The glucose-regulated protein78 (GRP78) is a member of the heat-shock protein 70 (HSP70) family and responsible for cellular homeostasis. GRP78 is highly expressed in various tumors. It plays an im-portant role in tumor proliferation, survival, metastasis, and drug resistance. Suppression of GRP78 in tumors could enhance cancer treatment. Inhibition of GRP78 in tumors may provide a noval approach toward cancer therapy.

Avellino corneal dystrophy(ACD) is an autosomal dominant eye disorder caused by mutation of R124H in the transforming growth factor-beta induced gene (TGFBI) on chromosome 5,which was responsible for accumulating of abnormal TGFBI.Although the underlying mechanism by which mutations cause abnormal TGFBI deposition is not yet clear,but we have a better understanding of the etiology and possible pathogenesis of corneal dystrophy with the rapid development of human genetics and molecular biology,and summarizes the current achievement of this disease and understand the roles of TGFBI and its interaction with Periostin,which may contribute to further research in ACD.

Objective To summarize the clinical features,diagnosis,treatment and prognosis of hepatolithiasis complicating cholangiocarcinoma. Methods From June 1958 to March 2011,709 cases of hepatolithiasis were admitted to Department of General Surgery,Peking University Third Hospital.The cases concomitant with cholangiocarcinoma were reviewed. Results 20 of 709 (2.8％ ) hepatolithiasis cases developed cholangiocarcinoma.17 cases (85％,17/20) were followed-up for 2 years (0 - 15 years).The hepatolithiasis course before the malignant diagnosis was 15 ± 1 1 years (3 -38 years).14 cases had frequent episodes of cholangitis,15 cases had liver cirrhosis.Preoperative diagnosis was established by CT,MRCP,B-ultrasound and tumor markers in 55％ (11/20) cases.4 cases underwent radical resection,7 received palliative resection,9 cases received conservative treatment.In radical resection,one lost to follow-up,one survived one year,two for 5 years.In palliative resection,2 lost to follow-up,two survived one year,one survived 3 years, one for 5 years. None in conservative group survived more than one year.Conclusions Cholangiocarcinoma developed from hepatolithiasis with a long history,frequent cholangitis,liver cirrhosis,especially in cases with imige showing thickness of bile duct or mass and rising tumor markers (CA19-9,CA125,CEA).The cases undergoing radical resection may have a favorable prognosis.

The zinc chloride and cystine resistant strain of S.cerevisiae YZM-14(ZnCl2r,Cysr) was screened with the mutant processing of the protoplast of S.cerevisiae by combinative mutagens of ultraviolet and nitrite.The glutathione(GSH) production(84.72 mg/L),dry cell weight(7.63 g/L) and the intracellular GSH content(11.10 mg/g) of YZM-14 were 2.79,1.63 and 1.71 times compared with that of the initial strain.The biosynthetic process of GSH was divided into three phases according to the time course of the specific cell growth rate and GSH yielding coefficient.In the second phase,the metabolic flux of the pentose phosphate pathway and the GSH precursors biosynthetic pathway of the mutant strain increased by 8.1 mmol/(g?h),compared with that of the initial strain.Furthermore,the metabolic flux of the organic acids secretion of the mutant strain decreased.Through these mechanisms,the utilization efficiency of the carbon sources was enhanced and high production of GSH was obtained.

AIM: To explore whether strontium ranelate ( Sr ) promotes osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) through the Hedgehog/Gli1 signaling pathway.METHODS:BMSCs were isolated from 4-week-old rats by adherent culture and induced to differentiate into osteoblasts .According to the experimental purposes , the cells were exposed to different concentrations of Sr , cyclopamine ( Cy, an inhibitor of Hedgehog receptor ) or Gli1-siR-NA.The expression of Gli1 and Runx2 in the cells was detected by Western blotting .The activity of alkaline phosphatase ( ALP) was measured by the method of colorimetry , and the mineralized nodules were observed under microscope with aliz-arin red staining .RESULTS:Exposure to Sr at concentrations of 0.1 to 5 mmol/L for 7 d markedly increased the expres-sion of Gli1 in the BMSCs , and the increase in Gli1 expression was the most obvious following Sr exposure at concentration of 3 mmol/L.Cy at concentration of 10 μmol/L inhibited Sr-induced up-regulation of Gli1 expression.Transfection of the BMSCs with Gli1-siRNA not only obviously inhibited Sr-induced up-regulation of Gli1 and Runx2 ( a downstream protein of Gli1) expression, but also antagonized Sr-induced enhancement of ALP activity and the formation of mineralized nodules . CONCLUSION:The Hedgehog/Gli1 pathway is involved in Sr-induced osteogenic differentiation of rat BMSCs .

