The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

FBXO38 mediates FGL1 ubiquitination and degradation to enhance cancer immunity and suppress inflammation.

Upregulation of FGL1 helps tumors escape from immune surveillance, and therapeutic antibodies targeting FGL1 have potential as another immune checkpoint inhibitor. However, the underlying mechanism of high FGL1 protein level in cancers is not well defined. Here, we report that FBXO38 interacts with and ubiquitylates FGL1 to negatively regulate its stability and to mediate cancer immune response. Depletion of FBXO38 markedly augments FGL1 abundance, not only suppressing CD8+ T cell infiltration and enhancing immune evasion of tumor but also increasing inflammation in mice. Importantly, we observe a negative correlation of FBXO38 with FGL1 and IL-6 in non-small cell lung cancer specimens. FGL1 and IL-6 levels positively correlate with TNM (tumor, lymph node, metastasis) stages, while FBXO38 and the infiltrating CD8+ T cells negatively correlate with TNM stages. Our study identifies a mechanism regulating FGL1 stability and a target to enhance the immunotherapy and suggests that the combination of anti-FGL1 and anti-IL-6 is a potential therapeutic strategy for cancer immunotherapy.

Association of gastrointestinal symptoms and skipping breakfast with anxiety and depressive symptoms in quarantined Chinese college students during the Shanghai 2022 lockdown: a cross sectional survey.

BACKGROUND: This study aimed to evaluate the prevalence of anxiety and depressive symptoms among quarantined college students at school in Shanghai 2022 lockdown during the COVID-19 pandemic and investigate the association of gastrointestinal discomfort related-factors and skipping breakfast with anxiety and depressive symptoms. METHODS: 384 quarantined college students in Shanghai China were recruited in this cross-sectional study from April 5th to May 29th, 2022. Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to assess anxiety and depressive symptoms, respectively. RESULTS: The prevalence of anxiety and depressive symptoms were 56.8% and 62.8%, respectively. Longer quarantine duration, higher education level, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were significantly associated with anxiety symptoms. Moreover, longer quarantine duration, being woman, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were markedly related to depressive symptoms. Notably, regularly physical exercising and taking positive attitude towards COVID-19 were negatively correlated with anxiety and depressive symptoms. CONCLUSIONS: More attention should be paid to anxiety and depressive symptoms of quarantined college students and universities should provide timely psychological monitoring and intervention services to mitigate the impact of negative emotions on students. Effectively relieving gastrointestinal symptoms, insisting on eat breakfast, regularly exercising, and taking a positive attitude towards to COVID-19 might contribute to preventing the anxiety and depressive symptoms for those college students experiencing a long-term quarantine.

Effect of umifenovir (arbidol) versus standard care on clinical outcome in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to spread quickly throughout the world, mainly due to the lack of effective drug therapies and vaccines. The effectiveness of the antiviral drug umifenovir needs to be further clarified. METHODS: This retrospective cohort study included 1254 patients who were diagnosed with COVID-19 between February 19 and April 5, 2020 in Hubei Maternity and Child Health Hospital. They were divided into umifenovir group (n = 760, 60.60%) and control group (n = 496) without using umifenovir. The primary endpoint was a composite of intubation or death in a time-to-event analysis. The clinical outcomes were compared between the two groups using multivariable Cox analysis with inverse probability weighting according to the propensity score. RESULTS: A total of 760 (60.60%) patients received umifenovir, and 496 patients did not do so. Of the enrolled patients, 1049 (83.65%) had mild or moderate COVID-19, and the remaining 205 had severe or critical COVID-19. The mortality rate in the umifenovir group was 2.76% (21/760) versus 2.02% (10/494) in the control group. In terms of treatment outcomes, the discharge status of the patients in the umifenovir group was no better than that in the control group after propensity score matching (n = 485 in each group). In addition, the respiratory rate, a severe condition, or critical condition of the disease were the three main risk factors affecting the endpoint of death (p = 0.0028, p = 0.0009 and p < 0.0001, respectively). CONCLUSION: This retrospective cohort study showed that oral administration of umifenovir alone did not improve outcomes for patients with COVID-19.

Highly absorbent bio-sponge based on carboxymethyl chitosan/poly-γ-glutamic acid/platelet-rich plasma for hemostasis and wound healing.

