Background:Fenretinide,which is capable of generating reactive oxygen species( ROS ),has emerged as a promising antineoplastic agent based on numerous in vitro and in vivo studies and clinical chemoprevention trials. Preliminary studies showed that fenretinide could induce apoptosis in human hepatocellular carcinoma( HCC)cells in vitro, however,the precise mechanism was not clarified. Aims:To elucidate the effect of ROS on apoptosis of human HCC cells induced by fenretinide and the underlying mechanism. Methods:Human HCC cell line Huh-7 was treated with antioxidant vitamin E,fenretinide or their combination,respectively. ROS in live cells was evaluated by confocal microscopy and flow cytometry;cell viability and apoptosis were assessed by CellTiter-Glo Luminescent Cell Viability Assay Kit and Caspase-Glo3/7 Assay Kit;expression and intracellular localization of nuclear receptor Nur77,as well as expression of stress-induced transcription factor GADD153 were measured by immunofluorescence staining and Western blotting,respectively. Results:Vitamin E pretreatment fully blocked the fenretinide-induced ROS production. In Huh-7 cells pretreated with vitamin E,cell apoptosis induced by fenretinide was significantly reduced(P<0. 05). Furthermore,effect of vitamin E pretreatment was noteworthy on reducing fenretinide-induced GADD153 expression, while no significant impact on fenretinide-induced Nur77 expression and translocation was observed. Conclusions:Elimination of ROS by vitamin E can abrogate the pro-apoptotic effect of fenretinide on Huh-7 cells,which indicates the participation of ROS in fenretinide-induced apoptosis of human HCC cells. Its mechanism might be associated with induction of GADD153 protein expression.

Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF-7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Artemisinins ; chemical synthesis ; chemistry ; Breast Neoplasms ; pathology ; Cell Proliferation ; Doxorubicin ; Drug Design ; HL-60 Cells ; drug effects ; Humans ; MCF-7 Cells ; drug effects

OBJECTIVETo construct an operable strategic framework for cholera prevention and control which mobilized the advantages of local resources and adapted to social developments in Chengdu, and to evaluate its application effects.

METHODS(1) After analyzing the local epidemic data of cholera in Chengdu from 1994 to 2004, we determined the main problems of cholera prevention and control works as well as the efficiency and deficiency of employed measures, and then formed a basic strategic framework. (2) After 55 invited experts preliminarily scored the strategic framework, we selected 72 specific measures to establish a measure entry database, and then the importance and operability of each measure were scored by 17 core experts. (3) Finally, the effectiveness of this strategic framework was evaluated according to the analyzing results of infection control, health education and etiological monitoring.

RESULTS(1) The framework took government leadership as main scenario and the informatization as subordination scenario. Meanwhile, it focused on three points: the improvement of social environment, the completion of system and mechanisms for monitoring and early warning, and the enhancement of CDC response to public health emergencies. Total importance score and operability score of 35 specific measures included in this framework was 4.20 ± 0.86 and 4.09 ± 0.87, respectively. (2) Chengdu had maintained zero cholera incidence for five consecutive years from 2005 to 2009 since it gradually began to implement the strategic framework in 2002. There were 19 positive cholera cases detected by etiological monitoring and all of them were seafood or fishery products including soft-shelled turtles, silver carps and bullfrogs. The coverage rate and qualification rate of the training for grassroots cadres, grassroots medical workers, mobile cooks and their assistants was 98.14% (198 452/202 220) and 98.17% (194 820/198 452) in average, respectively. The qualification rate of the training for employees in food industry was over 96.00% (912 470/950 489). The average awareness rate of cholera prevention and cure knowledge in rural residents, grassroots cadres, grassroots medical workers, mobile cooks and their assistants was 93.87% (1653/1761) and the average formation rate of good hygiene habits was 70.58% (1243/1761).

CONCLUSIONA strategic framework suitable for cholera prevention and control in Chengdu has been successfully established in this study. The incidence rate of cholera has maintained zero in Chengdu for five consecutive years under incessant threatening conditions such as the occurrence of cholera cases from time to time in its surrounding areas and the continuous existence of Bacillus comma in seafood or fishery products that entered local markets. Therefore, it demonstrated a good application effects.

China ; epidemiology ; Cholera ; epidemiology ; prevention & control ; Communicable Disease Control ; organization & administration ; Health Education ; organization & administration ; Humans ; Outcome Assessment (Health Care) ; Public Health

OBJECTIVETo investigate the possibility to enhance the proliferation of adipose-derived stem cells (ASCs) in a delayed fat flap in rabbits.

METHODSA delayed fat flap was formed in one side of inguinal region of a rabbit. 21 days after operation, the fat tissues at the delayed flaps and at the unoperated side were harvested and digested with 0.25% collagenase and sieved. The cell suspensions were centrifuged. The cells were obtained from tissue precipitate after centrifugation. The expression rates of the surface marker (CD29, CD44, CD14 and CD45) were measured by FCM and compared between the experimental and control groups.

RESULTSExpression rates of CD29 and CD44 were higher in the delayed fat flap (74.06% and 90.74%) than in the contralateral fat tissue (62.88% and 77.54%, P < 0.05), while those of CD14 and CD45 were lower in the delayed fat flap (57.66% and 4.84%) than in the contralateral fat tissue (72.10% and 75.82%, P < 0.05 and P < 0.01).

CONCLUSIONSTissue hypoxic ischemia such as fat tissue in a delayed fat flap can promote proliferation of ASCs. It indicates that tissue in the delayed flap may be transplanted with better survival rate. The ischemia pretreatment of fat tissue may become a new method for fat transplantation.

