BackgroundDry eye is a multi-factorial-induced tear film and ocular surface disorder.Immunoinflammation plays a key role in the pathogenesis of dry eye.As inhibitor of the cyclo-oxygenase pathway,nonsteroidal anti-inflammatory drugs play an anti-inflammatory and anti-hypersensitivity role,and it can be a potential treatment for dry eyes.ObjectiveThis study was to investigate the effectiveness of nonsteroidal anti-inflammatory drugs (0.1％topical pranoprofen) on moderate to severe dry eyes and its mechanism.MethodsThis was a small sample of randomized controlled clinical trial.Thirty right eyes of 30 patients with moderate to severe dry eyes were included in the study according to the diagnosis criteria and randomized into two groups.The patients of the trial group received topical administration of 0.1％ pranoprofen plus 0.1％ sodium hyaluronate,and those of the control group received the topical 0.1％ sodium hyaluronate only.Ocular surface inflammation index scores (OSDI) and ocular surface fluorescine staining (OSS) scores were measured under the slit lamp,and tear film break-up time (BUT),Schirmer Ⅰ test values were evaluated.The expression of human leucocyte antigen-DR (HLA-DR) and CD11b in conjunctiva epithelial cells were detected by impression cytology and flow cytometry (FCM).All the indexes were compared between the two groups before and after treatment.Informed consent was obtained from all patients.ResultsThere were no significant differences in terms of age and gender and their baseline values between the trial group and control group (t=0.412,P=0.684;x2=0.240,P=0.624),and so were all the indexes (P＞0.05).Compared with the control group,the OSDI,OSS scores and cells positive for HLA-DR were lowered but the BUT was delayed in the trial group on day 15 ( t=2.43,P=0.03;t=2.83,P=0.01;t=3.29,P=0.00;t=3.23,P=0.00 ).No significant differences were found in the Schirmer Ⅰ test value and CD11b expression between these two groups (t=0.17,P=0.87;t=0.28,P=0.79).The OSDI,OSS scores and BUT were significantly improved,and the number of cells positive for HLA-DR were reduced 15 days after administration of drugs in comparison with before treatment in the trial group ( t =12.30,10.70,6.10,7.92,P =0.00 ).However,there were no comparable alteration seen in these indexes before and after the usage of drugs in the control group ( P＞0.05).Positive correlations were found in HLADR expression with OSDI and OSS ( r =0.601,P =0.018 ; r =0.586,P =0.022 ) and a negative correlation in HLADR expression with BUT (r=-0.697,P=0.004) on day 15 in the trial group.ConclusionsTopical usage of 0.1％ pranoprofen is beneficial for remitting the ocular signs and symptoms in moderate to severe dry eyes.This study illustrates that topical usage of 0.1％ pranoprofen can down-regulate the expression of inflammatory markers in conjunctival epithelial cells.

Objective To study the sources and the relationship between the management and the outcome of hemorrhage after cephalic pancreatoduodenectomy.Methods The clinical data of 370 patients who underwent pancreatic resection at the Lihuili Hospital and the Second Affiliated Hospital of Zhejiang University were retrospectively analyzed.Results Postoperative bleeding occurred in 35 patients with 11 deaths.Among those intraabominal bleeding occurred in 14 cases and gastrointestinal hemorrhage occurred in 22,with one case suffering from both.Bleediug developing within 72 hours after operation in 12 cases (early-stage group),which was caused by improper intraoperative homeostasis.In other 23 cases,bleeding 72 hours after operation(later stage group)was caused by the erosion following pancreatic and/or bile leakage.Relaparotomy was performed in 13 cases and endoscopic homeostasis was performed in 3. Relaparotomy or endoscopic homeostasis was superior to that of conservative therapy in the early-stage group (P0.05).Pancreatic or bile leakage was identified as the significant risk factors for the postoperative bleeding.Conclusions In order to prevent the postoperative hemorrhage and to reduce the mortality of pancreatic resection,skillful techniques,expeditious homeostasis,proper management of stump pancreas and the prevention of pancreatic and bile leakage are essential.

The expression cDNA library of A. tabescens was constructed by SMART technique, which useλTriplEx2 as a vector. The titer and the percentage of the constructed library were about 1.0 × 106pfu/mland 98.3% respectively, and the titer and the capacity of the amplified library were about 3.1 × 108pfu/mland 4.2 × 1010. The library was used to provide expressed sequence tags (ESTs). 147 Expressed SequenceTaqs (ESTs) were gained from 176 clones, which were selected randomly and sequenced at the 5'end. Thesequences were submitted to the EMBL database. Blasting the sequences in the GenBank, 43 of them werefound that they have significant similarity with data in GenBank. EST AJ620046 was has significantsimilarity with the arabinosidase of Bacteroides thetaiotaomicron. Using SMART-RACE a full-length cDNA ofAJ620046 was successfully obtained. In order to initially characterize the biochemical properties ofAJ620046, the ORF of AJ620046 named AF was cloned and expressed in Pichia Pastoris yeast.Recombinant pHIL-S1-AF constructed by inserting AF into pHIL-S1 was transformed into Pichia PastorisGS115. Preliminary experiments indicated that AJ620046 was expressed as a 32 kDa protein in recombinantyeast.