Stopping bleeding at an early stage and promoting wound healing are of great significance for efficient wound management. In this study, a carboxymethyl chitosan (CMCS)/poly-γ-glutamic acid (γ-PGA)/platelet-rich plasma (PRP) hydrogel (CP-PRP hydrogel) was firstly prepared by crosslinking of CMCS with γ-PGA and the enzymatic coagulation of PRP. Then, the CP-PRP hydrogel was freeze-dried and transformed into a sponge (CP-PRP sponge). A series of safety experiments with cells, blood, and tissues proved the biocompatibility of the CP-PRP sponge. Importantly, the CP-PRP sponge was able to adhere and condense red blood cells, which accelerated blood clotting. Therefore, the CP-PRP sponge showed an enhanced hemostasis effect compared to SURGIFLO® Hemostatic Matrix. Moreover, in vitro and in vivo experiments showed that the sponge was able to release epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Thus, in a mouse model of full-thickness skin defects, the wounds of the sponge-treated mice were significantly healed within two weeks. These results proved the transforming potential of the CP-PRP sponge as a novel bioactive wound dressing.

Normalized TSH strategy can improve the initial assessment of thyroid nodules.

BACKGROUND: Serum thyrotropin (TSH) has been recommended for the initial assessment of patients with thyroid nodules to exclude functional thyroid nodules (FTN). However, the sensitivity of TSH is very low. The increased level of thyroid peroxidase antibody (TPOAb) is considered to be one of the reasons. OBJECTIVE: To investigate whether normalized TSH (nTSH) can improve diagnostic efficiency by removing TPOAb interference in the first evaluation of thyroid nodules compared with traditional TSH strategy. METHODS: Thyroid nodules were retrospectively analysed in 90 patients with FTN and 1038 patients with non-functioning thyroid nodules (non-FTN). The regression coefficient (ß) of TPOAb affecting the TSH levels was assessed in patients with thyroid nodules, and then, the nTSH level was calculated based on the following formula: nTSH = TSH-ß*TPOAb. We used nTSH levels to initially evaluate the thyroid nodules instead of the traditional TSH values and finally compared the results of the two strategies. RESULTS: The sensitivity, specificity, accuracy, positive prediction rate (PPV) and negative prediction rate (NPV) of nTSH for accessing FTN were 50.00%, 87.70%, 84.67%, 26.01% and 95.29%, respectively, which were better than the values of 48.90%, 78.70%, 76.33%, 16.60% and 94.67% associated with TSH, respectively (p < 0.001). CONCLUSION: Serum TPOAb testing is recommended for the first assessment of thyroid nodules. Normalized TSH levels can improve assessment efficiency compared to traditional TSH assessment, increase the specificity and reduce an unnecessary 99mTc-TS test.

A Model Combining Testosterone, Androstenedione and Free Testosterone Index Improved the Diagnostic Efficiency of Polycystic Ovary Syndrome.

OBJECTIVE: Hyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic ovary syndrome (PCOS) and to evaluate and compare the value of androstenedione (Andro) and other hormone indicators in the diagnosis of patients with hyperandrogenic PCOS. METHODS: This study included 139 women diagnosed with hyperandrogenic PCOS according to the Rotterdam criteria and 74 healthy control women from Shanghai Tenth People's Hospital. The serum hormone levels of the patients and controls were measured using a chemiluminescence immunoassay and incorporated for further analysis. RESULTS: Total testosterone (TT), Andro, dehydroepiandrosterone sulfate (DHEAS), and free androgen index (FAI) were significantly higher in the PCOS group than the control group. Further, Andro, follicle-stimulating hormone (FSH), luteinizing hormone (LH), TT, FAI, and LH/FSH in the hyperandrostenedione group were higher than the normal Andro group. The Youden index was the highest for Andro (0.65), with 81.82% sensitivity and 83.16% specificity. Correlation analysis showed that FSH, LH, TT, FAI, insulin sensitivity index, and LH/FSH were positively correlated with Andro, while fasting blood glucose and 2-hour postprandial blood glucose were negatively correlated with Andro. CONCLUSIONS: The model using Andro, TT, and FAI may help to identifying women with undiagnosed PCOS. Serum Andro is a meaningful biomarker for hyperandrogenism in PCOS patients and may further aid disease diagnosis.

Sodium alginate hydrogel containing platelet-rich plasma for wound healing.

