Objective To investigate the effect of artesunate on the expression of heat shock protein 47(Hsp47)in pulmonary fi-brosis in rats.Methods Thirty SD male rats were randomly divided into control group,model group and artesunate intervention group (intervention group).Rats in control group were intrachacheally instilled with saline (0.4 mL),while rats in other two groups 5 mg/kg bleomycin.Rats in both control group and model group were intraperitoneal injected with 1 mL saline per day sub-sequently.And the rats in intervented group were intraperitoneal injected with 10 mg/100 g artesunate per day.The body weight of day 0,day 14 and day 28 were recorded.All the rats were sacrificed on day 28.The pulmonary coefficient and the hydroxyproline content were observed.The expression of Hsp47mRNA and CollagenⅠmRNA were evaluated by RT-PCR.The Hsp47 expression was also detected by Western Blot.The pathological changes were analyzed by hamatoxylin-eosin (HE)stain and Masson stain.Re-sults (1)The body weight of control group grew much faster than other groups (P <0.05).(2)Pulmonary coefficient:model group (12.31±1.89)mg/g>intervention group (8.54±0.67)mg/g>control group(4.81±0.38)mg/g (P <0.05).(3)Ashcroft Scores:model group(5.70±1.09 )>control group (3.08±0.56),model group(5.70± 1.09)>intervention group (4.01 ± 1.25).There was no significant difference between control group and intervention group(P >0.05).(4)Hydroxyproline content:model group (620.33±66.16)μg/g>control group(379.00±35.51)μg/g,model group (620.33±66.16)μg/g >intervention group(429.00± 36.51)μg/g (P <0.05),there was no significant difference between control group and intervention group.(5)Hsp47mRNA expres-sion:model group and intervention group > control group (P <0.05),there was no difference between the first two groups(P >0.05).CollagenⅠmRNA:model group > intervention group>control group (P <0.05).(6)Western blot showed that Hsp47 ex-pression of model group was the highest in all three groups.Conclusion These results indicate that artesunate might inhibit pulmo-nary fibrosis and depress CollagenⅠproduction,and it′s probably a result of Hsp47 down regulation.

Objective To investigate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) in the treatment of oral ulcer caused by chemotherapy.Methods 108 patients of oral ulcer caused by chemotherapy were randomly divided into two groups.54 cases in the control group were treated with cydiodine buccal tablets at first,then received the aerosol treatment which was prepared by mixing gentamicin,dexamethasone,2 ％ lidocaine and physiologic saline,three times per day.54 cases in the treatment group firstly received the gargle which was prepared by mixing rhGM-CSF,dexamethasone and physiologic saline,then were treated with rb-bFGF by spraying on the oral ulcer surface,three times per day.Results The effective rate of the treatment group was 96.30 ％ (52/54),which was significantly higher than that of the control group [64.81％ (35/54)],there was a significant difference between the two groups (x2 =17.08,P ＜ 0.05).Conclusion The effect of rhGM-CSF combined with rb-bFGF in the treatment of oral ulcer caused by chemotherapy is very significant.

This study is to investigate the effect of artesunate on transforming growth factor-beta1 (TGF-beta1) induced epithelial-mesenchymal transition (EMT) and its possible mechanism. After the in vitro cultured RLE-6TN cells were treated with TGF-beta1 then artesunate intervened on it, after 24 h, expression of the markers of mesenchymal cell was assayed using Western blotting and real-time PCR analysis. Western blotting was also used to detect the effect of TGF-beta1 on the Smad3 and Smad7 expressions of RLE-6TN cells. Morphological alterations were examined by phase-contrast microscope, and ultrastructure changes by electron microscope. Incubation of RLE-6TN cells with TGF-beta1 resulted in the up-regulation of the expression of the mesenchymal cell markers, after artesunate intervened on it, resulted in the down-regulation of the expression. Meanwhile, incubation with artesunate intervened on RLE-6TN cells could lead to the apparent down-regulation of the expression of Smad3 and up-regulation of Samd7 and the transition of RLE-6TN cells to mesenchymal-like by TGF-beta1 induction, after artesunate intervened on it, RLE-6TN cells to epithelial-like. TGF-beta1 induced epithelial-mesenchymal transition process; artesunate can inhibit TGF-beta1-induced epithelial-mesenchymal transition process, the possible mechanism is up-regulation of the expression of Smad7 and down-regulation of the expression of Smad3, meanwhile inhibits phosphorylation of Smad3.

