[Objective]Giant cell tumor of bone is notorious for its local aggressive behavior and its tendency to recur after operative treatment.Bisphosphonates is the drug of anti-osteoporosis.It is found also have anti-cancer effect recently.We conducted experiment examing the effect of bisphosphonates alendronate on the growth and survival of the cells.To study if bisphosphonates are capable of inducing cells death and significantly inhibiting their growth in vitro.[Method]Cells viability was detected by MTT Assay after the tumor cells were cured with different concentration and different time.Tumor cells apoptosis with in situ TUNEL assay and flow cytometry was detected.The active Caspase-3 was also detected.[Result]After exposure to alendronate,the cells exhibited the characteristic features of cell shrinkage,rounding and partial detachment,and demonstrated the lobulated appearance of apoptotic cells.It was much more prominent while the treating time prolonged or the concentration increased.Alendronate((5 200) M) treatment for 24 h,resulted in 2.79%~31.17% decrease in cell viability,and 11.13%~49.94% for 72 h,respectively.A significant dose-dependent and time-dependent decrease in the number of viable cells was observed in the GCT cells.After Alendronate treat for 24 h,the mean cell population in apoptosis was 14.32% at concentration 5 mmol/l,and 40.24% at 200 mmol/l.It was up to 18.41% and 42.22% respectively after 48 h.In Alendronate-treated GCT cells,Caspase-3 activation was observed.The cell response varied with doses of Alendronate showing the levels of Caspase-3 expression with a dose dependent response.[Conclusion]In conclusion,we demonstrated that bisphosphonate alendronate could inhibit GCT cells in the present study.This response was time-dependent and dose-dependent.Alendronate inducing apoptosis in GCT cells is mediated by the activation of Caspase-3.

Objective:To study the effect of Fragmin in treatment of unstable angina (UA).Methods:100 patients with UA were randomized into treatment group and control group.In the control group,the subjects were given routine drugs such as sorbitrate,nifedipine and aspirin,while those in the treatment group given fragmine in addition to the routine drugs.Results:The response rates in the treatment and control groups were 82.1% and 54.5%,respectively (P＜0.01).The total effective rates in the treatment and control groups were 92.9% and 63.6%,respectively (P＜0.01).The total effective rate of EKG improvement in the treatment and control groups were 80.4% and 50.0%,respectively (P＜0.01).Conclusion:Fragmin is effective in the treatment of UA.

Objective To summarize the clinical characteristics of patients with connective tissue diseases (CTD) and autonomic neuropathy. Methods The medical records of inpatients with CTD and autonomic neuropathy from 2005 to 2015 were retrospectively analyzed including clinical manifestations, laboratory examinations, treatment and outcome. Categorical data were expressed in percentages. Kolmogorov-Smirnov test was used to examine normal distribution. Continuous data of normal distribution were expressed as x ±s deviation, while data without a normal distribution were described as median and interquartile range (P25, P75). Results Among the nine patients included in this study, all were female, and the median age was 42 years (32~50 years old). Four patients (4/9) were systemic lupus erythematosus (SLE), three patients (3/9) were primary Sj?gren's syndrome (pSS), two patients (2/9) were rheumatic arthritis (RA), and four patients were secondary Sj?gren's syndrome (SS) (two with SLE and two with RA). Five patients (5/9) had autonomic nervous dysfunction before they were diagnosed of CTD, while four patients (4/9) developed autonomic nervous dysfunction after diagnosis of CTD. The most common symptom of autonomic nervous dysfunction was postural hypotension (9 patients, 9/9), followed by hypohidrosis (4 patients, 4/9), urinary retention (2 patients, 2/9), gastrointestinal dysmotility (2 patients, 2/9) and tonic pupil (1 patient, 11%). After treatment of CTD, autonomic symptoms of three patients improved, while the others didn't. Four of the remaining 6 patients improved after receiving other assistant treatments including vasoconstrictor, pyri-dostigmine bromide, and plasma exchange. Conclusion Patients with CTD could present with autonomic neuropathy, which is mainly characterized with postural hypotension. If patients had related symptoms, clinicians should pay more attention to whether CTD exists. If treatment for CTD couldn't improve patients' condition, other assistant treatment might be considered.

