Myricetin mitigates motor disturbance and decreases neuronal ferroptosis in a rat model of Parkinson's disease.

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

The role of γδT lymphocytes in atherosclerosis.

Atherosclerosis poses a significant threat to human health, impacting overall well-being and imposing substantial financial burdens. Current treatment strategies mainly focus on managing low-density lipids (LDL) and optimizing liver functions. However, it's crucial to recognize that Atherosclerosis involves more than just lipid accumulation; it entails a complex interplay of immune responses. Research highlights the pivotal role of lipid-laden macrophages in the formation of atherosclerotic plaques. These macrophages attract lymphocytes like CD4 and CD8 to the inflamed site, potentially intensifying the inflammatory response. γδ T lymphocytes, with their diverse functions in innate and adaptive immune responses, pathogen defense, antigen presentation, and inflammation regulation, have been implicated in the early stages of Atherosclerosis. However, our understanding of the roles of γδ T cells in Atherosclerosis remains limited. This mini-review aims to shed light on the characteristics and functions of γδ T cells in Atherosclerosis. By gaining insights into the roles of γδ T cells, we may uncover a promising strategy to mitigate plaque buildup and dampen the inflammatory response, thereby opening new avenues for effectively managing this condition.

Increased PLAGL1 Gene Methylation in Cord Blood is Positively Correlated with Brain Injury in Chorioamniotic Preterm Infants.

The study aims to explore the epigenetic mechanisms of neurodevelopmental impairment accompanied in chorioamniotic preterm infants. Our study included 16 full-term infants and 69 preterm infants. The methylation status of the pleomorphic adenoma gene-like 1 (PLAGL1) gene in the cord blood was determined by pyrosequencing. Brain B-ultrasonography and magnetic resonance imaging (MRI) were performed to diagnose brain injury. The activity of candidate fragments of PLAGL1 and the effect of methylation on PLAGL1 activity were evaluated by double luciferase reporter assay. The data showed that there were no differences in the methylation levels of each Cytosine-phosphate-Guanine (CpG) site of PLAGL1 between full-term and preterm infants. Within preterm infants, the methylation levels of the CpG2, CpG3, CpG4, and CpG5 sites were increased in the chorioamnionitis group compared with the no chorioamnionitis group. The areas under curves (AUCs) of the receiver operating characteristic (ROC) curves of CpG2, CpG3, CpG4, and CpG5 were 0.656, 0.653, 0.670, and 0.712, respectively. Meanwhile, the methylation level of the CpG2 site was increased in preterm babies with brain injury compared with those without brain injury, and the AUC of CpG2 was 0.648, with a sensitivity of 75.9% and a specificity of 50.0%. A double luciferase reporter assay revealed that PLAGL1 fragments had enhancer-like activity and that the methylated form of PLAGL1 weakened this activity. Thus, PLAGL1 hypermethylation in chorioamniotic preterm infants is positively correlated with brain injury. Our results suggest a potential use for PLAGL1 methylation as a biomarker in the diagnosis of brain injury.

The distribution characteristics of strabismus surgery types in a tertiary hospital in the Central Plains region during the COVID-19 epidemic.

OBJECTIVE: This study aimed to analyze the distribution of different types of strabismus surgery in a tertiary hospital in Central China during the three-year period of the COVID-19 pandemic. METHODS: A retrospective analysis was conducted on the clinical data of strabismus patients who underwent surgery and were admitted to the Department of Strabismus and Pediatric Ophthalmology at the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022. RESULTS: A total of 3939 strabismus surgery patients were collected, including 1357 in 2020, 1451 in 2021, and 1131 in 2022. The number of surgeries decreased significantly in February 2020, August 2021, and November and December 2022. Patients aged 0-6 years accounted for 37% of the total number of strabismus surgery patientsr. The majority (60%) of all strabismus surgery patients were diagnosed with exotropia, with intermittent exotropia accounting for the highest proportion (53%). There was no statistically significant difference in the proportion of intermittent exotropia and constant exotropia during the three-year period (χ2 = 2.642, P = 0.267 and χ2 = 3.012, P = 0.221, respectively). Among patients with intermittent exotropia, insufficient convergence type was the most common form of strabismus (accounting for over 70%). Non-accommodative esotropia accounted for more than 50% of all internal strabismus cases. CONCLUSION: During the period from 2020 to 2022, the total number of strabismus surgeries in our hospital did not show significant fluctuations, but there was a noticeable decrease in the number of surgeries during months affected by the pandemic. Exotropia accounted for the highest proportion among strabismus surgery patients. Intermittent exotropia was the most common type among patients undergoing surgery for exotropia, and the most prevalent subtype was the insufficient convergence type. The age distribution of patients varied in different months, with a concentration of surgeries for strabismus patients in the 7-12 years old age group during the months of July and August each year.