Recently, the healing of chronic wounds such as extensive burns has become a serious and intractable clinical problem. Avoiding wound infection and retaining an appropriate level of moisture around wounds are significant challenges in wound care. Herein, a dual-network hydrogel composed of sodium alginate (SA) and platelet-rich plasma (PRP) was designed to facilitate the wound healing. The preparation of hydrogel was achieved through a simple one-step thrombin activation process. The morphological characterization results revealed the three-dimensional network structure of the hydrogel. Then, certain levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were detected in phosphate buffer solution (PBS) cultured hydrogel, which led to the possibility of cell proliferation and vascular regeneration. When topically applied to the wound skin of rats, the hydrogel presented high wound closure effectiveness. In conclusion, this strategy provides a simple and feasible approach to overcoming the shortcomings of conventional wound dressings.

Employment Intention of Chinese Medical Students During the COVID-19 Epidemic: A Cross-Sectional Survey.

Context: In the process of combating the coronavirus disease 2019 (COVID-19) epidemic, medical personnel were at the forefront of the fight. As the future medical workforce, medical students often experienced firsthand how their seniors and teachers had to commit to working hard in combating the epidemic. Many were directly involved in the front line of the fight and that experience could easily have affected their intention to seek employment in a medically related career. Objective: The study intended to evaluate the impact of the COVID-19 pandemic on Chinese medical students' employment intentions and the factors associated with them to put forward relevant suggestions to provide a basis for medical education in the future. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place in many provinces and cities in China and was conducted in an online questionnaire. Participants: Participants were 1114 college students studying clinical medicine, college students studying nursing, and students interning during standardized resident training, medical interns. Outcome Measures: The participants completed a self-administered questionnaire, which investigated their psychological statuses related to anxiety and depression as well as COVID-19's impact on their intentions related to job searches, regarding their willingness to engage in clinical or basic research in epidemic-related specialties and epidemic-related work. Results: Compared to college students studying clinical medicine, the employment intentions of nursing students and medical interns were more vulnerable to the epidemic. Females and nursing students were more reluctant to choose clinical work, and the choice was associated with depression. Nursing college students and medical interns were significantly less willing to engage in infection medicine, respiratory medicine, and intensive care medicine (all P < .001). Medical students with a bachelor's degree and postgraduate degrees were significantly less willing to engage in infection medicine and respiratory medicine (all P < .001), but medical students from regions with stable epidemics were more willing to engage in intensive care medicine. Medical students with a bachelor's degree were significantly less likely to be involved in epidemiology-related work than undergraduate students, and students from severe epidemic regions were significantly less willing to work in isolation wards or to go to Wuhan as volunteers. Conclusions: Participants' psychological statuses related to anxiety and depression, genders, degrees, current educational statuses, and regions affected employment intentions during the epidemic.

The regulation role and diagnostic value of fibrinogen-like protein 1 revealed by pan-cancer analysis.

Although the role of fibrinogen-like protein 1 (FGL1) in tumorigenesis is well known, a pan-cancer analysis of FGL1 lacks. We used bioinformatics techniques to analyze cancer data from publicly available datasets from The Cancer Genome Atlas, UALCAN, TIMER, Gene Expression Profiling Interactive Analysis, cBioPortal, Search Tool for the Retrieval of Interacting Genes, and DAVID. FGL1 expression was significantly regulated in various common tumors than in normal tissues; it was increased in lung adenocarcinoma and decreased in colon adenocarcinoma. Cox regression analysis demonstrated that the upregulation of FGL1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in stomach adenocarcinoma, brain low-grade glioma, cervical squamous cell carcinoma, and endocervical adenocarcinoma. Decreased FGL1 methylation levels were observed in majority of tumor types. FGL1 expression was significantly associated with the levels of immune cell subtypes and immune checkpoint genes. Deep deletion was the most common genetic mutation in FGL1 that led to frame-shift mutations, which was closely associated with poor progression-free interval, disease-specific survival, and OS in patients with FGL1 mutations. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that FGL1-related genes participate in diverse pathways. Ubiquitin-mediated proteolysis is significantly correlated to the function of FGL1, which was identified for the first time in the present study. This pan-cancer study provides a deep understanding of the functions of FGL1 in progression of many tumors and demonstrates that FGL1 may be a potential biomarker for the diagnosis, prognosis, and immune infiltration in cancer.

Analyzing the influence of COVID-19 epidemic on the employment intention of resident physicians in China.

