OBJECTIVES: To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells. METHODS: The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both. RESULTS: LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown. CONCLUSIONS LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Cell Proliferation ; Cell Movement ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung ; Neoplasm Invasiveness ; A549 Cells ; Adenocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective:To screen the aging genes closely associated with pelvic organ prolapse(POP)by bioinformatics techniques,and to clarify the potential clinical significance and value of key genes.Methods:Gene Expression Omnibus(GEO)Database was used to download the datasets GSE53868 and GSE151188 for POP-related genes with the keyword"pelvic organ prolapse".The aging-related genes were obtained from Aging Atlas,CellAge,and the Human Ageing Genomic Resources(HAGR)Databases;the intersection of genes related with POP in two groups provided a list of differentially expressed genes(DEGs)associated with aging in POP;gene Set Enrichment Analysis(GSEA)was conducted with R software version 4.2.1;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis of DEGs were conducted by the Database for Annotation,Visualization and Integrated Discovery(DAVID);the protein-protein interaction(PPI)network was constructed with Cytoscape 3.9.1 software;the top 10 Hub genes were selected by cytoHubba plugin;the infiltration of 22 types of immune cells in the patients in POP group and control group was analyzed by CIBERSORT deconvolution method using R software;the key genes were further screened by LASSO regression algorithm;the correlation and diagnostic efficacy between key genes and immune cell infiltration were analyzed.Results:From the Aging Atlas,CellAge,and HAGR Databases,724 aging-related genes were identified.Intersection with the POP expression profile yielded an aging gene expression matrix related to POP containing 624 genes,and 29 POP-related DEGs were identified after differential analysis,including 2 upregulated genes and 27 downregulated genes.The GSEA results showed that the upregulated pathways were mainly related to diabetes and cellular senescence,whereas the downregulated pathways included Alzheimer's disease and hypoxia-inducible factor-1(HIF-1)signaling pathways.The GO functional enrichment analysis mainly enriched in the biological processes such as the response of the cells to lipopolysaccharide,inflammatory response,and negative regulation of cell proliferation.The KEGG signaling pathway enrichment analysis mainly enriched in interleukin-17(IL-17),tumor necrosis factor(TNF),and nuclear factor-kappa B(NF-κB)signaling pathways.The PPI network analysis got 10 Hub genes including interleukin-6(IL-6),interleukin-1B(IL-1B),prostaglandin-endoperoxide synthase 2(PTGS2),and NF-kappa-B inhibitor alpha(NFKBIA).The CIBERSORT deconvolution method results showed a relatively higher infiltration proportion of neutrophils and activated mast cells in the patients in POP group,the activated mast cells had a positive correlation with most of the DEGs(r>0.5)and the macrophages had a significant positive correlation with IL-1B(r>0.6).The key genes Jun D proto-oncogene(JUND),Snail homolog 1(SNAI1),amphiregulin(AREG),Lamin A/C(LMNA),and superoxide dismutase 2(SOD2)selected by LASSO regression analysis had high diagnostic efficacies,and the area under receiver operating characteristic curve(ROC)(AUC)were all greater than 0.75.Conclusion:During the aging process,the genes such as JUND,SNAI1,AREG,LMNA,and SOD2 may participate in the pathophysiology of POP through various pathways,including inflammation-related pathways,transcription regulation,and affecting collagen secretion and metabolism,thereby influence the connective tissue support function and promote the occurrence and development of POP.

Ophthalmic drug-device combination products are a new method of ophthalmic disease treatment,which is characterized by high bioavailability,strong targeting and good compliance.However,it is difficult for products to be developed and regulated due to the complexity of the human eye structure,drug-device interactions,and other factors.To provide a basis for guaranteeing the safety and efficacy of products development and management,the related regulations,current research,and evaluation of the quality of products are summarized in this paper.

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
Humans ; Carcinoma, Squamous Cell/therapy* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/therapy* ; Head and Neck Neoplasms ; Tumor Microenvironment

