Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Objective To detect the sera anti-enteric neuronal antibodies ( AENA ) in irritable bowel syndrome with diarrhea ( IBS-D) patients and analyzed its correlation with IBS-D symptoms to explore the potential roles of AENA in the pathogenesis of IBS.Methods IBS-D patients diagnosed with RomeⅢdiagnostic criteria were en-rolled in this study.The sera of healthy subjects were used as controls.Indirect immunofluorescence ( IIF) was used to detect the sera AENA with the substrate of ileal submucosal plexus of guinea pig .The immune reactivity ( IR) stains were read in blinded method .The bowel symptoms of patients with positive AENA were compared to thatwithnegativeandweeklypositiveantibodies.Results 1)Atotalof127IBS-Dpatientswereenrolledinthis study.The positive rate of sera AENA was 85.8%in IBS-D patients, and 7.0%in healthy controls.Among 109 IBS-D patients with positive IIF reactivity , 23.6%present with strong positive , 43.3% with positive and 18.9%with weakly positive stain .The IR patterns included cytoplasm staining , nucleus staining , cytoplasms and nuclei staining , nuclear membrane staining , cytoplasm and nuclear membrane staining .Six positive sera of healthy control showed cytoplasm staining to substrate neurons .2 ) More patients of IBS-D with positive IR had higher intestinal symptoms scores (>10 scores, 58.8%vs 38.1%), frequent abdominal pain in non-defecation period (91.7%vs 60.0%) , and severe abdominal pain/discomfort before defecation ( 24.7% vs 9.5%) comparing to those with negative and weekly positive IR of AENA;IBS-D patients with positive IR of AENA are more commonly associated with urgency comparing to those with negative IR in IIF (57.1%vs 87.3 ) .Conclusions AENA may play a role in the pathogenesis of IBS , and is a potential biomarker of IBS-D.

Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems. Among all the organs, liver is one of the most remarkable targets of T. wilfordii-induced toxicities, and the damage is more serious than others. It is generally accepted that T. wilfordii-induced liver injury is a result of the combined effects of toxic elements of T. wilfordii. It is reported in several studies that the mechanism of T. wilfordii-induced liver injury may be related to lipid peroxidation, cell apoptosis and immune damage, and so on. Licorice is one of the most commonly used Chinese herbal medicine, with effects of heat- clearing and detoxicating, anti-inflammatory and hepatoprotective, reconciling various drugs, and so on. Licorice often accompany T. wilfordii in clinical application which can significantly reduce the liver injury induced by T. wilfordii. The attenuated effect is exact, but the mechanism is still a lack of in-depth study. This paper reviews the studies on T. wilfordii-induced liver injury and the related mechanism as well as licorice and other traditional Chinese medicine accompany T. wilfordii to reduce the injury in recent years, so as to provide reference for related research in the future.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Glycyrrhiza ; Humans ; Inactivation, Metabolic ; Medicine, Chinese Traditional ; Tripterygium

OBJECTIVETo explore methods and clinical outcomes of microsurgical technique in treating patients with severed palm.

METHODSFrom January 2009 to December 2012,45 patients with severed palm were treated by replantation through microsurgical technique, included 37 males and 8 females, aged from 13 to 45 years old with an average of 25. Postoperative survival rate and evaluation standard of upper limb replantation function posposed by Chinese Medical Association were applied for evaluate clinical outcomes after operation.

RESULTSForty-five patients with severed plam were treated by replantation. Thirty-nine patients (121 fingers) were survived,and survival rate was 87%. All patients were followed up 3 to 15.5 months with an average of 11.5 months. According to evaluation standard of upper limb replantation function posposed by Chinese Medical Association, the total score was 80.27 +/- 1.93, and 27 cases got excellent results, 8 good and 4 poor.

CONCLUSIONThe success of replantation of severed palm depends on grasping operation indication strictly, knowing complexity and local anatomic relationship, debridement completely during operation, making full use of remaining organization, arteriovenostomy through microsurgical technique as early as possible, constructing circulation and repairing injuried nerve rationally.

Adolescent ; Adult ; Female ; Hand Injuries ; physiopathology ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Replantation ; Young Adult

Objective To evaluate prourodynamic study and somatosensory evoked potentials(SEPs)before and after operation of children with lipomyelomeningocele(LMMC)and its clinical significance.Methods Urodynamic study(UDS)and SEPs in 31 cases of LMMC who underwent microsurgical release within 1 week preoperatively and 3 months postoperatively were conducted.The 4 parameters used for UDS evaluation were bladder volume,compliance,detrusor activity and residual urine;parameters used for SEPs evaluation were latent period and amplitude.Results There was a statistics significant difference between operation and control group;the similar result was attented in the comparison of before and after operation,also in the comprison of the improved group and the group without improvement after operation.Conclusions UDS and SEPs investigation can provide guidance for the treatment of tethered cord syndrome(TCS)and evaluate clinical prognosis.These cases with the severity changing in UDS and somatosensory shall be avoided unnecessary action in operation.

