH. All the statistical analyses were run on R statistical software version 4.0.3. RESULTS: A total of 6,668 (1,324 female and 5,344 male) suitable individuals were included in this study. Serum TSH results showed a non-Gaussian distribution by Kolmogorov-Smirnov test. According to Mann-Whitney U analysis, the serum TSH values for the female group differ from the male group's (p < 0.05). Besides, Spearman's rank correlation test disclosed that no obvious correlation was observed between serum TSH levels and age (r = -0.0039, p > 0.05). Accordingly, the RIs for serum TSH in Southwest China Han population were 0.64 (95% CI: 0.62 to 0.65) to 4.05 (95% CI: 4.02 to 4.09) mIU/L in male and 0.72 (95% CI: 0.67 to 0.77) to 5.66 (95% CI: 5.58 to 5.75) mIU/L in female, respectively. CONCLUSIONS: In this study, the laboratory specific RIs for serum TSH were successfully established by indirect method using the data from health check-up population. It implies that the indirect method is an easy and lowcost pathway for each laboratory to establish its own RIs.

Web tools to perform long non-coding RNAs analysis in oncology research.

Accumulated evidence suggests that the widely expressed long-non-coding RNAs (lncRNAs) are involved in biogenesis. Some aberrant lncRNAs are closely related to pathological changes, for instance, in cancer. Both in tumorigenesis and cancer progression, depending on the interplay with cellular molecules, lncRNAs can modulate transcriptional interference, chromatin remodeling, post-translational regulation and protein modification, and further interfere with signaling pathways. Aiming to the diagnosis/ prognosis markers or potential therapeutical targets, it is important to figure out the specific mechanism and the tissue-specific expressing patterns of lncRNAs. Generally, the bioinformatics analysis is the first step. More and more in silico databases are increasing. But the existing integrative online platforms' functions are not only having their unique features but also share some common features, which may lead to a waste of time for researchers. Here, we reviewed these web tools according to the functions. For each database, we clarified the data source, analysis method and the evidence that the analysis result is derived from. This review also illustrated examples in practical use for a specific lncRNA by these web tools. It will provide convenience for researchers to quickly choose the appropriate bioinformatics web tools in oncology studies.

Epidemiological study on severe acute respiratory syndrome coronavirus 2 virus transmission network in northeast China.

ABSTRACT: In this study, corona virus disease 2019 (COVID-19) transmission networks were built to analyze the epidemic situation of COVID-19 in Liaoning and Jilin provinces in early 2020. We explore the characteristics of the spread of COVID-19, and put forward effective recommendations for epidemic prevention and control. We collected demographic characteristics, exposure history, and course of action of COVID-19 cases. We described the demographic and case characteristics of these cases to show the basic characteristics of COVID-19 cases in both provinces. Combined with the spatial analysis of confirmed cases, the distribution law of the number of confirmed cases in different regions was analyzed. We exhibit the relationship among COVID-19 cases with a transmission network. The transmission characteristics of COVID-19 were analyzed through the transmission network. Mainly cases in Liaoning and Jilin provinces were imported cases from other provinces and the vast majority of these cases were related to Hubei province. The number of confirmed cases in different regions was positively correlated with their GDP and population. The main clinical symptoms of the cases were fever. Judge from the transmission network relationship between the 2 provinces, the transmission chain in Liaoning province contains fewer cases than that in Jilin province. The main transmission routes of the local cases in the 2 provinces were the family members, and the infection of the imported cases were mainly occurred in public places. It was estimated that the unidentified asymptomatic infected cases in the 2 provinces account for approximately 7.3% of the total number of infected cases. The length of the transmission chain suggests that the spread of COVID-19 can be effectively controlled with effective prevention measures.

Effect of temperature and its interaction with other meteorological factors on bacillary dysentery in Jilin Province, China.

Bacterial dysentery (BD) brings a major disease burden to developing countries. Exploring the influence of temperature and its interaction with other meteorological factors on BD is significant for the prevention and early warning of BD in the context of climate change. Daily BD cases and meteorological data from 2008 to 2018 were collected in all nine prefecture-level cities in Jilin Province. A one-stage province-level model and a two-stage city-specific multivariate meta-pooled level distributed lag non-linear model were established to explore the correlation between temperature and BD, then the weather-stratified generalised additive model was used to test the interaction. During the study period, a total of 26 971 cases of BD were developed. The one-stage and two-stage cumulative dose-response 'J' curves overlapped, and results showed a positive correlation between temperature and BD with a 1-6 days lag effect. Age group ⩾5 years was found to be more sensitive to the effects. Moreover, there was a significant interaction between temperature, humidity and precipitation (P = 0.004, 0.002, respectively) on BD under high temperature (>0 °C), reminding residents and policymakers to pay attention to the prevention of BD in situations with both high temperature and humidity, high temperature and precipitation during the temperate monsoon climate.