Objective:To verify the clinical safety and efficacy of new intelligent ventilation mode adaptive minute ventilation (AMV)+IntelliCycle ventilation in patients with mild-to-moderate acute respiratory distress syndrome (ARDS).Methods:The patients with mild-to-moderate ARDS, admitted to intensive care unit (ICU) of the First Affiliated Hospital of Jinzhou Medical University from February 2018 to February 2019, were enrolled in the study. The patients were divided into synchronous intermittent mandatory ventilation+pressure support ventilation (SIMV+PSV) group and AMV+IntelliCycle group according to the random number table method. All patients were given mechanical ventilation, anti-infection, analgesia and sedation, nutritional support and symptomatic treatment of primary disease after admission. SV800 ventilator was used for mechanical ventilation. In the AMV+IntelliCycle group, after setting the minute ventilation volume (VE), inhaled oxygen concentration (FiO 2) and positive end expiratory pressure (PEEP), the ventilator was turned on the full-automatic mode, and the preset value of VE percentage was 120%. In the SIMV+PSV group, the ventilator parameters were set as follows: the ventilation frequency was 12-20 times/min, the inspiratory expiratory ratio was 1∶1-2, the peak inspiratory pressure (PIP) limit level was 35-45 cmH 2O (1 cmH 2O = 0.098 kPa), and the setting of FiO 2 and PEEP was as the same as that of AMV+IntelliCycle group, the triggering flow was set to 2 L/min. All of the clinical parameters between the two groups were compared. The main outcomes were duration of mechanical ventilation, ventilator alarm times, manual operation times, and the mechanical power; the secondary outcomes were respiratory rate (RR), VE, tidal volume (VT), PIP, mouth occlusion pressure (P0.1), static compliance (Cst), work of breathing (WOB), and time constant at 0, 6, 12, 24, 48, 72, and 120 hours; and the blood gas analysis parameters of patients before and after ventilation were recorded. Results:A total of 92 patients with mild-to-moderate ARDS were admitted during the study period, excluding those who quit the study due to death, abandonment of treatment, accidental extubation of tracheal intubation and so on. Eighty patients were finally enrolled in the analysis, with 40 patients in SIMV+PSV group and AMV+IntelliCycle group respectively. ① Results of main outcomes: compared with the SIMV+PSV mode, AMV+IntelliCycle ventilation mode could shorten the duration of mechanical ventilation (hours: 106.35±55.03 vs. 136.50±73.78), reduce ventilator alarm times (times: 10.35±5.87 vs. 13.93±6.87) and the manual operations times (times: 4.25±2.01 vs. 6.83±3.75), and decrease the mechanical power (J/min: 12.88±4.67 vs. 16.35±5.04, all P < 0.05). But the arterial partial pressure of carbon dioxide (PaCO 2) of AMV+IntelliCycle group was significantly higher than that of SIMV+PSV group [mmHg (1 mmHg = 0.133 kPa): 41.58±6.81 vs. 38.45±5.77, P < 0.05]. ② Results of secondary outcomes: the RR of both groups was improved significantly with the prolongation of ventilation time which showed a time effect ( F = 4.131, P = 0.005). Moreover, compared with SIMV+PSV mode, AMV+IntelliCycle mode could maintain a better level of RR, with intervention effect ( F = 5.008, P = 0.031), but no interaction effect was found ( F = 2.489, P = 0.055). There was no significant difference in VE, PIP, P0.1 or Cst between the two groups, without intervention effect ( F values were 3.343, 2.047, 0.496, 1.456, respectively, all P > 0.05), but they were significantly improved with the prolongation of ventilation time in both groups, with time effect ( F values were 2.923, 12.870, 23.120, 7.851, respectively, all P < 0.05), but no interaction effect was found ( F values were 1.571, 1.291, 0.300, 0.354, respectively, all P > 0.05). The VT, WOB or time constant in both groups showed no significant changes with the prolongation of ventilation time, and no significant difference was found between the two groups, there was neither time effect ( F values were 0.613, 1.049, 2.087, respectively, all P > 0.05) nor intervention effect ( F values were 1.459, 0.514, 0.923, respectively, all P > 0.05). Conclusion:AMV+IntelliCycle ventilation mode can shorten the ventilation time of patients with mild-to-moderate ARDS, reduce mechanical power, and reduce the workload of medical care, but PaCO 2 in the patients with AMV+IntelliCycle mode is higher than that in the patients with SIMV+PSV mode.

Objective To study the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted MRI in differentiating benign from malignant breast lesions.Methods 50 female patients with lesions verified by pathology were included in this study,all of them underwent multi-b value (b=0-2000s/mm2) DWI scanning.Tissue diffusivity (D),pseudo-diffusivity (D*),perfusion fraction (f) and apparent diffusion coefficient (ADC) were acquired using IVIM model.The difference of these parameters in benign and malignant breast lesions was analyzed statistically.The diagnostic performance of these parameters was evaluated by ROC analysis.Results In benign lesions,D,D*,f and ADC value was (1.31±-0.47) ×10-3 mm2/s,(26.47±13.81) ×10-3 mm2/s,(17.35±3.78)％,(1.37±0.37)×10-3 mm2/s,respectively.In malignant lesions,D,D*,f and ADC value was(0.95±0.28)×10-3 mm2/s,(24.58±14.62)×10-3 mm2/s,(23.69±4.35)％,(1.03±0.14)×10-3 mm2/s,respectively.There were statistically significant differences between benign and malignant lesions in D,f and ADC value (t=3.203,-5.139,3.991,P＜0.05).There was no statisticaly significant difference in D* value (P＞0.05).ROC analysis showed that AUC of D value was 0.866,which was the highest one.AUC was increased to 0.934 by combining D with f value for diagnosis.Condusions The parameters acquired from IVIM model are useful to differentiate benign from malignant breast lesions.D value obtained from IVIM model may have relatively high sensitivity and specificity,D Combined with f value can obtain the best diagnostic performance.