Objective To explore the therapeutic effects and adverse reactions of thalidomide in the treatment of peri-chemotherapy nausea and vomiting of cancer patients.Methods Total of 70 patients were randomly divided into two groups:the treatment group (38 cases) and the control group (32 cases).The treatment group was treated with thalidomide (oral administration at a dose of 100 mg per night,then dose can be added by 50 mg until the top dose of 200 mg per day).The original will be maintained if they cannot be tolerate of extensive dose.The treatment group was also injected 2mg tropisetron in 30 minutes before chemotherapy.The control group was only injected same dose tropisetron.All cases were examined antiemetic effects and evaluated adverse reactions.Results Nausea and vomiting control rates were 89.5 ％ (34/38) and 68.8 ％ (22/32) respectively in the treatment group and control group respectively with significant difference.The adverse reactions were similar between the two groups.Conclusion Thalidomide joint tropisetron can effectively control the peri-chemotherapy nausea and vomiting,and the adverse reactions can be acceptable.It could improve further indications of the drug.

BACKGROUND:Heat Induction Typodont System (HITS) and Double-Slot Lingual Bracket System are patented products of the research group.It is very important to explore a good control of anterior tooth torque on the micro-implant-double-slot lingual bracket system.OBJECTIVE:To provide the experimental basis for force system applied for controlling the anterior tooth torque in lingual orthodontics through Typodont experiment based on the HITS.METHODS:Sixteen Class Ⅱ1 maxillary Typodont models without first premolar were made.Micro-implants were implanted in the lingual region of posterior teeth and labial region of anterior teeth.The direction of the retracting force was adjusted by changing the position of the lingual micro-implant (with a distance of 4,8 mm from the alveolar crest) and the length of the hook (4,8 mm).And lingual retracting force (150,300 g) and labial intruding force (50,100 g) were loaded.The tooth movement by HITS was simulated and the models were scanned before and after force loading.Then the three-dimensional images were reconstructed by Mimics 17.0.Factorial variance analysis was adopted to compare the anterior movement changes under different loading modes.RESULTS AND CONCLUSION:When the length of the hook was 4 mm/8 mm and the lingual micro-implant was 6 mm/10 mm from the alveolar crest,the displacement difference between the incisal edge and the root of the anterior teeth was smaller than other groups.The optimal mechanics was 150 g for the lingual retracting force and 100 g for the labial intruding force.It could provide a satisfactory control to the anterior teeth torque when retracting force and labial intruding force were loaded at the same time during the space closing phase of lingual treatment.This study based on HITS provided a scientific basis for the clinical application of micro-implant-double-slot lingual bracket system in space closing phase.

Objective To understand the clinical epidemiology of nosocomial candidemia in Huashan Hospital during a 10-year period. Methods One hundred and nine cases of nosocomial candidemia in Huashan Hospital affiliated Fudan University during the period of 1998- 2007 were retrospectively reviewed. The underlying conditions, risk factors, clinical manifestations, treatment and outcome were described. The prognostic factors were analyzed by chi square test or Fisher exact probability test. Multivariate analysis was done by multiple Logistic regression. Results The average annual incidence of nosocomial candidemia during the study period was 0.28/10 000 patients per day.The most common pathogen was C. albicans (59/109,54.1%), followed by C. tropicalis (20/109,18.3%), then C. parapsilosis (11/109, 10. 1%), C. glabrata (11/109, 10.1%), and other Candida spp. (8/109, 7.3% ). Underlying diseases frequently identified included diabetes (50,45.9%), solid malignancy (32, 29.4%), head trauma (13, 11. 9%) and stroke (12, 11.0%).There were 37 cases who died or deteriorated. The overall mortality was 34.0% and the attributable mortality was 22. 0% (24/109). In multivariate prognostic analysis, retention of central venous catheters (OR: 5.42, 95% CI: 1.68-17.41, P＝0.005), corticosteroid medication (OR: 3.69,95% CI: 1.10-12.34, P=0. 034), and severe sepsis on the day of candidemia (OR: 2.94, 95% CI:1.72-15. 21, P = 0. 003) were factors independently correlated to increased mortality. Furthermore,adequate antifungal therapy was the only independent predictor of decreased overall mortality (OR: 0. 27,95% CI: 0. 09-0. 78,P=0.015). Conclusions The incidence of nosocomial candidemia in our hospital has been increasing during the past decade. Timely diagnosis and treatment plays a key role in the management of nosocomial candidemia,