Objective To explore the influencing factor of duration of untreated psychosis(DUP) and the relationship between duration of untreated psychosis and treatment outcome in epidemiological first-episode schizophrenia. Methods 912 medical records of the first episode schizophrenia patients were recruited in the study for epidemiological survey . The general medical data, clinical diagnosis, and treatment outcome were collected. DUP was determined refer to symptom onset for schizophrenia (SOS) scale. Patients were divided into short DUP and long DUP groups according to the median values of DUP values. Results Between short DUP and long DUP groups, the difference in marriage was significant ( P < 0. 05). The unmarried patients in the short DUP group (63.7% ) was higher than the long DUP group (52.6% ), the variance was significant (λ2 =5.990, P<0.05). The divorce in the short DUP group (0.6% ) was lower than the long DUP group (4.4% ) , the variance was significant (λ2 =5.079, P<0.01).The simple schizophrenia in the short DUP group (1.5%) was lower than the long DUP group (4. 1% ) , the variance was significant (λ2 =5.868, P<0.05). The treatment outcomes between the two groups had a significant variance ( λ2 =36.093, P < 0.01) , and the Ridit analysis of treatment outcomes between the two groups showed significant difference ( u = 5.183, P<0.01). The marriage,age of onset and clinical diagnosis were significantly correlated with DUP in multiple factor Logistic regression analysis. Conclusion The marriage,age of onset and clinical diagnosis are significantly correlated with DUP in the first episode schizophrenia patients,the longer of DUP and the worse of treatment outcome.

Objective To determine the prevalence of VTE in wegener's granulomatosis(WG)and its relation with disease activity as well as the risk factors.Methods Patients diagnosed with WG between 2000 and 2008 were included.Retrospective,systematic analysis and comparison were made between the characteristics of patients in the venous thromboembolism(VTE)group and non-VTE group.Results Seyenty-onepatients with WG were included.Seven VTEs(2 pulmonary emboli.5 deep venous thromboses)occurred in association with WG,all occurred during active phase of the disease.The prevalence of VTE was 9.8%.According to univariate analysis,male sex,nephritic range proteinuria(24 h)≥3.0 g and elevated serum creatinine were significantly associated with VTE.There were no significant differences in classic risk factors between patients with and without WG-associated VTE.Conclusion Patients with WG have an increased risk of developing VTEs.especially when WG is active.Male sex,nephritic range proteinuria(24 h)≥3.0 g and elevated sernm creatinine are risk factors.Clinicians taking care of patients with WG should be highly aware of the risks for VTE and maintain a low threshold for evaluating patients for possible deep venous thrombosis or pulmonary embolism.

Objective To investigate the clinical features of 100 cases with Wegener's granulomatosis (WG). Methods One hundred patients with WG admitted to our center in recent 11 years were retrospectively analyzed. Results The ratio of male to female was 1.04:1. The average age was (39±17) years (ranging from 4 to 72 years). The upper respiratory tract (86%), lung (82%), kidney (70%) and ocular (53%) were the major affected organs, followed by neurological system ( 12% ) and cardiovascular system ( 11% ). cANCA was positive in 77% of patients, while ANCA was negative in 8%. Images mostly showed multiple nodules/mass with/without cavity in lung (59%) and sinusitis (57%). The pathologic features were necrotic granulomatosis and/or microvasculitis,which was 78% in nasal mucosa/mass biopsy and 75% in lung.Focal segmental necrotic glomerulonephritis ( 59% ) was an important feature for confirming the diagnosis. Of the WG groups, 49% of patients were in generalized subgroup followed by localized (22%), early systemic ( 15% ), severe renal (9%) and refractory group (5%). The patients were treated with corticosteroid and cyclophosphamide. The remission rate in the induction phase was 78%, while the mortality rate was 4%. The follow-up duration ranged from 1 to 145 months. Complications included infection (22%), chronic renal failure( 12% ), deep venous thrombosis( 11% ). Five patients died(8% ), in which 2 patients died of infection.Conclusion The clinical manifestations of Wegener's granulomatosis are complicate. ANCA testing, images of sinus and lung and histological biopsy have played important roles in early diagnosis, which is significant to initiate appropriate and prompt treatment in order to reduce complications and improve prognosis.