Background The incidence of myopia is increase.Some researches documented that formation of myopia is closely related with weakness of the accommodative response,enhancement of accommodative lag and accommodative microfluctuations in short-distance use of eyes.However,there still is controversy.Objective This study sought to compare the accommodative microfluctuations among emmetropic and myopic school-aged children at reading,and to discuss its potential relationship with the onset and development of myopia.Methods A casecontrolled study was designed.Eighty-nine children aged 8-12 years old were recruited in this study,including 47emmetropic children and 42 myopic children.Refractive error were checked by subjective refraction in phoropters and binocular vision and stereopsis were examined in all the subjects.A Grand Seiko WAM5500 auto-refractor was used to measure the accommodative responses and accommodative microfluctuations with different stimulus in 40 cm and 25 cm.The differences in accommodative response and accommodative microfluctuations at 25 cm and 40 cm reading distance were compared between the emmetropic children and myopic children using independent sample t test,and change of accommodative microfluctuations in myopic children at 25 cm and 40 cm reading distance was evaluated by paired t test.Results When the reading distance was 25 cm and 40 cm,the accommodative responses of emmetropes were (2.67 ±0.31) D and (1.70 ±0.23) D,and they were higher than (2.31 ± 0.33) D and (1.49 ±0.24) D of myopes,showing significant differences (t =5.330,P =0.000; t =4.140,P =0.000).Accommodative microfluctuation of myopes was(0.35 ±0.16)D in 25 cm reading distance and that of emmtropes was(0.26±0.08)D,with significant difference between them (t =3.180,P =0.002).However,there was not significant difference in accommodative microfluctuation at 40 cm reading distance between the myopic children and emmtropie children [(0.27±0.10) D vs.(0.24±0.09) D] (P=0.220).In myopic children,the accommodative microfluctuation at 25 cm reading distance was(0.35±0.16) D,showing a much increase than(0.27±0.10) D at 40 cm reading distance(t=3.850,P =0.000),but an insignificant difference in the accommodative mierofluctuations was seen between the 25 cm and 40 cm reading distance in the emmetropic children (P =0.145).Conclusions With the increased accommodative stimulus,myopic children present lower accommodative responses and larger accommodative microfluctuations.

Objective To determine the incidence and risk factors of iatrogenic retinal breaks in eyes undergoing pars plana vit- rectomy for idiopathic macular pucker.Design Retrospective case series.Participant 88 consecutive vitrectomies performed on eyes with idiopathic macular pucker.Method Consecutive vitrectomies performed on eyes with idiopathic macular pucker at Beijing Tongren Eye Center between 2002 and 2006 were retrospectively reviewed.Cases with iatrogenic retinal breaks were recorded and analyzed. Main Outcome Measure Number and location of retinal breaks,and anatomic outcome after surgical managements.Result A total of 88 consecutive vitrectomies were included in the study.Of the 88 eyes,8 eyes had 14 iatrogenic retinal breaks detected,with an aver- age incidence of 9.1%.Peripheral retinal breaks(8.0%)were more common than posterior retinal breaks(1.1%).All peripheral retinal breaks occurred around the selerotomy sites(100%)and the quadrant of predominant hand was involved most commonly(62%).Most of the breaks(88%)were detected during the surgery.All eyes with iatrogenic retinal breaks obtained anatomic retinal reattachment (100%).Conclusion Despite improvements in instrumentation and surgical techniques,iatrogenic retinal break continues to be an im- portant complication of pars plana vitrectomy in eyes with idiopathic macular pucker.This complication tends to occur more commonly at peripheral retina and is mainly selerotomy-related.