Objective To investigate the protective effect of mild hypothermia on cerebral ischemia-reperfusion injury in rats and the effect of mild hypothermia on the expression of inhibitor of differentiation 2 (Id2) protein.Methods A total of 72 adult male rats were randomly divided into a sham operation group,a normothermia group,and a mild hypothermia group.A model of middle cerebral artery occlusion was induced by a suture method.The mild hypothermia group was treated with low temperature (anal temperature 33±1 ℃,tympanic membrane temperature 31±1 ℃).Modified Neurological Severity Score (mNSS) was used to evaluate neurological deficits,triphenyltetrazolium chloride staining was used to detect infarct volume,and Western blot was used to detect the Id2 expression in the ischemic cortex at ischemia-reperfusion 6,12,24,and 72 h,respectively.ResultsThe mNSS scores in the mild hypothermia group were significantly lower than those in the normothermia group,the infarct volumes were significantly smaller than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.001).Western blot analysis showed that the Id2 expressions in the ischemic cortex in the mild hypothermia group were significantly lower than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.05).Conclusion s Mild hypothermia can decrease neurological deficits and reduce infarct volume after cerebral ischemia-reperfusion,its mechanism may be associated with the down-regulation of the Id2 expression.

Objectives To investigate the occipital cortex metabolite alterations in repetitive and severe neonatal hypoglycemia rats treated with sodium pyruvate and to reveal the protective role of sodium pyruvate using high resolution 1H nuclear magnetic resonance spectroscopy.Methods Thirty-six 2-dayold Sprague-Dawley rats were randomly divided into hypoglycemia group and pyruvate group with 18 rats in each group.Rats in both groups received intraperitoneal injections of insulin (40 U/kg body weight) at 2,4 and 6 days of age to induce severe hypoglycemia (blood glucose value ≤ 1.4 mmol/L).In the hypoglycemia group,2.5 hours after insulin injection,intraperitoneal injection of 50％ glucose (2 ml/kg) was administered to terminate hypoglycemia,while in the pyruvate group,50％ glucose (2 ml/kg) and sodium pyruvate solution 2.5 ml/kg (500 mg/kg) were injected.Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to observe the status of injured neurons in six neonatal rats,and metabolite changes in occipital cortex of the other 12 rats were detected by 1H nuclear magnetic resonance spectroscopy.The difference between the two groups was compared by independent-samples t test.Results Neonatal rats of both groups reached severe hypoglycemia level 2.5 hours after insulin injection.Compared with hypoglycemia group,pyruvate group had fewer injured neurons (45±5 vs 113 ± 12,t=0.782,P=0.013) and lower injured index in the occipital cortex (0.15 ± 0.03 vs 0.36 ± 0.06,t=l.143,P=0.020).Pyruvate group showed significant decreases in the concentration of taurine [(13.31 ± 2.06) vs (18.44 ± 3.86) mol/kg,t=8.231],glutamine[(1.50 ± 0.24) vs (2.02 ± 0.40) mol/kg,t=3.137],glutamate[(7.04 ± 0.95) vs (9.40 ± 1.73) mol/kg,t=6.449],aspartate[(1.51 ± 0.28) vs (2.15 ± 0.58) mol/kg,t=2.561] and creatine [(6.37±0.99) vs (8.46± 1.77) mol/kg,t =4.226] in the occipital cortex (all P'＜0.017).Conclusions Simultaneous use of glucose and sodium pyruvate to terminate hypoglycemia in repetitive and severe neonatal hypoglycemia rats can effectively alleviate severe hypoglycemia-induced occipital lobe damage via regulating excitatory amino acid neurotransmitters,energy metabolism and other metabolic pathways.

Objective To explore the significance of expressions of glutamate transporters and γ-aminobutyric acid transporters in the rat model with cerebral ischemia.Methods The detections of the expressions of glutamate transporter-1 (EAAC-1) and γ-aminobutyric acid transporter-1 (GAT-1) in models with ischemia in vivo and hypoxia in vitro were performed by immunofluorescence,Westen-blot and real-time polymerase chain reaction (RT-PCR) methods.Results The expression of EAAC1 was reduced in the cerebrum of focal cerebral ischemic MACO rat model as well as in primary neurons cultured under hypoxia.The expression of GAT1 was elevated.Conclusion EAAC1 expression decreases while GAT1 expression increases under condition of cerebral ischemia and anoxia.

Objective To explore the significance of expressions of glutamate transporters and γ-aminobutyric acid transporters in the rat model with cerebral ischemia.Methods The detections of the expressions of glutamate transporter-1 (EAAC-1) and γ-aminobutyric acid transporter-1 (GAT-1) in models with ischemia in vivo and hypoxia in vitro were performed by immunofluorescence,Westen-blot and real-time polymerase chain reaction (RT-PCR) methods.Results The expression of EAAC1 was reduced in the cerebrum of focal cerebral ischemic MACO rat model as well as in primary neurons cultured under hypoxia.The expression of GAT1 was elevated.Conclusion EAAC1 expression decreases while GAT1 expression increases under condition of cerebral ischemia and anoxia.