Study on the association between sleep deficiency and myopia in children and adolescents / 中国学校卫生

Abstract@#In recent years, the overall prevalence of myopia has been increasing in China, towards younger age at onset and greater severity. Studies have shown that the occurrence and progression of myopia are affected by environmental and behavioral factors, e.g. prolonged near concentration and lack of outdoor activities. In recent years, studies on the association between insufficient sleep and myopia have increased. Domestic and foreign studies have found that there is a positive correlation between insufficient sleep and the occurrence of myopia in children and adolescents, but the results are not uniform. Therefore, this paper reviews the epidemiology and possible mechanism of sleep deprivation and myopia in children and adolescents, in order to provide theoretical basis for sleep improvement and myopia prevention in children and adolescents.

Placement of a Jejunal Feeding Tube via an Ultrasound-Guided Antral Progressive Water Injection Method.

BACKGROUND: Jejunal feeding tube allows the nutrition of critical care patients more easy and safe. However, its placement remains a challenge. This study aimed to introduce a jejunal feeding tube through an ultrasound-guided antral progressive water injection method and subsequently to examine its efficacy. METHODS: Between April 2016 and April 2017, 54 patients hospitalized in the Department of Critical Care Medicine, Peking Union Medical College Hospital, China who needed nutritional support through a jejunal feeding tube were recruited for this study. Patients who applied ultrasound-guided antral progressive water injection method were classified into the experimental group. Patients who applied conventional method were registered as control group. RESULTS: No significant differences were found in age, body mass index, and Acute Physiology and Chronic Health Evaluation score, but a significant difference in operation time was found between the experimental group and the control group. Of the 24 individuals in the control group, 17 displayed clear catheter sound shadows once the tube entered the esophagus. In comparison, of the 30 individuals in the experimental group, all harbored catheter sound shadows through the esophageal gas injection method. Subsequent observation revealed that in the control group (via ultrasonographic observation), 15 individuals underwent successful antral tube entry, for a success rate of 63%. In the experimental group (via antral progressive water injection), 27 individuals underwent successful antral tube entry, for a success rate of 90%. There was a significant difference between the success rates of the two groups (χ2 = 5.834, P = 0.022). CONCLUSION: The antral progressive water injection method for the placement of a jejunal feeding tube is more effective than the traditional ultrasonic placement method.

PKM2, a potential target for regulating cancer.

Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells. Recent years, more and more research suggested PKM2 plays a crucial role in cancer progression through both metabolic and non-metabolic pathways. On the one hand, the middle product of glycolysis, such as amino acids, nucleotides, lipids is necessary to rapid growth of cancer cells. On the other hand, PKM2 supports tumor growth through regulating the expression of gene that involved in cell proliferation, migration and apoptosis. In this article, we review the recent advances to further understand the regulation and function of PKM2 in tumorigenesis. Given its multiple effects on cancer, PKM2 may be a potential target for cancer diagnosis and treatment.

Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation.

AIM: To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. METHODS: Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes' expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. RESULTS: In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. CONCLUSION: These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis.

RICTOR expression in esophageal squamous cell carcinoma and its clinical significance.

Esophageal cancer is one of the most common malignant tumors in the world, and its incidence is the eighth highest; meanwhile, its fatality rate is the sixth highest. The PI3K/Akt/mTOR signaling pathway plays a required role in human cancer, including cell survival, metabolism and migration. As a kind of important scaffold protein in mTORC2, RICTOR has showed over-expression in several malignancies like melanoma and endometrial cancer. In this research, we selected 201 cases of paraffin specimens from patients diagnosed as esophageal squamous cell carcinoma after surgical treatment and then estimated the RICTOR expression in each esophageal squamous cell carcinoma tissue by using the immunohistochemical streptavidin-peroxidase technique. Then, we analyzed the association among the clinicopathological parameters, the prognosis and the expression of RICTOR. Eventually, we found that the percentage of RICTOR-positive expression in 201 ESCC samples is 70.6% (142/201) and the figure for RICTOR-negative or RICTOR-doubtful-positive expression is 29.4% (59/201). RICTOR expression positively correlated with ESCC patients' AJCC stage (P = 0.011) and showed an opposite trend with survival (P = 0.007). Based on univariate and multivariate Cox proportional hazards regression analysis, RICTOR-positive expression, AJCC staging III or IV and nodal metastasis are prognostic factors and the former two are independent risk factors for ESCC. In conclusion, our study showed potential that targeting RICTOR may represent new effective inhibitors for treating ESCC.