Objective To investigate the clinicopathology and immunophenotype of primary non- Hodgkin lymphoma(NHL)of the female genital system,and to analyze the prognosis of such tumors. Methods Clinicopathologic features of 43 cases of primary NHL of the female genital system were studied retrospectively,with the histological classification based on the Classification of Haematopoietic and Lymphoid Tumors(WHO,2001).Immunochemistry technique,in-situ-hybridization and polymerase chain reaction methods were used to detect the immunophenotype,epstein barrvirus(EB)virus infection status and immunoglobulin heavy chain gene rearrangement,respectively.Results(1)Primary lesions:there were 24 cases of lymphoma originating in the ovary,3 cases in the endometrium,10 cases in the cervix,2 cases in the vagina and 4 cases in the vulva.(2)Staging:12 cases(28%)were in stage Ⅰ,9 cases (21%)in stage Ⅱ,and 22 cases(51%)in stage Ⅲ.(3)Histological classification:37 cases(86%)were diffuse large B cell lymphoma(DLBCL),3 cases were Burkitt lymphoma and the remaining 3 cases were unspecified peripheral T-cell lymphoma according to biopsy,immunophenotype analysis,in-situ- hybridization technique and IgH gene rearrangement detection.(4)Prognosis analysis:increase in the level of lactic acid dehydrogenase,stage Ⅲ,DLBCL and single operation suggest poor prognosis.Conclusions Establishment of the diagnosis of primary NHL of the female genital system is based on biopsy, immunophenotype analysis,in-situ-hybridization technique and IgH gene rearrangement detection,which play important roles in diagnosis and differential diagnosis of the tumor.Combined therapy is the first choice of therapeutic regimens.

To determine the relationship between the intercellular adhesion operon (ica) and the biofilm production in Staphylococcus epidennidis isolates from nosocomial infection, and the affection of ica on the antibiotic susceptibility of the isolates, we collected 106 strains, epidermidis isolates from nosocomial infection specimen to detect their biofilm production by quantitative and qualitative method and investigate the existence of ica operon by PCR. The minimal inhibitory concentration (MIC) to erythromycin, ampicillin, cefoxitin, ceftriaxone, teco-planin, ciprofloxacin, tetracycline, trimethoprim-sulfamethoxazole and vancomycin were tested. Among the isolates, 33 (31. 1% ) of them were detected out carrying ica operon. The rate of biofilm production of the ica-posi-tive isolates was higher than that of the ica-negative (P =0. 001) . By adding glucose and NaCl into the culture the detection rate of biofilm production could be increased. The antibiotic susceptibility of the plankton cells of ica-positive isolates to erythromycin, cefoxitin and ceftriaxone , except ampicillin, ciprofloxacin, tetracycline and tremethoprim-sulfamethoxazole, were lower than those of ica-negative isolates. This study showed that the existence of ica operon was close related to the biofilm formation in 5. epidermidis isolates from nosocomial infection. However, the mechanism of antibiotic resistance of the strains inside the biofilm still needed to be illustrated.

AIM: To investigate whether Janus kinase/signal transducer and activator of transcription ( JAK/STAT) signaling pathway mediates high glucose-induced damage in human umbilical vein endothelial cells ( HUVECs ) . METHODS:The cell viability was examined by CCK-8 assay.The expression levels of JAK2, STAT3, caspase-9 and en-dothelial nitric oxide synthase ( eNOS) were detected by Western blot .The intracellular levels of reactive oxygen species ( ROS) were tested by DCFH-DA staining followed by photofluorography .Mitochondrial membrane potential ( MMP) was measured by rhodamine 123 staining followed by photofluorography .RESULTS:Treatment of HUVECs with high glucose (40 mmol/L glucose) for 6~12 h enhanced the protein level of phosphorylated JAK 2, peaking at 9 h.Treatment of the cells with high glucose for 6~12 h also increased the protein level of p-STAT3 with the peak value at 12 h.Pretreatment with the inhibitor of JAK/STAT pathway AG490 for 1 h before exposure of the HUVECs to high glucose significantly inhibi-ted the high glucose -induced injury , as evidenced by an increase in the cell viability , decreases in the expression of caspase-9 and the intracellular ROS production , and increases in MMP and the expression of eNOS .CONCLUSION:JAK/STAT signaling pathway is involved in the high glucose-induced damage in HUVECs .