Recent studies have indicated that miRNA is an important element that regulates gene expression at the post transcriptional level. MiRNAs play important roles in development and progression of chronic disorders of many organs. This. review summarizes the recent researches on the association of miRNA with chronic liver diseases.

Objective To evaluate the clinical efficacy and safety of different courses of topical tacrolimus 0.1％ ointment in facial corticosteroid-dependent dermatitis and to observe the rebound in patients after treatment with these regimens.Methods A total of 104 patients with facial corticosteroid-dependent dermatitis were randomly divided into 3 groups to be treated with topical tacrolimus 0.1％ ointment twice daily for 4,8 and 16 weeks respectively.The patients were followed up every 2 weeks within the early 4 weeks of treatment and every 4 weeks thereafter.The rebound phenomena was observed in patients on week 4 after the withdrawal of tacrolimus.Results Finally,90 patients completed this trial,including 32 patients in the 4-week group,29 patients in the 8-week group and 29 patients in the 16-week group.No significant differences were observed between the 4-,8- and 16-week groups in the total reponse rate (75.00％,82.76％,86.21％,respectively,x2 =1.35,P ＞ 0.05).The rebound rate in the 16-week group significantly differed from that in the 4- and 8-week group (20.69％ vs.46.88％ and 41.38％,both P＜ 0.05),while no statistical difference was noted between the 4- and 8-week groups.Local burning and itching were reported in 31.73％ of these patients,and all of these irritant reactions occurred within the first week of treatment.Conclusions Topical tacrolimus 0.1％ ointment is safe and effective for the treatment of facial corticosteroid-dependent dermatitis.The total response rate does not increase with the extended treatment course,and 4 weeks of treatment is enough for the marked and stable improvement of facial corticosteroid-dependent dermatitis,but the rebound rate is likely to be reduced by extended treatment course.

Apoptosis ; Gene Expression Profiling ; Hepatic Stellate Cells ; pathology ; Humans ; Liver ; metabolism ; Liver Cirrhosis ; genetics ; metabolism ; pathology ; Liver Diseases ; genetics ; metabolism ; pathology ; MicroRNAs ; metabolism ; physiology ; Transforming Growth Factor beta1 ; metabolism

Objective To investigate the photo-protective mechanisms of hydroxychloroquine and epigallocatechin gallate (EGCG) on HaCaT cells damaged from UVB irradiation. Methods Subconfluent HaCaT cells were irradiated with different doses of UVB irradiation and treated with the above listed agents. The mRNA expression levels of p53, p21, c-fos and GADPH genes were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Results UVB irradiation induced mRNA expression of p53, p21 and c-fos in cultured HaCaT cells, which were alleviated by hydroxychloroquine and EGCG treatment in UVB irradiation group. Conclusions The photo-protective effects of hydroxychloroquine and EGCG on HaCaT cells by UVB irradiation might be related to inhibition of the expression of p53,p21 and c-fos genes.

Objective To compare genomic expression differences between androgenic complete hydatidiform mole (AnCHM) and normal first trimester villi with similar gestation weeks,and search for potential adjuvant diagnostic molecular markers.Methods Short tandem repeat (STR) detection was used to identify AnCHM,human oligonucleotide array U133 Plus 2.0 was used to measure genomic expression differences between AnCHM and normal villi,and quantitative fluorescent RT-PCR was used to verify array of several genes.Results Nine of 11 histologically diagnosed complete hydatidiform moles were found to be AnCHM by means of STR,and the other 2 were biparental complete hydatidifonn mole (BiCHM). Compared with villi,oligonueleotide array showed 279 genes (0.72%,279/38 500) were over expressed and 1710 genes (4.44%,1710/38 500) under expressed in AnCHM.Bioinformatics analysis found that differentially expressed genes were involved in multiple biological processes and pathways.Changes of imprinting genes,growth hormone genes and chorionie somatomammotropin hormone genes were especially remarkable.Conclusions Pathogenesis of AnCHM is a complex process involving multiple genes and pathways.Altered expression of imprint genes may play important roles in the process.

BACKGROUNDNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.