OBJECTIVETo summarize our experiences with the treatment of non-small cell lung cancer (NSCLC) with cetuximab and compare the therapeutic effects of cetuximab applied in the first line and non-first line settings.

METHODSFrom October 1, 2006 to December 31, 2009, 16 NSCLC patients were treated with cetuximab combined with standard chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy of the therapeutic protocols were analyzed.

RESULTSA total of 115 cycles of cetuximab treatment were administered in these patients with a median of 6 cycles (7.5 in the first line setting and 2 in non-first line setting). In the 10 patients with cetuximab treatment in the first line setting, the ORR was 40.0% (4/10), DCR was 80.0% (8/10), median TTP was 6.5 months (2-19), and median OS was 8.5 months (2-48); in the non-first line setting, these indices were 33.3% (2/6), 33.3% (2/6), 3.5 months (3-4) and 18 months (4-28), respectively. Both ORR and DCR were similar between the first and non-first line settings (P=0.790, P=0.062). Ten of the patients (62.5%) developed acne-like rash within 3 weeks, who had an ORR of 60% (6/10) and DCR of 90% (9/10); the ORR and DCR in patients without acne-like rash were both 10.4% (1/6), showing no significant difference in ORR (P=0.080) but a significant difference in DCR between the two groups (P=0.003). No treatment-associated death or cetuximab-associated discontinuation occurred. Altogether 11 patients (68.8%) developed acne-like rash, which occurred within 3 weeks in 10 cases. Seven patients showed side effects associated with the chemotherapy.

CONCLUSIONCetuximab combined with standard chemotherapy is a good option for Chinese patients with NSCLC and the current data support the application of cetuximab in the first line setting.

Adult ; Aged ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cetuximab ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo study the autophagy activity between rat bone marrow stem cells (BMSCs) neural differentiation in order to explore the mechanism involve in this process.

METHODSBMSCs were passed by 3 generation, then was induced with the revulsant 2% (DMSO) + 200 µmol/L (BHA), NSE expression was detected by immunocytochemical stain, the mRNA expression of autophagy associated genes L3B, Beclinl, Atg5, Atg7, Atg10 were detected by RT-PCR, the autophagy protein LC3B was examined by Western blot and flow cytometry analysis.

RESULTSBMSCs were passed by 3 generation, the purity of BMSCs could reach more than 90%, the morphology of cells were like fibroblasts, after the revulsant 2% DMSO + 200 µmol/L BRA induced, cells were extended long neurites, like nerve cells, positive rate of NSE staining was (83±5) %, RT-PCR results showed that the expression of autophagy associated genes LC3B, Beclinl, Atg5, Atg7 Atg0 were rised after BMSCs neural differentiation, Western blot analysis showed that the LC3B-II protein expression was increased after neural differentiation and the MFI of L3B was highten by flow cytometry.

CONCLUSIONAutophagy is increased after rat BMSC neural differentiation.

Animals ; Autophagy ; Cell Differentiation ; Cells, Cultured ; Flow Cytometry ; Mesenchymal Stromal Cells ; cytology ; Neurons ; cytology ; Rats

Objective To determine the prevalence and risk factors of hyperuricemia (HUA) and gout among residents aged≥20 years in Shandong coastal areas compared with the results of 2004. Methods A randomized stratified cluster sampling was conducted, and 5 191 inhabitants were investigated for prevalences of HUA and gout in Qingdao, Yantai, Weihai, Rizhao, and Dongying. Results (1)The level of serum uric acid had the tendency to increase in both males and females in 2009 compared with that in 2004. (2)According to the uniform population standardization, the standardized prevalence of HUA was 16.99%in 2009. The standardized rate increased by 3.72%compared to 2004, being 4.57%in males and 3.33%in females. (3) The standardized prevalence of gout was 1.36%. Compared with that in 2004, the standardized rate increased by 0.26%, decreased by 0.45%in males while increased by 0.85%in females. (4) Compared to 2004, the prevalence of HUA among males aged≤30 years was the highest, whereas aged between 50 years and 60 years was the lowest at present. (5) Currently, the prevalence of HUA among females aged≤30 years was significantly higher than that of 2004, and aged≥70 years was the highest. (6) Logistic regression analysis showed that the amount of daily intake of seafood, meat, beer, and liquor were independent risk factors of HUA and gout. Conclusions Compared to 2004, the level of serum uric acid and the prevalence of HUA and gout show a tendency to increase among younger in the population surveyed in 2009, significant in female. Dietary factors exert significant effects on the development of HUA and gout. The amount of daily intake of seafood, meat, beer, and liquor are independent risk factors of HUA and gout.