Whole-tumor apparent diffusion coefficient histogram analysis for preoperative risk stratification in endometrial endometrioid adenocarcinoma.

OBJECTIVE: To investigate the application of whole-tumor apparent diffusion coefficient (ADC) histogram metrics for preoperative risk stratification in endometrial endometrioid adenocarcinoma (EEA). METHODS: Preoperative MRI of 502 EEA patients were retrospectively analyzed. Whole tumor ADC histogram analysis was performed with regions of interest drawn on all tumor slices of diffusion-weighted imaging scans. Risk stratification was based on ESMO-ESTRO-ESP guidelines: low-, intermediate-, high-intermediate-, and high-risk. Univariable analysis was used to compare ADC histogram metrics (tumor volume, minADC, maxADC, and meanADC; 10th, 25th, 50th, 75th, and 90th percentiles of ADC [recorded as P10, P25, P50, P75, and P90 ADC, respectively]; skewness; and kurtosis) between different risk EEAs, and multivariable logistic regression analysis to determine the optimal metric or combined model for risk stratifications. Receiver operating characteristic curve analysis with the area under the curve (AUC) was used for diagnostic performance evaluation. RESULTS: A decreasing tendency in multiple ADC values was observed from the low- to high-intermediate-risk EEAs. The (low + intermediate)-risk EEAs and low-risk EEAs had significantly smaller tumor volumes and higher minADCs, meanADCs, P10, P25, P50, P75, and P90 ADCs than the (high-intermediate + high)-risk EEAs and non-low-risk EEAs (all P < 0.05), respectively. The combined models of the (meanADC + volume) and the (P75 ADC + volume) yielded the largest AUCs of 0.775 and 0.780 in identifying the (low + intermediate)- and the low-risk EEAs from the other EEAs, respectively. CONCLUSION: Whole-tumor ADC histogram metrics might be helpful for preoperatively identifying low- and (low + intermediate)-risk EEAs, facilitating personalized therapeutic planning.

Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers.

Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.

Myeloid cell ACE shapes cellular metabolism and function in PCSK-9 induced atherosclerosis.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. This is due to increased lipid metabolism by macrophages which contributes to plaque resolution. However, the importance of ACE in peripheral blood monocytes, which are the primary precursors of lesional-infiltrating macrophages, is still unknown in atherosclerosis. Here, we show that the ACE-mediated metabolic phenotype is already triggered in peripheral blood circulating monocytes and that this functional modification is directly transferred to differentiated macrophages in ACE10/10 mice. We found that Ly-6Clo monocytes were increased in atherosclerotic ACE10/10 mice. The monocytes isolated from atherosclerotic ACE10/10 mice showed enhanced lipid metabolism, elevated mitochondrial activity, and increased adenosine triphosphate (ATP) levels which implies that ACE overexpression is already altered in atherosclerosis. Furthermore, we observed increased oxygen consumption (VO2), respiratory exchange ratio (RER), and spontaneous physical activity in ACE10/10 mice compared to WT mice in atherosclerotic conditions, indicating enhanced systemic energy consumption. Thus, ACE overexpression in myeloid lineage cells modifies the metabolic function of peripheral blood circulating monocytes which differentiate to macrophages and protect against atherosclerotic lesion progression due to better lipid metabolism.

MR Imaging of Epithelial Ovarian Neoplasms Part II: Malignant.

MR imaging shows high sensitivity and specificity for discriminating benign from malignant lesions, thereby aiding in cancer management from assessing the initial extent of disease to subsequent treatment response. Understanding the utility and application of advanced imaging techniques allows better lesion characterization. Subtypes of epithelial ovarian tumors are presented, along with characteristic imaging findings, and illustrated with examples. Select mimics of malignancy are also presented.

Clinical and chest computed tomography features associated with severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing: A multicenter, retrospective, observational study.