INTRODUCTION: To investigate the effects and influencing factors of the COVID-19 epidemic on the employment intention of resident physicians in China. METHODOLOGY: 409 questionnaires were statistically analyzed after removing the missing values. We used the Chi-Square test for single-factor analysis and logistic regression analysis for multivariate analysis. The questions include the residents' employment intention and their willingness to engage in epidemic-related subspecialties and participate in epidemic-related work. RESULTS: Residents of severe and high-risk epidemic regions had much lower employment intentions than those of stable epidemic regions (OR = 1.917, 95% CI: 1.024, 3.591, p = 0.042). The higher the Center for Epidemiologic Studies Depression Scale (CES-D) score, the more susceptible was the resident's employement intention (OR = 1.085, 95% CI: 1.044, 1.128, p < 0.001). Residents from severe and high-risk epidemic regions were more willing to participate in clinical work (OR = 4.263, 95% CI: 1.892, 9.604, p < 0.001), and the higher the CES-D score, the lower was the proportion of residents willing to choose clinical work (OR = 0.941, 95% CI: 0.893, 0.992, p = 0.023). Residents from severe epidemics and high-risk provinces were less willing to participate in respiratory medicine (χ2 = 5.070, p = 0.027) and critical care medicine (χ2 = 7.046, p = 0.011). Compared to residents with bachelor's degrees, residents with master's and doctoral degrees were less willing to participate in isolation wards (OR = 1.831, 95% CI: 1.122, 2.990, p = 0.016). Residents in epidemic-related current rotation departments were less willing to go to Wuhan as volunteers (OR = 2.197, 95% CI: 1.110, 4.347, p = 0.024). CONCLUSIONS: The COVID-19 outbreak had a negative impact on the job intentions of Chinese residents in general.

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma.

Liver cancer has high rates of morbidity and mortality, and its treatment is a global health challenge. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancer cases. B-lymphoma Mo-MLV insertion region 1 (BMI1) has been identified as a proto-oncogene, which contributes to the initiation and progression of many malignant tumors. BMI1 expression is upregulated in HCC, and it influences the occurrence and development of HCC by various mechanisms, such as the INK4a/ARF locus, NF-κB signaling pathway, and PTEN/PI3K/AKT signaling pathway. In addition, the expression of BMI1 is related to prognosis and recurrence of HCC. Hence, there is clear evidence that BMI1 is a novel and valid therapeutic target for HCC. Accordingly, the development of therapeutic strategies targeting BMI1 has been a focus of recent research, providing new directions for HCC treatment. This review summarizes the role of BMI1 in the occurrence and treatment of HCC, which will provide a basis for using BMI1 as a potential target for the development of therapeutic strategies for HCC.

Risk factors for recurrent positive results of the nucleic acid amplification test for COVID-19 patients: a retrospective study.

Positive retests of COVID-19 represent a public health concern because of the increased risk of transmission. This study explored whether factors other than the nucleic acid amplification test (NAAT) contribute to positive retest results. Patients with COVID-19 admitted to the Guanggu district of the Hubei Maternal and Child Health Hospital between February 17 and March 28, 2020, were retrospectively included. The patients were grouped into the negative (n = 133) and positive (n = 51) retest groups. The results showed that the proportion of patients presenting with cough was higher (P < 0.001) and the proportion of patients with dyspnea was lower (P = 0.018) in the positive than in the negative retest group. The positive retest group showed shorter durations between symptom onset and hospitalization (P < 0.001) and symptom onset and the first positive NAAT (P = 0.033). The positive retest group had higher basophil counts (P = 0.023) and direct bilirubin (P = 0.032) and chlorine concentrations (P = 0.023) but lower potassium concentrations (P = 0.001) than the negative retest group. Multivariable regression analysis showed that coughing (OR = 7.59, 95% CI 2.28-25.32, P = 0.001) and serum chloride concentrations (OR = 1.38, 95% CI 1.08-1.77, P = 0.010) were independently associated with a positive retest result. Coughing and serum chloride concentrations were independent risk factors for positive NAAT retest results. Patients with a hospital stay of < 2 weeks or a short incubation period should stay in isolation and be monitored to reduce transmission. These results could help identify patients who require closer surveillance.

Cytokines: Application in recurrence appraisal for differentiated thyroid carcinoma and their relation with radioiodine ablation.