Objective To describe the distributions of FCGR polymorphisms in human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis,and to investigate the association of FCGR polymorphisms with the susceptibility to cryptococcosis.Methods The distributions of the four functional polymorphisms,including FCGR2A 131H/R,FCGR3A 158F/V,FCGR3B NA1/NA2,and FCGR2B 232I/T were compared between 198 cryptococcosis patients and 190 healthy controls.The polymorphisms distribution patterns were also compared between patients with central nervous system (CNS) infection and those without CNS infection.Genotyping of eight single nucleotide polymorphism (SNP) in FCGR were performed by multiplex SNaPshot technology using DNA extracted from blood samples.The comparison between patients and controls was performed by chi square test or Fisher exact test.Results Compared to healthy controls,the frequency of FCGR2B 232I/I increased (65％ vs 53％,x2 =4.27,P=0.039,OR=1.652,95％CI:1.02-2.67) and that of FCGR2B 232I/T decreased (27％ vs 40％,x2 =5.77,P=0.016.OR=0.542,95％CI:0.33-0.90) in patients with cryptococcal meningitis.Among immunocompetent patients,the frequency of FCGR2B 232I/I was also over-presented (69％ vs 53％,x2=4.53,P =0.033,OR=1.958,95％CI:1.05-3.66) and the FCGR2B 232I/T genotype was also less frequently observed (24％ vs 40％,x2=5.14,P=0.023,OR=0.467,95％CI:0.24-0.91) compared to healthy controls.There were 117 cases with CNS infection and 81 non-CNS infection cases.The genotype of FCGR2A 131R/Rwas over-presented (19％ vs 6％,x2 =6.48,P=0.011,OR=3.52,95％CI:1.27-9.73) and the FCGR2B 232I/T genotype was under-presented (27 ％ vs 46 ％,x2 =7.56,P =0.006,OR=0.431,95％CI:0.24-0.79) in patients with CNS infection compared with those without CNS infection.Furthermore,the frequency of FCGR2B 232I/I genotypes increased (69％ vs47％,x2 =5.47,P=0.019,OR=2.479,95％CI:1.15-5.34) and the frequency of FCGR2B 232I/T decreased (24％ vs 51％,x2 =8.66,P=0.003,OR=0.307,95％CI:0.14-0.68) in immunocompetent patients with CNS infection compared with those without CNS infection.Conclusions FCGR2A 131H/R and FCGR2B 232I/T are associated with the susceptibility to cryptococcal CNS infection,which suggests that FcγRⅡA and FcγRⅡB may contribute to the pathogenesis of cryptococcosis.

Aim To provide references for clinical trials dose and rational drug use by evaluating mitochondrial toxicity of bentysrepinine on HepG2 cells.Methods Mitochondrial toxicity of bentysrepinine on HepG2 cells was cmomprehensively evaluated by measuring proliferation inhibition rate, lactic acid content in culture supernatant, reactive oxygen species(ROS) content, mitochondrial membrane potential (MMP) variation and the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅳ.Results The half inhibitory concentration of bentysrepinine of HepG2 cells was 359 μmol·L-1.Compared with the control group, bentysrepinine could reduce the MMP, raise the level of lactic acid, increase the content of ROS and lower the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅲ with the concentration of 400 μmol·L-1(196 mg·L-1), showing an obvious mitochondrial toxicity.Compared with lamivudine and adefovir dipivoxil, bentysrepinine exerted no influence on indexes above with the same concentration 100 μmol·L-1.Conclusions Bentysrepinine shows an obvious mitochondrial toxicity on HepG2 cells with the concentration of 400 μmol·L-1.This mitochondrial toxicity is not presented with the concentration of 200 μmol·L-1.It shows that the safety range of bentysrepinine about mitochondrial toxicity is relatively wide.The test plays a guiding role in clinical trial dose design as well as clinical treatment.