Causal associations of waist circumference and waist-to-hip ratio with type II diabetes mellitus: new evidence from Mendelian randomization.

Type II diabetes mellitus (T2DM) is a metabolic disease with high incidence, which has seriously affected human life and health. The associations among waist circumference (WC), waist-to-hip ratio (WHR), and T2DM were discovered in observational studies. However, the causality of these associations still remains unknown. The present study aims to apply two-sample Mendelian randomization (TSMR) using genetic variants as instrumental variables (IVs) to evaluate the causality among WC, WHR, and T2DM. The participants were from three independent studies in genome-wide association studies (GWAS) datasets, which included 127,997 Europeans for WC, 73,137 Europeans for WHR and 659,316 Europeans for T2DM. Furthermore, 16 were associated WC SNPs and eight were associated WHR SNPs as instrument variables were selected for TSMR using P < 5 × 10-8 standard. The pooled odd ratios (ORs) for the assessment of higher WC and WHR on the risk of T2DM for these SNPs were calculated using inverse variance weighted (IVW) method, and validated through extensively complementary analyses. The OR for T2DM per SD (cm) higher WC was 2.623 (95% CI 2.286-3.010, P = 5.000E-43), and the OR for T2DM per SD (cm) higher WHR was 1.751 (95% CI 1.122-2.733, P = 0.014). Consistent results for other methods were obtained. Furthermore, the range of OR fluctuation between WC and T2DM was from 2.623 to 2.986, while that between WHR and T2DM was from 0.990 to 2.931. Overall, these present results provide genetic support that suggests that the use of TSMR, and higher WC and WHR increased the T2DM risk among the European population.

A narrative review of research progress on FoxM1 in breast cancer carcinogenesis and therapeutics.

OBJECTIVE: The purpose of this review is to clarify the potential roles of forkhead box transcription factor M1 (FoxM1) in the occurrence and progression of breast cancer, as well as the predictive value of FoxM1 as a prognostic biomarker and potential therapeutic target for breast cancer. BACKGROUND: Breast cancer, well-known as a molecularly heterogeneous cancer, is still one of the most frequently diagnosed malignant tumors among females worldwide. Tumor recurrence and metastasis are the central causes of high mortality in breast cancer patients. Many factors contribute to the occurrence and progression of breast cancer, including FoxM1. FoxM1, widely regarded as a classic proliferation-related transcription factor, plays pivotal roles in the occurrence, proliferation, invasion, migration, drug resistance, and epithelial-mesenchymal transition (EMT) processes of multiple human tumors including breast cancer. METHODS: The PubMed database was searched for articles published in English from February 2008 to May 2021 using related keywords such as "forkhead box transcription factor M1", "human breast cancer", "FoxM1", and "human tumor". About 90 research papers and reports written in English were identified, most of which were published after 2015. These papers mainly concentrated on the functions of FoxM1 in the occurrence, development, drug resistance, and treatment of human breast cancer. CONCLUSIONS: Considering that the abnormal expression of FoxM1 plays a significant role in the proliferation, invasion, metastasis, and chemotherapy drug resistance of breast cancer, and its overexpression is closely correlated with the unfavorable clinicopathological characteristics of breast tumor patients, it is considerably important to comprehend the regulatory mechanism of FoxM1 in breast cancer. This will provide strong evidence for FoxM1 as a potential biomarker for the targeted treatment and prognostic evaluation of breast cancer patients.

Silencing microRNA-181a-5p suppresses malignant behavior of lacrimal adenoid cystic carcinoma cells by upregulating large tumor suppressor 2.

To uncover the effect of miR-181a-5p regulating large tumor suppressor 2 (LATS2) in biologic processes of adenoid cystic carcinoma (ACC) cells, miR-181a-5p and LATS2 expression in lacrimal ACC (LACC) tissues were assessed. The ACC cell lines were respectively treated with altered miR-181a-5p or LATS2 to determine the biologic functions in ACC cells. Binding ability of miR-181a-5p and LATS2 was confirmed. Tumor growth in vivo was assessed as well. MiR-181a-5p was upregulated while LATS2 was downregulated in LACC tissues. Reduced miR-181a-5p restrained malignant phenotype of ACC cells and decelerated xenograft growth. Conversely, LATS2 reduction had opposite effects compared to miR-181a-5p knockdown on ACC cells. Furthermore, downregulated LATS2 could abolish the alterations in ACC cells induced by miR-181a-5p silencing. MiR-181a-5p inhibition upregulated LATS2 to suppress malignant behavior of ACC cells in vivo and in vitro.