Signal transducer and activator of transcription (STAT) 3 is a critical transcription factor for cell proliferation and survival. It is activated within cells by many cytokines to mediate immune and inflammatory responses to injury. Inflammatory bowel disease (IBD), represented by Crohn′s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the intestinal tract. STAT3 has been shown to be abnormally activated in IBD colon tissues by many pro-inflammatory cytokines, leading to disruption of the intestinal mucosal barrier and excessive innate immune and Th17 responses. The persistent chronic inflammation eventually leads to intestinal fibrosis and stenosis. In addition to immune responses, STAT3 is also involved in intestinal fibrosis in IBD by promoting the transcription of fibrosis-related genes. Colitis-associated cancer (CAC) is a particularly aggressive subtype of colorectal cancer and is associated with chronic inflammation-induced IBD. STAT3 has also been associated with CAC initiation and development. STAT3 is overactivated in tumors, which leads to suppression of the anti-tumor activity of immune cells and promotion of cancer cell proliferation, tumor angiogenesis, invasion, and migration. In the present article, we summarize the role of STAT3 in IBD and CAC and the research progress of the related drugs developed for UC and CAC treatment.

Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy.The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with epigenetic reprogramming.The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss (EPL).Embryonic villi were collected from normal pregnant women (control) experiencing medical abortion and from EPL patients at gestation ages of 6,7 and 8 weeks.The mRNAs of TET family were analysed using quantitative polymerase chain reaction (qPCR),and TET proteins using Western blotting and immunohistochemical analysis.The MethylFlashTM Kit was used to quantify the absolute amount of 5-methylcytosine (5-mC) and 5-hmC.Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age.Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples,which was consistent with the qPCR and Western blot results.The expression of TET1,TET2,and TET3 was lower in the villi in EPL group than in normal pregnancy group (P＜0.05 for all).It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo.The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL.

BACKGROUNDCyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia, hypoxia, and others lead to infant morbidity and mortality more than acyanotic heart disease does. Despite the great effort of medical research, their genetic link and underlying microRNAs molecular mechanisms remain obscure. In this study, we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.

METHODSCyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding. Four weeks later, hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals. We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization. Furthermore, we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.

RESULTSAfter surgical procedure 4 weeks later, the cyanotic model produced lower arterial oxygen tension, arterial oxygen saturation, and higher arterial carbon dioxide tension, hematocrit and hemoglobin concentration than controls (all P < 0.05). In 1273 miRNAs expressed in the immature piglets lungs, 2 most abundant microRNAs (miR-370 and miR-320) demonstrated significant difference between cyanotic and control group (all P < 0.05).

CONCLUSIONOur results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.

Animals ; Chronic Disease ; Cyanosis ; genetics ; physiopathology ; Gene Expression Profiling ; Heart Atria ; surgery ; MicroRNAs ; analysis ; physiology ; Pulmonary Artery ; surgery ; Pulmonary Circulation ; Real-Time Polymerase Chain Reaction ; Swine ; Swine, Miniature

OBJECTIVETo examine the effect of exposure to extremely low-frequency electromagnetic fields (ELF EMFs) on the liver function of workers.

METHODSThe workers in a factory were selected as subjects, and the recent physical examination data of these workers were collected. The workers aged 20∼40 years and with more than 2 years' working experience were included for analysis; considering the intensity of electromagnetic field, the workers exposed to less electromagnetic radiation were assigned to exposure I group (n = 123), those exposed to more electromagnetic radiation to exposure II group (n = 229), and those not exposed to electromagnetic radiation to control group (n = 212). There were no significant differences in sex, age, height, and body weight between the three groups (P > 0.05). Physical examination, including measurements of direct bilirubin (DBil), alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), and albumin, was performed in a health examination center. The intensity of electromagnetic field was measured by EFA-300 power frequency electromagnetic field analyzer, and the intensity of noise by AWA5610D integrating sound level meter.

RESULTSThe intensities of electric field and the magnetic field in exposure II group were significantly higher than those in the exposure I group. The levels of ALT, ALP, AST, GGT and albumin in exposure II group were significantly higher than those in exposure I group and control group. However, the level of direct bilirubin in exposure II group was significantly lower than that in exposure I group and control group.

CONCLUSIONOccupational exposure to ELF EMFs may affect human liver function.

Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Electromagnetic Fields ; adverse effects ; Female ; Humans ; Liver ; physiopathology ; Male ; Occupational Exposure ; adverse effects ; Young Adult

Animals ; Global Health ; History, 20th Century ; Humans ; Influenza A virus ; genetics ; isolation & purification ; Influenza, Human ; epidemiology ; history ; mortality ; virology ; Orthomyxoviridae Infections ; epidemiology ; veterinary ; virology ; Swine ; Swine Diseases ; epidemiology ; virology

BACKGROUNDOssification of the posterior longitudinal ligament (OPLL) has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 (BMP2) and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2.

METHODSOPLL patients (n = 192) and non-OPLL controls (n = 304) were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3 (-726) T/C and 3 (-583) A/G in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects.

RESULTSThere was no statistical difference between the occurrence of exons 3 (-726) T/C and 3 (-583) A/G and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3 (-726) T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3 (-726) T/C and 3 (-583) A/G with number of ossified cervical vertebrae in OPLL patients.

CONCLUSIONSExon 3 (-583) A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3 (-726) T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.

Asian Continental Ancestry Group ; genetics ; Bone Morphogenetic Protein 2 ; genetics ; China ; Exons ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Neck ; Ossification of Posterior Longitudinal Ligament ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.

METHODCocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.

RESULTCompared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).

CONCLUSIONBerberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.

Berberine ; pharmacology ; Chlorzoxazone ; pharmacokinetics ; Cytochrome P-450 Enzyme Inhibitors ; Dextromethorphan ; pharmacokinetics ; Dose-Response Relationship, Drug ; Humans ; Microsomes, Liver ; enzymology ; Midazolam ; pharmacokinetics ; Phenacetin ; pharmacokinetics ; Tolbutamide ; pharmacokinetics