Objective To analyze the clinical features of patients with uncommon fungal infections in central nervous system (CNS).Methods Thirty-five patients with uncommon CNS fungal infections who were admitted to Huashan Hospital from 1997 to 2010 were retrospectively reviewed.The pathogens,symptoms and signs.treatments of patients were evaluated.The data were analyzed by rank sum test and Fisher'S exact test.Results Twenty-nine of the 35 patients met the definition criteria of prover CNS fungal infections,while the other 6 had probable diagnosis.Predisposing factors were found in 86% of all patients.The most common pathogens were Aspergillus and Candida species.The symptoms and signs commonly occurred including fever(22 cases),headache(19 cases), cranial neuropathy(12 cases),and meningeal irritation sign(12 cases).High white blood cell count,high protein level,and low glucose level were the main findings of cerebrospinal fluid (CSF) analysis.Patients with cerebral aspergillosis were more frequently accompanied with immunocompromised conditions, and they often got CNS aspergillosis from hematogenous dissemination or direct extension of paranasal sinus infection.Cerebral granuloma and abscess were the common clinical characteristics of CNS aspergillosis.Cerebral candidiasis often arose from neurosurgical surgery or traumatic brain injury,and these patients were usually presented with meningitis.All patients were treated with antifungal drugs and (or) surgical intervention and 77%(27/35) of the patients achieved complete or partial responses. Antifungal agents combined with surgical resection might improve outcome of patients with CNS aspergillosis; while removal or replacement of drainage tubes in combination with antifungal treatment showed satisfactory efficacy in patients with cerebral candidiasis who usually had shunt manipulation. Conclusions The incidence of CNS fungal infection, such as cerebral aspergillosis and candidiasis, is increasing. Early diagnose and therapeutic intervention are crucial for improving outcome.

Objective To describe the distribution of mannose binding lectin (MBL) genetic polymorphisms in non-acquired immunodeficiency syndrome (AIDS) patients with cryptococcosis in China and to verify the association of MBL polymorphisms with susceptibility to cryptococcosis.Methods The case-controlled genetic association study was conducted and 167 non-AIDS patients with cryptococcosis and 208 healthy controls were recruited. Genome DNA was extracted from the peripheral blood and MBL gene was amplified by polymerase chain reaction (PCR). Six singlenucleotide polymorphisms ( SNP) of MBL gene were sequenced. The association of MBL polymorphisms with susceptibility to cryptococcosis were analyzed. The comparison between patients and controls was performed by chi square test or Fisher's exact test. The differences of MBL plasma concentrations between groups with different MBL genotypes were compared by single factor variance analysis. Results There were no differences between patients and controls in terms of MBL genotype frequencies, haplotypes and genotypes (all P>0. 05). Compared with healthy control, the deficient MBL-producing genotypes were strongly associated with cryptococcal meningitis (16. 5% vs 8. 7%,χ2=4.25, P=0.0392, OR = 2.09), particularly in patients without underlying immunocompromised conditions (21. 4% vs 8. 7%, χ2 =7. 15, P = 0. 0075, OR = 2. 88). Individuals with MBL deficiency genotypes showed significantly higher rates of central nervous system (CNS) cryptococcal infection rather than non-CNS cryptococcosis (16. 5% vs 3. 1%, Fisher's exact test, P = 0. 010, OR = 6. 13).The difference was even more significant in the immunocompetent patients (21. 4% vs 4. 0%, P =0.009, OR= 6. 55). Conclusion MBL deficiency is associated with cryptococcal meningitis and may play a role in CNS Cryptococcus infection.