Epithelial-mesenchymal transition (EMT) refers to tne transition during which epithelial cells undergo the loss of apical-basal polarity, acquisition of migration capability and transformation into mesenchymal cells. EMT induces breast cancer in situ to developing into metastasis and associates with the drug resistence. The multiple elements including signal pathways, transcriptional factors and downstream genes orchestrate the transition. Among them, the transforming growth factor β (TGF-β) signaling pathway plays a key role in the regulation of EMT in breast cancer. And this paper reviews the development of TGF-β signaling pathway induced EMT in breast cancer.
Breast Neoplasms ; metabolism ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Humans ; Signal Transduction ; Transcription Factors ; Transforming Growth Factor beta ; physiology

Objective To provide an effective basis for clinical control methods of multi-drug-resistant bacterial (MDRB) infections by analyzing the distribution and antimicrobial resistance of MDRB.Methods The French Merieux ATB Expression Automated Analysis System was used for bacterial identification,whereas a drug susceptibility testing was performed by K-B methods.Drug-resistance rate was calculated,and the predisposing factors were analyzed.Results Altogether 811(8.1％) strains were isolated from 9 954 specimens,and the majority of multiply antimircobial-resistant bacteria were Escherichia coli,Coagulase-negative staphylococci,Klebsiella Pneumoniae Staphylococcus aureus,Acinetobacter Baumannii,Pseudommonas aeruginosa,whereas the last two appeared pan resistant strains.Specimen source was mainly from respiratory specimens,accounted for 47.8％,and was mainly distributed in the ICU unit,atout41.8％ ;MDRB enterobacter was highly sensitive to Carbapenems with resistance rates less than 1.5％ and to Amikacin and other inhibitor drugs that rate was less than 30.0％.The resistance rates of MDRB nonfermentative bacteria was ＞ 77.0％ to Carbapenem antibacterial drugs whereas to non-resistance was found to polymyxin and only 20.0％ resistance rate to Cefoperazone/sulbactam.MDRB staphylococcus was 100.0％ sensitive to Vancomyci,Teicoplanin and Linezolid and less sensitive (＜ 30.0％) to chloramphenicol and rifampicin.MDRB showed high resistance rate to other antibacterial drugs.The predisposing factors included age,other disease,hospitalization over two weeks,the usage of multiply antimicrobial especially cephalosporins overtoppinh 7 days,and invasive operations.Conclusion The major MDRBs are resistant to common-used antimicrobial drugs.It is nesessary to pay attention to the differences.

Objective To explore the clinical characteristics of critically ill children infected with pseudomonas aeruginosa(PA) and PA antibiotics resistance in pediatric intensive care unit (PICU).Methods Case records of children with PA infection admitted to PICU in children′s hospital affiliated to Shanghai Jiaotong University from Jan 2007 to Dec 2009 were reviewed for clinical characteristics,case fatality rate,prognosis and drug resistance.Results (1) Clinical features:12 cases were community-acquired infection and 46 cases were hospital-acquired infections in 58 cases.On the same period,hospital-wide surveillance obtained PA 232 strains,PICU obtained PA 112,the ratio was 48.3%.Twelve cases died and total mortality was 20.7%.The mortality was significantly difference between community-acquired infections (5 cases,41.6%)and hospital-acquired infections (7 cases,15.2%)(P<0.05).The main symptom of children with community-acquired infections were intestinal infection (5 cases) and sepsis (5 cases).The children had acute onset and developed to shock and multiple organ dysfunction syndrome rapidly.Laboratory examination revealed the white blood cell normal (7/12) and decreased in 5 cases (5/12).The value of C-reactive protein was increased significantly,and the concentration of blood endotoxin were also increased.In the hospital-acquired PA infection cases,the main symptom was respiratory abnormal (38 cases),worsen primary disease,extended staying days in PICU.(2)Drug resistance analysis:112 PA,69.8% of ceftazidime-resistant,72.8% of the imipenem-resistant.Conclusion There is significant difference of the clinical features between PA community-acquired infection and hospital-acquired infection.The former is mostly primary infections with high fatality rate.PA hospital-acquired infection has become an important pathogen of nosocomial infection in PICU.And it is important to prevent PA infection caused by a long term broad-spectrum antibiotics application and invasive medical procedures.