Exosomes derived from gefitinib-treated EGFR-mutant lung cancer cells alter cisplatin sensitivity via up-regulating autophagy.

Several clinical trials indicate that concurrent administration of tyrosine kinase inhibitors (TKIs, such as gefitinib or erlotinib) with chemotherapy agents fails to improve overall survival in advanced non-small cell lung cancer (NSCLC) patients. However, the precise mechanisms underlying the antagonistic effects remain unclear. In the present study, we investigated the role of exosomes in the antagonistic effects of concurrent administration of chemotherapy and TKIs. Exosomes derived from gefitinib-treated PC9 cells (Exo-GF) decreased the antitumor effects of cisplatin, while exosomes derived from cisplatin-treated PC9 cells (Exo-DDP) did not significantly affect the antitumor effects of gefitinib. Additionally, inhibition of exosome secretion by GW4869 resulted in a modest synergistic effect when cisplatin and gefitinib were co-administered. Furthermore, Exo-GF co-incubation with cisplatin increased autophagic activity and reduced apoptosis, as demonstrated by an upregulation of LC3-II and Bcl-2 protein levels and downregulation of p62 and Bax protein levels. Thus, the antagonistic effects of gefitinib and cisplatin were mainly attributed to Exo-GF, which resulted in upregulated autophagy and increased cisplatin resistance. These results suggest that inhibition of exosome secretion may be a helpful strategy to overcome the antagonistic effects when TKIs and chemotherapeutic agents are co-administered. Before administering chemotherapy, introducing a washout period to completely eliminate TKI-related exosomes, may be a better procedure for administering chemotherapy and TKIs.

Autophagy Inhibition Overcomes the Antagonistic Effect Between Gefitinib and Cisplatin in Epidermal Growth Factor Receptor Mutant Non--Small-Cell Lung Cancer Cells.

BACKGROUND: Four large clinical trials have shown that concurrent administration of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), such as gefitinib or erlotinib, with chemotherapy agents does not improve overall survival (OS) in unselected patients with advanced non-small-cell lung cancer (NSCLC). In the present study, the role of autophagy in the combination of gefitinib and cisplatin on EGFR-TKI-sensitive human lung cancer cell line was investigated. Moreover, whether simultaneous autophagy inhibition treatment increases the antitumor activity was explored. MATERIALS AND METHODS: The PC9 cell was exposed to either gefitinib or cisplatin alone or together. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cytotoxic interaction between gefitinib and cisplatin was determined using coefficient of drug interaction (CDI) analysis. The cell cycle distribution and apoptosis were measured using flow cytometry. Alterations in the autophagy and apoptosis signaling pathway were measured using Western blot assays. RESULTS: Coadministration of gefitinib and cisplatin resulted in antagonistic activity to tumor cell proliferation. However, the addition of chloroquine (CQ), an autophagy inhibitor, overcame the antagonistic effects, as demonstrated by CDI analysis and Annexin V-FITC/propidium iodide (PI) assays. In addition, gefitinib administration led to cell G1 phase arrest, which might have contributed to the antagonistic activity between gefitinib and cisplatin. However, the addition of CQ did not deregulate cell cycle arrest, indicating that other mechanisms might be involved. The Annexin V-FITC/PI assays showed that the addition of CQ significantly the increased the ratio of apoptosis cells. Also, immunoblotting assays exhibited increased Bax and decreased Bcl-2, suggesting that autophagy inhibition by CQ could increase cell apoptosis and thus overcome the antagonistic effects. CONCLUSION: The combination of gefitinib with cisplatin generates antagonistic effects on EGFR-TKI-sensitive cells. However, inhibiting autophagy produces a synergistic effect, suggesting that gefitinib and cisplatin combined with an autophagy inhibitor (especially CQ) might be a beneficial strategy to overcome the antagonistic effects between EGFR-TKIs and chemotherapeutic agents.