Objective To construct a new conditionally replicative adenovirus (CRAds) targeting carcinoembryonic antigen (CEA) positive colorectal cancer cells. Methods The DNA fragment of the CEA gene promoter was amplified through PCR and cloned into the vector carrying fusion reporter gene EGFP-Luc to construct expression plasmid pCEA-EGFPLuc. The constructed plasmid pCEA-EGFPLuc was transfected into CEA positive and negative cells by liposome. The activity of CEA gene promoter was evaluated by detecting the expression of EGFP and luciferase activity. The conditionally replicative adenovirus Ad.CEA-E1A/CMV-TK carrying suicide gene HSVtk was constructed, in which the E1A gene was controlled under CEA promoter. CEA positive(Lovo and SW620)and negative tumor cells(HeLa) were infected with Ad.CEA-E1A/ CMV-TK. The selective cytotoxicity of Ad.CEA-E1A/CMV-TK and the synergistic effect of the virus with GCV in CEA positive tumor cells were evaluated by the expression of E1A, cytopathic effect and cell survival rate. Results CEA promoter possesses a good specificity as well as high activity. The expression of E1A only presented in CEA positive tumor cells. After infection with Ad. CEA-E1A/CMV-TK, the cell survival rates of Lovo and SW620 were (36.72±2.49)% and (39.82±4.76)%, respectively, significantly lower than that of Hela[(87.44±2.76)%1 (P<0.01). When combined with GCV, Ad.CEA-E1A/CMV-TK had better oncolytic effect on Lovo and SW620 cells, with cell survival rates of (17.26±3.65) % and (23.93±5.40) %, respectively, significantly lower than those without GCV[(36.72±2.49) % and (39.82±4.76) %, respectively] (P<0.01). Conclusion Ad. CEA-E1A/CMV-TK under the control of CEA promoter has selective cytotoxic effect on CEA positive colorectal cancer cells, and the effect can be enhanced when combined with GCV.

OBJECTIVERegional left ventricular (LV) function could be detected by measuring peak-systolic strain by speckle tracking imaging (STI). We evaluated the value of STI combined with adenosine stress echocardiography on assessing myocardial viability in patients with myocardial infarction (MI).

METHODSTwo dimensional echocardiography was performed at rest and after adenosine stress echocardiography (infused at 140 µg×kg(-1)×min(-1) over a period of 6 min) in 39 stable patients with previous MI. Peak-systolic (Speak-sys) circumferential strain, radial strain and longitudinal strain were assessed by STI. Radionuclide myocardial perfusion/metabolic imaging served as the "gold standard" to detection of myocardial viability.

RESULTS(1) There were 215 viable and 153 non-viable regions among 368 abnormal motion segments out of 624 segments in 39 MI patients according to radionuclide imaging results. (2) Speak-sys was similar between viable and nonviable myocardium at rest (all P > 0.05). After adenosine infusion, radial Speak-sys [(37.98 ± 5.45)% vs. (30.22 ± 5.47)%], longitudinal Speak-sys [(-23.71 ± 4.53)% vs. (-17.52 ± 4.34)%] increased significantly (P < 0.05)in viable segments compared to baseline levels and were significantly higher than in nonviable segments radial Speak-sys [(37.98 ± 5.45)% vs. (30.12 ± 5.37)%] and longitudinal Speak-sys [(-23.71 ± 4.53)% vs. (-16.95 ± 4.62)%] (P < 0.05), while remained unchanged in nonviable segments before and after adenosine infusion. Circumferential Speak-sys was similar before and after adenosine infusion in both viable and nonviable segments (all P > 0.05). (3) Delta radial strain change > 9.8% has a sensitivity of 82.3% and a specificity of 81.1% whereas a delta change of longitudinal strain > 16.5% has a sensitivity of 83.5% and a specificity of 92.3% for detecting viable segments.

CONCLUSIONSSpeckle tracking imaging combined with adenosine stress echocardiography could serve as a new and reliable method of assessing myocardial viability.

Aged ; Aged, 80 and over ; Cell Survival ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; Myocardium ; cytology ; Radionuclide Imaging