AIM: To investigate the potential role of 14-3-3 tau in trophoblast cells on invasiveness. METHODS: 14-3-3 tau expression was detected in first-trimester villi, deciduas and human trophoblastic cell line (BeWo) by immunohistochemistry. Small interference RNA (siRNA) targeting 14-3-3 tau was transfected into BeWo cells. The effects of down-regulated 14-3-3 tau on invasion of human trophoblasts cell line BeWo were examined by matrigel invasion assay, and the transcription, translation of E-cadherin and snail were estimated by RT-PCR or Western blotting. U0126 was used to detect the extracellular-signal related kinase 1/2 (ERK1/2) function on down-regulation of 14-3-3 tau induced cell invasion. RESULTS: 14-3-3 tau was detected in the invasive trophoblastic cells in the first trimester villi and that invaded to the deciduas. BeWo cells also expressed 14-3-3 tau. Down-regulation of 14-3-3 tau increased the invasive cell-number of BeWo, as well as the expression of snail, and inhibited E-cadherin. U0126 inhibited the enhanced invasiveness in these cells induced by the down-regulation of 14-3-3 tau. CONCLUSION: 14-3-3 tau may regulate the invasiveness of human trophoblastic cells through ERK1/2 signaling pathway.

Objective To explore the role of p38MAPK and TGF?2 in the development of diabetic retinopathy.Methods Fifteen Hamsters were induced into diabetic models by intraperitoneal injection of Streptozotocin(40 mg/kg once a day) for 3 d and 13 Hamsters were successfully established,whose blood glucose was over 13.5 mmol/L.Ten Hamsters as controls were intraperitoneally injected of physical saline of the same volume.At 16th week after induction,the total RNA of retina from all sacrificed Hamsters was collected.The mRNA expressions of p38MAPK,TGF?2 in retina were detected by semi-quantitative RT-PCR and their protein levels by Western blotting.Results The mRNA expressions of p38MAPK,TGF?2 in retina were of high tendency and their protein levels increased.Conclusion p38MAPK signal pathway may involve in the pathogenesis of diabetic retinopathy.

Objective To observe the expression of insulin receptor mRNA in skeletal muscle and the change of oxidative stress in diabetic rats at different intensity training.Methods Sprague-Dawley rats were divided into group A(control group),group B(non-exercise group),group C(low-intensity exercise group),group D(moderate-intensity exercise group) and group E(high-intensity exercise group),6 rats in each group.A diabetic rat model was induced by injecting streptozotocin(STZ)for 4 weeks after high lipid and glucose breeding.Rats were trained for 6 weeks on a treadmill.Serum glucose and insulin,insulin resistance index(HOMA-IR),activities of SOD and GSH-Px,and MDA were detected before and after training.Expression levels of InsR mRNA in skeletal muscle were measured by RT-PCR.Results The InsR receptor mRNA expression level in three exercise groups at different intensities was 0.55?0.05,0.53?0.04,and 0.41?0.05,respectively,and was significantly higher in low and moderate intensity exercise groups than in group B (P

·AIM: Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents,which can reduce choroidal blood flow resistance, might prevent the development of choroidal neovascularization (CNV). D-Timolol and L-Timolol are hypotensive agents used in cardiovascular and glaucoma therapy. Their effects on laser-induced experimental CNV rat model and human umbilical vein endothelial cells (HUVEC) were thus evaluated.·METHODS: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. D-Timolol and L-Timolol were given once daily through intraperitoneal injection after laser treatment for 4wk. Fluorescein angiography was performed on 2wk and 4wk. HUVEC were tested by proliferation assay and adhesion assay with D-Timolol and L-Timolol at different concentrations.· RESULTS: D-Timolol reduced the fluorescein leakage to 83% of the control group in laser-induced rat's CNV model at a dosage of 15mg/(kg·d). L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/(kg·d). D-Timolol inhibited the endothelial cells proliferation significantly by 300mg/L. L-Timolol also significantly inhibited the cell proliferation at 1 000mg/L. But at a lower dose such as 300mg/L, no significant inhibitory effect was found. Both drugs showed no effect on cell adhesion function in cell culture experiments.· CONCLUSION: D-Timolol was found to prevent CNV development in laser-induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. L-Timolol had no effect on cell proliferation at the same dose, and neither on rat CNV model. The results indicate these two isomers have different functions on rat's CNV prevention and on HUVEC cell proliferation.