Chlamydia psittaci pneumonia is a rare disease with varying clinical presentations. Here, we aimed to investigate the clinical and chest computed tomography (CT) features of severe psittacosis pneumonia. Clinical data of 35 patients diagnosed with psittacosis pneumonia were retrospectively analyzed using metagenomic next-generation sequencing. The patients were classified into severe (n = 20) and non-severe (n = 15) groups. The median age of patients was 54 years, and 27 patients (77.1%) had a definite history of bird contact. Severe patients had more underlying comorbidities and were more prone to dyspnea and consciousness disorders than non-severe patients. The neutrophil count and D-dimer, lactate dehydrogenase, interleukin (IL)-2, IL-6, and IL-10 levels were higher, whereas the lymphocyte, CD3 + T cell, and CD4 + T cell counts, CD4+/CD8 + T cell ratio, and albumin level were substantially lower in severe patients than in non-severe patients. Chest CT findings of severe patients revealed large areas of pulmonary consolidation, and ground-glass opacities were observed in some patients, with a higher risk of involving multiple lobes of the lungs and pleural effusion. One patient died of multiple organ failure, whereas the condition of the other 34 patients improved, and they were discharged from the hospital. Patients with severe psittacosis pneumonia often have underlying comorbidities and are prone to developing dyspnea, consciousness disorder, and lesions in both lungs. Serum D-dimer, IL-2, IL-6, and IL-10 levels and lymphocyte, CD3 + T cell, and CD4 + T cell counts are associated with disease severity.

Emerging role of N6-methyladenosine RNA methylation in lung diseases.

In recent years, with the increase of air pollution, smoking, aging, and respiratory infection, the incidence rate and mortality of lung diseases are increasing annually, which has become a major hazard to human health. N6-methyladenosine (m6A) RNA methylation is the most abundant modifications in eukaryotes, and such modified RNA can be specifically recognized and combined by m6A recognition proteins and then mediate RNA splicing, maturation, enucleation, degradation, and translation. More and more studies have revealed that the m6A modification is involved in the pathogenesis and development of some diseases; however, the mechanisms of m6A in lung diseases are poorly understood. In this review, we summarize the latest progress in the biological function of m6A modifications in lung diseases and discuss the potential therapeutic and prognostic strategies. The dysregulation of global m6A levels and m6A regulators may affect the occurrence and development of asthma, chronic obstructive pulmonary disease, lung cancer, and other lung diseases through inflammation and immune function. In lung cancer, this modification has an important impact on malignant cell proliferation, migration, invasion, and drug resistance. In addition, abnormally changed m6A-modified proteins in lung cancer tissue samples and circulating tumor cells (CTCs) may be used as diagnostic and prognostic markers of lung cancer. Models composed of multiple m6A regulators can be used to evaluate the risk prediction or prognosis of asthma and pulmonary fibrosis. In general, the in-depth study of m6A modifications is a frontier direction in disease research. It provides novel insights for understanding of the molecular mechanisms underlying disease occurrence, development, and drug resistance, as well as for the development of effective novel therapeutics.

Clostridium perfringens and Escherichia coli Bacteremia in a Patient with Acute Obstructive Suppurative Cholangitis: A Case Report and Review of the Literature.

BACKGROUND Clostridium perfringens (CP), one of several clostridial species gram-positive bacteria, is a major cause of animal necrosis enteritis and traumatic gangrene. In some reports, CP can cause acute emphysematous cholecystitis in patients with biliary tract infections. However, C. perfringens combined with other aerobic bacteria (eg, E. coli) in bloodstream co-infection is extremely rare and often fatal. Herein, we present a case of co-infection to underscore this unusual situation so that clinicians can adequately evaluate and treat patients in time. CASE REPORT A 74-year-old man presented to the Emergency Department half a day after the onset of acute abdominal pain accompanied by nausea, vomiting, and chills. The patient was admitted, following development of jaundice, chills, high fever, confusion, and shock. Computed tomography (CT) revealed that the patient had cholangiectasis with acute obstructive suppurative cholangitis (AOSC). We subsequently performed percutaneous transhepatic gallbladder drainage surgery combined with antibiotics, including ceftriaxone, levofloxacin, and metronidazole. C. perfringens and Escherichia coli infections were identified by in vitro blood culture. Fortunately, the patient responded favorably to treatment in our hospital and was cured within 1 week. CONCLUSIONS We report a rare case of C. perfringens and E. coli bloodstream co-infection in a patient with AOSC. We suggest that anaerobic and aerobic co-infection should be considered in future clinical diagnoses. Effective antibiotic treatment combined with surgical drainage is crucial if mixed infection occurs.