METHODSOne hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.

RESULTSTransmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of a-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2 +/- 2.7) microg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8 +/- 12.3) microg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of a-granules (r = 0.514, P < 0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r = 0.84, P < 0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose a-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, chi(2) = 17.38, P < 0.01).

CONCLUSIONSThere are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets may play an important role in the generation and growth of lung cancer. These changes can be used as a diagnostic index of severity, progression, and prognosis of NSCLC.

Adult ; Aged ; Blood Platelets ; ultrastructure ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; mortality ; ultrastructure ; Female ; Humans ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; P-Selectin ; blood ; Survival Analysis

Clinical phenotype and gene characteristics of a patient diagnosed with Imerslund-Gr?sbeck syndrome (IGS) in Department of Neurology, Children′s Hospital of Soochow University in December 2018 were analyzed retrospectively, and literature review was conducted.The 16 years and 5 months old boy was admitted to the hospital with symptoms of weakness of lower limbs for 2 weeks.He had a history of megaloblastic anemia and isolated proteinuria.Genetic metabolism of hematuria showed methylmalonic academia.Genetic analysis revealed a compound heterozygous AMN gene mutation[c.742C>T(p.Q248 *) and c. 761G>A(p.G254E)]. These two mutations were derived from his parents respectively, which had been reported before.Symptoms of the patient improved after intramuscular administration of hydroxycobalamin and oral betaine.Review of the literature indicated that the clinical manifestations of AMN gene-related IGS were mostly megaloblastic anemia and isolated proteinuria, and the older children might suffer from neurological symptoms such as movement disorders, dementia, delirium or psychosis.The clinical phenotype of this disease was variable, which might easily lead to misdiagnosis.The patient presented with a special phenotype of mild reversible peripheral neuropathy, which expanded the clinical phenotype of pathogenic genes of AMN gene.In addition, peripheral neuropathy caused by vitamin B 12 metabolic disorders is reversible, and it is suggested to measure vitamin B 12, test related genes and treatment with vitamin B 12 in peripheral neuropathy of unknown etiology.

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Objective To evaluate the clinical efficacy between stereotactic body radiotherapy (SBRT) and surgical treatment for stage Ⅰ-Ⅱ non-small cell lung cancer (NSCLC).Methods Clinical data of 120 patients with early-stage NSCLC who underwent SBRT or surgical treatment in Zhejiang Cancer Hospital from 2012 to 2015 were retrospectively analyzed.Propensity score matching was carried out between two groups.Sixty eligible patients were enrolled in each group.In the SBRT group,the 80％ isodose line covered 95％ of the planning target volume,and the 100％ isodose line covered 100％ of the internal gross tumor volume.The fractional dose was 5-15 Gy and the median biologically equivalent dose was 100 Gy (range:57.6-150.0 Gy).In the operation group,32 patients underwent video-assisted thoracoscopic lobectomy and 9 patients underwent wedge resection or segmentectomy.Results All patients successfully completed corresponding treatment and were followed up.The median follow-up was 32.3 months (range:8.6-68.4 months).In the operation group,3 patients died from infection within postoperative 90 d,whereas no case died in the SBRT group (P=0.079).In the SBRT group,3 patients died of other factors besides tumor (cerebral infarction,heart disease,etc.) during follow-up.Local-regional recurrence occurred in 12 patients including 5 cases in the operation group and 7 in the SBRT group (P=0.543).In the operation group,11 patients experienced distant metastases with a median disease-free survival (DFS) of 33.5 months.In the SBRT group,6 patients had distant metastases and the median DFS was 38.4 months (P=0.835,P=0.178).In the SBRT group,the 1-and 3-year overall survival rates were 93％ and 83％,and 95％ and 83％ in the operation group (P=0.993).Conclusions The 1-and 3-year overall survival rates and local control rate do not significantly differ between SBRT and operation for patients with early-stage NSCLC.

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.
Ascorbic Acid ; Cysteine ; Humans ; Infant, Newborn ; Metabolomics ; Methionine ; Neonatal Sepsis ; Pyruvates ; Sepsis