Background Our previous study demonstrated that microglial activation is closely associated with photoreceptor apoptosis in rd mice.Recent studies on central nervous system (CNS) showed that activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a key role in the microglia activation and neural cell death.However,the mechanism of NADPH oxidase during the retinal degeneration and the effect of NADPH oxidase inhibitor on photoreceptor apoptosis are concerned.Objective The aim of this study was to further explore the production of reactive oxygen species (ROS) by NADPH oxidase in the retinal degenerative process of rd mice and protection of NADPH oxidase inhibitor on photoreceptors.Methods Sixty rd mice at postnatal day 9 (P9) were randomized into the experimental group and the control group by throwing coins method.Apocynin,a NADPH oxidase inhibitor,was intraperitoneally injected in the dose of 10 mg/kg (0.01 ml/kg) once daily for 5 days (P13) in the experimental group,and the equal amount of PBS was used in the same way in the control group,and 10 C57BL/6N mice without injection of any drugs served as the wild type mice group.All the mice were sacrificed in P14 for the preparation of retinal sections.The expression of ROS in the retina was detected by dihydroethidium (DHE) fluorescence staining.Expression level of rhodopsin mRNA in the photoreceptor of the mice was determined by real-time PCR,and the thickness of retinal outer nuclear layer (ONL) in the mice of the experimental group and the control group was measured using hematoxylin & eosin staining.The use and care of the animals complied with the Statement of Association for Research in Vision and Ophthalmology.Results DHE staining showed that the ROS presented with the red fluorescence in the mouse retinas.In the rd mice of the experimental group,the ROS fluorescence intensity was dramatically enhanced in comparison with C57BL/6N mice,but weakened in comparison with the rd mice of the control group.Real-time PCR revealed that the relative expressing level of rhodopsin mRNA in the photoreceptor was (4.21±0.33) in the experimental group and (0.93±0.24) in the control group,showing a significant difference between them (t =2.360,P =0.000).The thickness value of retinal ONL was (35.95±1.63)μm in the mice of the experimental group,which was significantly higher than that in the mice of the control group ([23.17±1.38] μm) (t=3.850,P=0.016).Conclusions In the retinal degeneration of rd mice,activation of NADPH oxidase increases the ROS production.Apocynin can slow the apoptosis procedure of photoreceptor cells of rd mice.

Objective To investigate the chemical constituents of Wedelia trilobata.Methods The chemical constituents were separated by chromatography and their structures were determined by physico-chemical constants and spectral analyses.Results Eleven compounds were isolated and identified as grandiflorenic acid(1),1?-acetoxy-6?,9?-dihydroxy-4,10?-dimethyl-5?H,7?H,8?H-endesm-3-en-8,12-olide(2),1?-acetoxy-4?-hydroxy-6?-isobutyryloxy-9?-isovaleryloxyprostatolide(3),16?-hydroxy-ent-kauran-19-oic acid(4),(3R,4R,6R)-3,4-dihydroxy-1-menthene(5),trilobolide-6-O-isobutyrate(6),1?-acetoxy-4?,9?-dihydroxy-6?-isobutyroxyprostatolide(7),16?,17-dihydroxy-ent-kauran-19-oic acid(8),daucosterol(9),protocatechualdehyde(10),and caffeic acid(11).Conclusion All the compounds are isolated from W.trilobata for the first time except compounds 6 and 7.Compounds 2 and 3 are new sesquiterpene lactones,named as trilobolide A and 1?-acetoxy-4?-hydroxy-6?-isobutyryloxy-9?-isovaleryloxyprostatolide,respectively.