Effect of regulation of the NRG1/ErbB4 signaling pathway on the visual cortex synaptic plasticity of amblyopic adult rats.

This study aimed to investigate the effect of the neuregulin-1/epidermal growth factor 4 (NRG1/ErbB4) signaling pathway on visual cortex synaptic plasticity in adult amblyopic rats with monocular deprivation (MD). Compared with the control group, the P wave latency and amplitude of the MD group were prolonged and low, respectively, with reduced synaptic plasticity-related protein expression, lower number of visual cortex neurons, and increased apoptosis of visual cortex neurons. Recombinant neuregulin-1 (rNRG1) administration activated the NRG1/ErbB4 signaling pathway and improved the visual cortex synaptic plasticity in MD amblyopic rats. However, the effects of rNRG1 were reversed by AG1478 (ErbB4 receptor blockers). The NRG1/ErbB4 signaling pathway in the parvalbumin neurons from MD rats was also inactivated. Amblyopic rats had significantly low cell activity and downregulated expression of synaptic plasticity-related proteins. Thus, exogenous administration of NRG1 can activate ErbB4 signal transduction and improve the damaged synaptic plasticity of the visual cortex among amblyopic rats. Further studies are warranted to explore the potential for clinical management of amblyopia.

[Effects of Acrolein on the Proliferation of and Per1 Gene Expression in Pulmonary Epithelial Cells].

OBJECTIVE: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. METHODS: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. RESULTS: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). CONCLUSION: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.

microRNA-362-3p targets USP22 to retard retinoblastoma growth via reducing deubiquitination of LSD1.

Accumulating evidence has reported the role of microRNA (miR) in retinoblastoma (RB). Therefore, the objective was to discuss how miR-362-3p exerted its function in RB cell progression via regulating ubiquitin-specific protease 2 (USP22) and lysine-specific histone demethylase 1 (LSD1). MiR-362-3p, USP22 and LSD1 expression in RB cells and tissues were tested. The biological functions of RB cells were detected via over-expressing miR-362-3p and down-regulating USP22. The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified. Down-regulated miR-362-3p and up-regulated USP22 and LSD1 were demonstrated in RB tissues and cells. Restoring miR-362-3p and depleting USP22 attenuated invasion, proliferation and migration, and facilitated apoptosis of RB cells. USP22 was a target gene of miR-362-3p. USP22 deubiquitinated LSD1 in RB. It is revealed that miR-362-3p targets USP22 and then restrains invasion, proliferation and migration while promotes apoptosis of RB via reducing LSD1 modified by deubiquitination.

Identification of Hub Genes as Biomarkers Correlated with the Proliferation and Prognosis in Lung Cancer: A Weighted Gene Co-Expression Network Analysis.

Lung cancer is one of the most malignant tumors in the world. Early diagnosis and treatment of lung cancer are vitally important to reduce the mortality of lung cancer patients. In the present study, we attempt to identify the candidate biomarkers for lung cancer by weighted gene co-expression network analysis (WGCNA). Gene expression profile of GSE30219 was downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed by the limma package, and the co-expression modules of genes were built by WGCNA. UALCAN was used to analyze the relative expression of normal group and tumor subgroups based on tumor individual cancer stages. Survival analysis for the hub genes was performed by Kaplan-Meier plotter analysis with the TCGA database. A total of 2176 genes (745 upregulated and 1431 downregulated genes) were obtained from the GSE30219 database. Seven gene co-expression modules were conducted by WGCNA and the blue module might be inferred as the most crucial module in the pathogenesis of lung cancer. In the pathway enrichment analysis of KEGG, the candidate genes were enriched in the "DNA replication," "Cell cycle," and "P53 signaling pathway" pathways. Among these, the cell cycle pathway was the most significant pathway in the blue module with four hub genes CCNB1, CCNE2, MCM7, and PCNA which were selected in our study. Kaplan-Meier plotter analysis indicated that the high expressions of four hub genes were correlated with a worse overall survival (OS) and advanced tumors. qRT-PCR showed that mRNA expression levels of MCM7 (p = 0.038) and CCNE2 (0.003) were significantly higher in patients with the TNM stage. In summary, the high expression of the MCM7 and CCNE2 were significantly related with advanced tumors and worse OS in lung cancer. Thus, the MCM7 and CCNE2 genes can be good indicators for cellular proliferation and prognosis in lung cancer.

Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3.

Gastric cancer (GC) is a common malignant tumor having poor prognosis globally. Circular RNA (circRNA) is a circular endogenous RNA generated by special selective splicing that occurs in various traits. Studies show that hsa_circ_0017639 is abnormally expressed and involved in tumorigenesis. Nevertheless, the hsa_circ_0017639 role in GC is unknown. This study detected hsa_circ_0017639 expression in a GC cell line using RT-qPCR. Subcellular localization of hsa_circ_0017639 was verified via FISH. We assessed correlations amongst miRNA, hsa_circ_0017639 and relative protein levels using luciferase reporter assays and RNA pulldown assays. The data illustrated that in hsa_circ_assays, expression was enhanced in GC cell. Downregulation of hsa_circ_0017639 decreased GC cell proliferation and migration in in vitro and in vivo experiments. RNA pulldown and RT-qPCR analysis verified that hsa_circ_0017639 sponged miR-224-5p. Bioinformatic and luciferase reporter assays validated that miR-224-5p and USP3 were downstream targets of hsa_circ_0017639. Upregulation of USP3 or downregulation of miR-224-5p restored proliferation and migration by MKN-28 and MGC-803 cells after hsa_circ_0017639 silencing. Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p. Our collective findings advised that hsa_circ_0017639 takes part in GC progression through regulating the miR-224-5p/USP3 axis, highlighting its potential as an effective GC therapeutic target.

ADH7, miR-3065 and LINC01133 are associated with cervical cancer progression in different age groups.

The aim of the present study was to identify potential therapeutic targets that serve crucial roles in the progression of cervical cancer. Clinical data, RNA sequencing (RNAseq)-counts and micro (mi)RNA data regarding cervical squamous cell carcinoma were retrieved from The Cancer Genome Atlas, and analyses were performed using the University of California Santa Cruz database. RNAseq and miRNA data were stratified into 3 groups (according to the patients' age), and genes were re-annotated and preprocessed prior to Mfuzz time clustering analysis. Subsequently, enrichment analyses were performed in order to identify differentially expressed mRNAs (DEmRNAs) and a protein-protein interaction analysis network was constructed. miRNA-gene, miRNA-lncRNA, and long non-coding (lnc)RNA-mRNA pairs were collected and the lncRNA-miRNA-mRNA competing endogenous (ce)RNA network was established. Further enrichment analyses were performed in order to identify crucial mRNAs in the ceRNA network. Finally, survival and drug association analyses were implemented. A total of 269 DEmRNAs [including alcohol dehydrogenase 7 (ADH7), vestigial-like family member 3 (VGLL3) and cytochrome P450, family 26, subfamily B, polypeptide 1 (CYP26B1)], 274 DElncRNAs (including LINC01133) and 16 DEmiRNAs (including miR-3065 and miR-330) were identified. There were 102 lncRNAs, 15 miRNAs, 15 mRNAs and 522 interaction pairs in the ceRNA network. In particular, ADH7 was regulated by miR-3065, and miR-3065 interacted with LINC01133 in the ceRNA network. Furthermore, ADH7 and CYP26B1 were enriched in the retinoic acid metabolic process and the retinol metabolism pathway. ADH7 and VGLL3 were significantly associated with the cervical cancer survival rate. ADH7, VGLL3, CYP26B1, miR-3065, miR-330, miR-499a and LINC01133 play pivotal roles in the progression of cervical cancer in different age groups.

Comparison of botulinum toxin with surgery for the treatment of acute acquired comitant esotropia and its clinical characteristics.