Background Compare with the lamellar laser refractive surgery,the laser slip on the surface operation is a better method in the correct of refractive error without the flap-related complications.However,whether to remain corneal epithelial flap and its influence for epithelial healing and visual restoration are still under investigation.Objective The aim of this study was to compare the short-term clinical efficacy of epipolis laser insitu keratomileusis (Epi-LASIK) and flap-free Epi-LASIK for correction of refractive error in high myopia.Methods The paired control design was adopted.Sixty eyes of consecutive 30 patients with high myopia were collected in this study.The written consent form was obtained from each patients prior to operation.Regular EpiLASIK was performed in the right eyes and the flap-free Epi-LASIK was carried out in the left eyes.Patients were followed-up for one month.The postoperative ocular irritation symptoms were scored,and the healing period of corneal epithelium and uncorrected visual acuity were examined at 1,3 and 5 days after operation.The naked visual acuity,diopter,best corrected visual acuity and the grading of haze were recorded and compared between the two groups at one month after operation.Results After surgery,the scores of corneal irritation were 3.13 ±0.43 and 3.30±0.47on the first day,showing insignificant differences between these two groups (t =- 1.54,P＞0.05 ).However,there existed statistically significant difference in the scores of corneal irritation on the third day after operation between the two groups (t =- 17.95,P＜0.01 ).The average time of corneal epithelial healing were (2.58 ±0.49 ) days in the flapfree Epi-LASIK group and ( 3.98 ±0.74) days in Epi-LASIK group with the significant difference between them (t=-11.36,P＜0.01 ).There was no statistical difference in uncorrected visual acuity in the first day (0.59±0.12 vs 0.58±0.11,t=0.39,P＞0.05),the fifth day (0.69±0.08 vs 0.67±0.09,t=0.84,P＞0.05) and 1 month (t =-1.90,P＞0.05 ).No significant difference was seen in the diopter between the two groups in 1 month after surgery (-1.03±0.45 vs -1.07 ±0.38,t =-0.31,P＞0.05 ).The eye numbers of corneal haze for 0 grade were 27 ( 90.00％ ) and over the 0.5 grade were 3 ( 10.00％ ) in flap-free Epi-LASIK group respectively,and those of corneal haze for 0 grade were 26(86.66％ ) and above the 0.5 grade were 4 (13.33％) in Epi-LASIK group respectively,showing a considerably difference between the two groups (x2 =0.0031,P＞0.05).Conclusions Both the flapfree or reserved epithelial Epi-LASIK allow the safe and effective correction of refractive error in high myopia,showing good predictability and stability in short term.Flap-free Epi-LASIK can relieve the corneal irritation symptom and accelerate the healing of corneal epithelium and recovery of visual acuity.

Objective To analyse a novel splice mutation in EXT1 gene of hereditary multiple osteochondroma, and study its pathogenic mechanism.Methods In April of 2013, the proband was hospitalized from the outpatient department with multiple joint deformity for more than 20 years, peripheral blood of the proband and his parents were collected and genomic DNA was extracted .Coding regions and adjacent intron sequences of EXT1/EXT2 genes in genomic DNA of the family members were amplified and sequenced.Bioinformatics was used to analyze the mutation from sequencing .cDNA from peripheral blood of the proband ,the mother and normal control was made respectively as a template for amplifying coding regions of EXT1 gene, and the product was T-A cloned and sequenced.The abnormal transcripts of each group were counted and analyzed using chi square test to study the pathogenic mechanism of the mutation .Results Sequencing results of family members revealed that there was a heterozygous deletion mutation ( c.1284 +2del) in the 5′splice site of intron 4 in EXT1 gene of the proband and his mother .Bioinformatics predicted that exon 4 of EXT1 gene was skipping or spliced aberrantly due to the mutation .T-A clone and sequencing results as well as the statistical analysis suggested that there was a significantly higher proportion of transcripts with skipping exon 4 in the proband and his mother compared with the normal control (P=0.000, P<0.01).Conclusions c.1284+2del in EXT1 gene is reported for the first time internationally , which results in a considerable number of abnormal transcripts with skipping exon 4 in EXT1 gene, thereby influences the normal transcription and translation of EXT1 gene.

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg^-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.