The limitations in discriminating preablation disease-active status of differentiated thyroid carcinoma (DTC) still represent a major challenge to radioiodine dose management. Cytokines, the small protein signaling molecules that constitute the thyroid tumor microenvironment, play significant roles in the facilitation of intercellular communication and the control of tumorigenesis. Also, more attention should be paid to the molecular events within the innate and adaptive immune systems that occur after the organism being exposed to ionizing radiation. Therefore, we implemented a study of 260 patients with DTC in thyroid hormone withdrawal status who were treated with total thyroidectomy to explore the relationship between cytokines and recurrence/active disease status. Besides, we made a cross-sectional study to analyze pre- and post-ablation serum concentration of cytokines of 86 patients with DTC. There was a relationship between clinicohistopathological characteristics of patients with DTC and the presence of cytokines. It is noteworthy that patients with recurrence/active disease were at a higher serum interleukin-2 receptor (IL-2R) level than the disease-free patients (213.59 ± 75.43 pg/ml vs. 186.80 ± 77.40 pg/ml, P = 0.005). Positive correlation was observed between serum IL-2R and thyroglobulin (Tg) (P = 0.003). We also found significant changes in the cytokine profile after radioiodine ablation, including the decrease of tumor necrosis factor-α and IL-8 (P < 0.001, P < 0.001, respectively), and increase of IL-2R (P < 0.001). Thus, we suggest that serum IL-2R may assist in evaluating the disease status during the post-thyroidectomy follow-up and radioiodine therapy has an immunoregulatory effect on serum cytokines.

An 8 miRNA-Based Risk Score System for Predicting the Prognosis of Patients With Papillary Thyroid Cancer.

BACKGROUND: Dysregulation of microRNAs (miRNAs) in papillary thyroid cancer (PTC) might influence prognosis of PTC. This study is aimed to develop a risk score system for predicting prognosis of PTC. METHODS: The miRNA and gene expression profiles of PTC were obtained from The Cancer Genome Atlas database. PTC samples were randomly separated into training set (n = 248) and validation set (n = 248). The differentially expressed miRNAs (DE-miRNAs) in the training set were screened using limma package. The independent prognosis-associated DE-miRNAs were identified for building a risk score system. Risk score of PTC samples in the training set was calculated and samples were divided into high risk group and low risk group. Kaplan-Meier curves and receiver operating characteristic (ROC) curve were used to assess the accuracy of the risk score system in the training set, validation set and entire set. Finally, a miRNA-gene regulatory network was visualized by Cytoscape software, followed by enrichment analysis. RESULTS: Totally, 162 DE-miRNAs between tumor and control groups in the training set were identified. An 8 independent prognosis-associated DE-miRNAs, (including miR-1179, miR-133b, miR-3194, miR-3912, miR-548j, miR-6720, miR-6734, and miR-6843) based risk score system was developed. The area under ROC curve in the training set, validation set and entire set was all above 0.93. A miRNA-gene regulatory network involving the 8 DE-miRNAs were built and functional enrichment analysis suggested the genes in the network were significantly enriched into 13 pathways, including calcium signaling pathway and hedgehog signaling pathway. CONCLUSION: The risk score system developed this study might be used for predicting the prognosis of PTC. Besides, the 8 miRNAs might affect the prognosis of PTC via hedgehog signaling pathway and calcium signaling pathway.

Clinical implications of different specimen types for nucleic acid testing in two cases of COVID-19.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test is currently the gold standard for diagnosing coronavirus disease 2019 (COVID-19). This disease requires high-quality viral nucleic acid tests, and selecting the type of specimen from patients, who are at different disease stages, to use in the nucleic acid test is challenging. This article reports in detail the diagnosis and treatment process for two patients with confirmed COVID-19 and analyzes the results of the SARS-CoV-2 nucleic acid tests that were used for different types of specimens (sputum from deep cough, nasopharyngeal swab, and feces). The nucleic acid testing results of sputum from deep cough showed the best performance for positive detection. Our findings provide a reference for selecting the most suitable specimen for the clinical diagnosis of COVID-19 and improving the positive detection rate.

Weighted Gene Coexpression Network Analysis Reveals the Dynamic Transcriptome Regulation and Prognostic Biomarkers of Hepatocellular Carcinoma.