Diagnosis of lacrimal punctum lesions using optical coherence tomography: a preliminary study.

AIM: To study the imaging characteristics of lacrimal punctum lesion with optical coherence tomography (OCT), and provide imaging basis for the diagnosis and treatment of lacrimal punctum diseases. METHODS: A total of 25 patients (28 eyes) with epiphora and lacrimal puncta lesions were enrolled. Lacrimal puncta lesions included: punctum membrane obstruction in 7 cases (9 eyes), punctum agenesis in 1 case (1 eye), a mass protruded from the punctum in 1 case (1 eye), slit puncta in 1 case (1 eye), peri-puncta mass in 2 cases (2 eyes), chronic dacryocystitis in 4 cases (4 eyes), and primary puncta stenosis in 9 cases (10 eyes; 3 eyes mild, 4 eyes moderate and 3 eyes severe). All patients were examined by slit lamp microscopy and OCT to observe the morphological characteristics of abnormal punctum. RESULTS: Two types of complete membrane obstruction and incomplete membrane obstruction of puncta were observed in OCT images of 7 patients. No lacrimal punctum and lacrimal canalicular cavity were found in 1 case with punctum agenesis. OCT images showed that a narrow lumen remained in the lacrimal puncta in 1 patient with a mass protruded from the punctum. OCT of punctum in a patient with slit punctum after stent placement showed stent and abnormal lacrimal structure. No abnormal intraluminal structure was found in 2 cases of peri-puncta mass after OCT scan, and the lacunar space was narrower than that of the contralateral eye. OCT of puncta in 4 patients with chronic dacryocystitis showed that pus floated in tear with lump-like medium-low reflex. In 9 patients with primary lacrimal puncta stenosis, OCT image could clearly show the changes of puncta lumen in different degrees and shapes. CONCLUSION: OCT is feasible for the examination of pathological punctum, and can provide imaging basis for the diagnosis and treatment of punctum disease.

A systematic analysis reveals gene expression alteration of serum deprivation response (SDPR) gene is significantly associated with the survival of patients with cancer.

Serum deprivation response (SDPR) gene has been recently characterized as a gene signature marker or serving a tumor suppressor role in specific types of cancer. However, gene expression alterations of SDPR in various types of cancer and their relevance to clinical outcomes remain unclear. In the present study, SDPR expression was profiled using the Oncomine database, and SDPR downregulation was indicated in most types of cancer. In agreement with previously reported breast cancer cases, downregulation of SDPR was indicated to be significantly associated with poor survival in patients with lung cancer, glioma and sarcoma. To clarify why SDPR expression was altered in these types of cancer, both DNA methylation patterns and potential transcriptional factors of SDPR were analyzed. Altered DNA methylation levels of SDPR were found in 17/18 cancer types using MethHC. To the best of our knowledge, the present study for the first time, identified the CpG site (cg10082589) as one of the best survival methylation markers for lung adenocarcinoma, and the CpG site (cg07488576) for sarcoma using Methsurv. In addition, GATA binding protein 2 was identified as a potential transcription factor for SDPR, by integrating and analyzing both the co­expressed genes and the potential transcription factor binding sites of SDPR. In the present study, the systematic analysis of SDPR provided insight for the underlying molecular mechanisms in cancer progression, revealing novel perspectives for the clinical prognostic evaluation of lung adenocarcinoma and sarcoma.

A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor.

Retinoblastoma protein (RB) plays critical roles in tumor suppression and is degraded through the proteasomal pathway. However, E3 ubiquitin ligases responsible for proteasome-mediated degradation of RB are largely unknown. Here we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes RB degradation. NRBE3 contains an LXCXE motif and bound RB in vitro. NRBE3 interacted with RB in cells when proteasome activity was inhibited. NRBE3 promoted RB ubiquitination and degradation via the ubiquitin-proteasome pathway. Importantly, purified NRBE3 ubiquitinated recombinant RB in vitro, and a U-box was identified as essential for its E3 activity. Surprisingly, NRBE3 was transcriptionally activated by E2F1/DP1. Consequently, NRBE3 affected the cell cycle by promoting G1/S transition. Moreover, NRBE3 was up-regulated in breast cancer tissues. Taken together, we identified NRBE3 as a novel ubiquitin E3 ligase for RB that might play a role as a potential oncoprotein in human cancers.