We compared the therapeutic effects between botulinum toxin and surgery for acute acquired comitant esotropia (AACE) and analyze its clinical characteristics. The data of the 29 cases, who received treatment for AACE in the Ophthalmic Center of the First Affiliated Hospital of Zhengzhou University and Henan Provincial Ophthalmology Hospital between January 2016 and January 2017, were collected. The 29 cases with AACE were followed for 6 months or more, and received either botulinum toxin injection (group A with 13 cases) or squint correction (group B with 16 cases). The distant and near deviation angles were compared between the two groups before and after treatment. The success rate (total horizontal deviation of 10 prism diopters or less) and stereopsis were compared between the two groups at post-treatment 6 months. At the same time, the relations between distant and near deviation angles were analyzed among different myopia levels and different AACE types. Results indicated that he success rate was not significantly different at post-treatment 6 months (84.6% vs 81.3%, P = 1.00). The distant and near deviation angles were all significantly different one day and one month after treatment (all P < 0.05); but at post-treatment 6 months, they were not significantly different (all P > 0.05) between the two groups. There were no significant differences in the distant and near stereoacuity between the two groups at post-treatment 6 months (all P > 0.05). Among the 25 cases with myopia, the pre-treatment distant deviation angle was significantly higher than pre-treatment near deviation angle in the cases with myopia level >-2.5 D (P < 0.05), and the pre-treatment distant and near deviation angles were all significantly higher in the cases with type-IIAACE than in the cases with type-IIIAACE (all P < 0.05). This study suggests that Botulinum toxin is as effective as surgery in the treatment of AACE at post-treatment 6 months. For the cases with myopia level >-2.5 D, the pre-treatment distant deviation angle is significantly higher than pre-treatment near deviation angle; and both pre-treatment distant and near deviation angles are greater in the cases with type-IIAACE than in the cases with type-IIIAACE.

Hepatitis B Virus X Protein-Induced Serine Protease Inhibitor Kazal Type 1 Is Associated with the Progression of HBV-Related Diseases.

OBJECTIVE: Hepatitis B virus (HBV) causes inflammation of the liver and is the leading cause of both liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Serine protease inhibitor Kazal type 1 (SPINK1) is an acute-phase response protein that is overexpressed in liver cancer tissue. This study investigated the clinical value of SPINK1 with regard to the diagnosis of HBV-related diseases and its regulatory mechanism. METHODS: Serum levels of SPINK1 in HBV-infected patients and healthy participants were detected by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to detect differential expression of SPINK1 mRNA and protein in HepG2 and HepG2.2.15 cells. The HBV infectious clone pHBV1.3 and its individual genes were cotransfected into HepG2 cells with the SPINK1 promoter coupled to a luciferase reporter; luciferase activity was measured, and the expression levels of SPINK1 were examined. RESULTS: Serum SPINK1 levels of HBV-infected patients were significantly higher than those of healthy participants, and the serum levels of SPINK1 in patients who tested positive for HBeAg were significantly higher than those in patients who tested negative for HBeAg. The serum SPINK1 levels of patients with LC or HCC were markedly higher than those of patients with chronic hepatitis. The HBV X protein (HBx) activated the SPINK1 promoter to upregulate expression of SPINK1 at both mRNA and protein levels. CONCLUSIONS: HBV enhances expression of SPINK1 through X. SPINK1 levels are increased during progression of HBV-related diseases and might be utilized as a biomarker for the diagnosis of HBV-related diseases.

Toxicologic evaluation of repetitive 4-week intravenous injections of midkine antisense oligonucleotide nanoliposomes in rats.

Midkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we report the 4-week sub-chronic toxicity of MK-ASODN nanoliposomes in SD rats. The adverse effects included loss of body weight gain and food consumption, peri-rhinal bleeding, piloerection, peri-anal filth, and kidney, liver, spleen, thymus, lung, and injection site lesions at high doses. Macroscopic changes were observed in the kidneys of the high-dose group, accompanied by a variation in urine protein and white blood cells, blood urea nitrogen, and serum creatinine. The increased spleen and liver coefficient, and the variation in circulating white blood cells, lymphocytes, and eosinophils in the high-dose group demonstrated that inflammation was caused by MK-ASODN nanoliposomes and was consistent with the macroscopic changes in the spleen and liver. The main necropsy findings of the animals that died were macroscopic changes in the lung. No severe toxic effects or mortalities occurred in the low- and medium-dose groups. However, a No Adverse Effect Level (NOAEL) was not identified since there were changes in organs deemed to be adverse at all dose levels. Thus, the maximum tolerated dose of MK-ASODN nanoliposomes for rats was considered to be 6 mg/kg/day.