This study was aimed at revealing the dynamic regulation of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in hepatocellular carcinoma (HCC) and to identify HCC biomarkers capable of predicting prognosis. Differentially expressed mRNAs (DEmRNAs), lncRNAs, and miRNAs were acquired by comparing expression profiles of HCC with normal samples, using an expression data set from The Cancer Genome Atlas. Altered biological functions and pathways in HCC were analyzed by subjecting DEmRNAs to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene modules significantly associated with disease status were identified by weighted gene coexpression network analysis. An lncRNA-mRNA and an miRNA-mRNA coexpression network were constructed for genes in disease-related modules, followed by the identification of prognostic biomarkers using Kaplan-Meier survival analysis. Differential expression and association with the prognosis of 4 miRNAs were verified in independent data sets. A total of 1220 differentially expressed genes were identified between HCC and normal samples. Differentially expressed mRNAs were significantly enriched in functions and pathways related to "plasma membrane structure," "sensory perception," "metabolism," and "cell proliferation." Two disease-associated gene modules were identified. Among genes in lncRNA-mRNA and miRNA-mRNA coexpression networks, 9 DEmRNAs and 7 DEmiRNAs were identified to be potential prognostic biomarkers. MIMAT0000102, MIMAT0003882, and MIMAT0004677 were successfully validated in independent data sets. Our results may advance our understanding of molecular mechanisms underlying HCC. The biomarkers may contribute to diagnosis in future clinical practice.

The expression and clinical significance of secretory leukocyte proteinase inhibitor (SLPI) in mammary carcinoma using bioinformatics analysis.

BACKGROUND: Secretory leukocyte protease inhibitor (SPLI) was a secreted protein which belongs to a member of whey acidic protein four-disulfide core family. In breast cancer (BC) it may inhibit cell proliferation and promote cancer metastasis. In this study, a comprehensive bioinformatics analysis was performed to identify the expression and prognostic value of SLPI in breast cancer. METHODS: SLPI expression in breast cancer was analyzed in Oncomine online database, which was subsequently confirmed by quantitative PCR (qPCR) in 18 BC samples and western blotting in 26 BC samples. Breast cancer gene-expression miner v4.1 was used to access the expression level with clinicopathological parameters in breast cancer patients. The prognostic values of SLPI in breast cancer were evaluated using the PrognoScan database. RESULTS: Our results indicated that SLPI was downregulated in breast cancer than in normal tissues. SLPI expression was found to be negatively correlated with estrogen receptor (ER) and progesterone receptor (PR) status. SLPI expression level was decreased in negative basal-like status patients compared with positive basal-like status. Meanwhile, triple-negative breast cancer status positive correlated with SLPI. We confirmed a positive correlation between SLPI and interleukin 17 receptor B (IL17RB) express in breast cancer tissues via oncomine co-expression analysis. Ten proteins: Elastase, Granulin, Lipocalin, Defensin beta 103B, Defensin beta 103A, Tubulin, Heparin-binding EGF-like growth factor, Interleukin 6, Epidermal growth factor, Phospholipid scramblase 1 were determinate interactions with SLPI by STRING. CONCLUSION: SLPI could as a biomarker to predict the prognosis values of breast cancer. However, further comprehensive study and mining more evidence are needed to clarify our results.

A Pretreatment CT Model Predicts Survival Following Chemolipiodolization in Patients With Hepatocellular Carcinoma.

PURPOSE: To establish a computed tomography-based prognostic model for patients with hepatocellular carcinoma treated with transarterial chemoembolization. MATERIALS AND METHODS: Using prospectively collected data from 195 consecutive patients with hepatocellular carcinoma who underwent chemolipiodolization at the Eastern Hepatobiliary Surgery Hospital between 2013 and 2016, we established a prognostic model based on hepatocellular carcinoma enhancement patterns on computed tomography scans to predict the outcome of transarterial chemoembolization. Furthermore, a histopathology analysis was performed on 108 different patients undergoing resection between 2014 and 2016 to identify whether there was a correlation between enhancement pattern and microvessel density. RESULTS: The prognostic model classified hepatocellular carcinoma into 3 types: type I, which reached peak enhancement during the arterial phase and had a high mean microvessel density (101.5 vessels/0.74 mm2); type II, which reached peak enhancement during the portal venous or delayed phase and had an intermediate microvessel density (53.6 vessels/0.74 mm2); and type III, in which the tumor was insignificantly enhanced and had a low microvessel density (21.1 vessels/0.74 mm2). For type I, II, and III hepatocellular carcinoma, the post-transarterial chemoembolization 1-year tumor complete necrosis rates were 13.7%, 36.5%, and 0%, respectively (P < .001), and the 3-year overall survival rates were 14.1%, 38.6%, and 0%, respectively (P < .001). CONCLUSION: Our results indicate that hepatocellular carcinoma type is an independent predictor of complete necrosis and overall survival.

Prognostic implications of decreased microRNA-101-3p expression in patients with non-small cell lung cancer.

To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.