Objective To detect the expression of HERG (human ether-à-go-go-related gene ) potassium channel in human osteosarcoma,and explore the effects of silencing HERG by small interfering RNA (siRNA)on the proliferation and apoptosis of osteosarcoma cells and the mechanisms responsible for HERG regulation.Methods The expressions of HERG in osteosarcoma MG-63 cells and tissues were detected by reverse transcription polymerase chain reaction (RT-PCR),Western blotting and immunohistochemistry.Next, osteosarcoma cells were divided into three groups:HERG-siRNA group,control-siRNA group and blank group. CCK-8,colony formation,flow cytometry and Tunel assay were used to measure the proliferation and apoptosis of the osteosarcoma cells.Finally,Western blotting analysis was performed to detect the expression of nuclear factor-κB (NF-κB)pathway in osteosarcoma cells treated with HERG siRNA.Results Osteosarcoma cells and tissues were found to highly express HERG.Inhibition of HERG in the osteosarcoma cells significantly inhibited the cell proliferation and induced cell apoptosis.Compared to control-siRNA group or blank group,HERG-siRNA could inhibit the proliferation of MG-63 cells significantly [HERG-siRNA group:(75.34 ± 4.45)%;compared to control-siRNA group:(100.60 ±5.31)%;t =3.64,P =0.007;compared to blank group:(100.00 ±5.66)%;t =3.43,P =0.009].The similar results were obtained from colony formation assay (HERG-siRNA group:134.30 ±11.82;compared to control-siRNA group:225.30 ±11.56;t =5.51, P =0.002;compared to blank group:232.80 ±12.21;t =5.80,P =0.001).HERG-siRNA transfected MG-63 cells demonstrated a significant increase of apoptotic rate compared to control-siRNA transfected cells or untreated cells [HERG-siRNA group:(28.10 ±2.21 )%;compared to control-siRNA group:(9.36 ± 2.42)%;t =5.72,P =0.005;compared to blank group:(10.92 ±2.51)%;t =5.14,P =0.007].This resultwas further confirmed by Tunel assay.The cells transfected with HERG-siRNA (31.57 ±2.08)% dem-onstrated extensive apoptosis,compared with the control-siRNA group [(10.35 ±1.82)%;t =7.69,P =0.002)]or blank group [(7.96 ±0.88)%;t =10.48,P =0.001].Silencing HERG gene down-regulated the cIAP-1,XIAP,Bcl-2,Survivin,P-IκBαand NF-κB p65 expression,compared to the control groups. Conclusion HERG is highly expressed in osteosarcoma.HERG silencing can suppress osteosarcoma progres-sion through NF-κB pathway and suggest that HERG may be a novel molecular target for osteosarcoma therapy and diagnosis.

Objective To study the clinical profile of patients with central nervous system (CNS) involvement in relapsing polychondritis (RP).Methods Clinical data of five patients of RP with CNS lesions were collected,and compared with those from the literatures.T test and Fisher exact test were used for statistical analysis.Results Among 205 patients with RP in Peking Union Medical College Hospital,five cases (2.4％) had CNS damage.All 5 cases presented an active onset and occurred in the active phase of RP.All of them manifested as meningoencephalitis,complicating cranial neuropathies in 2 cases (2/5).Cerebrospinalfluid examination revealed non-specific meningeal inflammation,and magnetic resonance image (MRI) showed long T2 signals in brain lesions.Four patients (4/5) showed good response to high-dose glucocorticosteroid plus immunosuppressive agent combined therapy.The average age of our patients was younger than those in the literatures [(44± 14),(58± 11) years,respectively; t=2.547,P＜0.05],while other clinical features was not significantly different between the two groups.Conclusion CNS involvement is a rare condition in RP patients,and usually occurrs in the early course of active RP.Meningoencephalitis/ meningitis is the major clinical manifestations.MRI and cerebrospinal fluid examination may help to confirm the diagnosis.Treatment with corticosteroid and immunosuppressant can result in favorable response.