Adipose Tissue ; cytology ; transplantation ; Animals ; Cell Proliferation ; Cells, Cultured ; Graft Survival ; Postoperative Period ; Rabbits ; Stem Cells ; cytology ; Surgical Flaps

OBJECTIVETo investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells.

METHODSFifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot.

RESULTSCompared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01).

CONCLUSIONSExtract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.

Animals ; Cathepsin B ; metabolism ; Cystatin C ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hydrogen Peroxide ; Lutein ; pharmacology ; Macular Degeneration ; prevention & control ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred C57BL ; Pigment Epithelium of Eye ; drug effects ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Xanthophylls ; pharmacology ; Zeaxanthins

Objective To investigate the clinical value and surgical methods of pancreaticoduodenectomy (PD) combined with portal vein (PV)/superior mesenteric vein (SMV) resection and reconstruction in the treatment of pancreatic cancer with PV/SMV invaded by tumor.Methods The clinical data of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) and 62 patients of pancreatic head cancer without PV/SMV invaded by tumor (group B) in the same period were collected and analyzed retrospectively from Jan 2014 to Apr 2017.There were no distinct invasion of celiac artery (CA),hepatic common artery (HCA) and superior mesenteric artery (SMA) in two groups of pancreatic cancer patients.The patients of group A underwent PD combined with PV/SMV resection and reconstruction,and the patients of group B were only treated with PD surgery.The complication rate and overall survival time after PD was compared between the 21 patients of pancreatic cancer with PV/SMV invaded by tumor and the 62 patients of pancreatichead cancer without PV/SMV invaded by tumor.'Results The average overall survival time of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) was 19.2 months,specifically with 1-year survival rate of 57.1％ (12/21),2-year survival rate of 28.6％ (6/21),and 3-year survival rate of 14.3％ (3/21).Meanwhile,the average overall survival time of group B was 19.4 months,specifically with 1-year survival rate of 58.1％ (36/62),2-year survival rate of 30.6％ (19/62),and 3-year survival rate of 14.5％ (9/62).The results indicated that no differences for overall survival time of patients treated with PD including 1,2,3-year survival rate between two groups were found (P ＞ 0.05).Conclusions For pancreatic cancer accompanied by PV/SMV invasion without invasion of SMA,CA and HCA,PD combined with PV/SMV resection and reconstruction are safe and feasible surgical procedures.The surgical reconstruction method was determined according to the location and length of the invaded vessels,and also there were no significant differences on the complication rate and overall survival time after PD between the pancreatic cancer patients with invasion of PV/SMV and the pancreatic head cancer patients without invasion of PV/SMV.

Objective To investigate the efficacy of transvenous embolization in the management of cavernous dural arteriovenous fistulas. Methods Nine patients with cavernous dural arteriovenous fistulas diagnosed by digital subtraction angiography (DSA) were treated by transvenous embolization. Results Eight of the 9 patients were cured and 1 patient showed symptomatic improvement after the operations. No deterioration or death occurred in these cases. Follow-up of the patients for 2 to 96 months found no cases of relapse or exacerbation. Conclusion Transvenous embolization is effective and safe in the management of cerebral dural arteriovenous fistulas.

OBJECTIVEDetecting hepatitis B virus large surface protein (HBLP) with serological method to filtrate the occult HBV infection and study the clinical detection strategy.

METHODSTwo thousands HBsAg negative stochastic serum samples were collected from the copy tubes in daily work to detect hepatitis B Virus markers (HBVM) with national EHSA regent kits and put them -20 degrees C frostily. The 2000 samples were detected with HBLP and filtrated the positive samples. The HBsAg markers were doubly counterchecked with other two adding kinds of national ELISA regent kits (total 3 kinds) at the filtrated samples. The last samples were doubly tested again with American MONOLISA HBsAg ULTRA regents. HBV DNA levels were quantitative analyzed with fluorescence quantitative PCR (FQ-PCR) and taking the mean results.

RESULTSFifteen HBLP positive samples were detected out from the 2000 serum samples. We educed the conform negative results from the three kinds of national regents but conform positive results from the American MONOLISA HBsAg ULTRA regents in repeating HBsAg detection at the 15 samples. The HBV DNA FQ-PCR quantitative results were all less than 500 copies/mi and divided into two cases hetween 400-500 copies/nil, three cases 300-400 copies/ml, five cases 200-300 copies/ml, four cases 100-200 copies/ml and one case was less than l00copies/ml.

CONCLUSIONThe false HBsAg negative results for serum samples are more generally through national regents than through importations and HBLP results mayhe are positive in these samples. Detecting HBLP marker is propitious to filtrate the occult HBV infection. This study provided a kind of serological reference for actively searching for the detecting strategy in occult HBV infection field.

Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Hepatitis B ; blood ; diagnosis ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; Humans ; Male ; Viral Envelope Proteins ; blood

Objective To analyze the therapeutic effects of microvaseular decompression on primary trigeminal neuralgia. Methods The general clinical data,culprit vessels and therapeutic effects of the surgical interventions were analyzed in 181 patients(aged from 24 to 79 years with a mean of54.9 years,including 78 male and 103 female patients)with established diagnosis of primary trigeminal neuralgia admitted from January,2000 to Deceber,2007. Results Blood type O was present in 43.65%of the 181 patients with trigeminal neuralgia,which had an increasing tendency compared to the national norm(33.8%).The morbidity ratio between the right and left side was 1.8:l in these patients.Forty-five patients(24.86%)were identified to have more than 2 culprit vessels.The culprit vessels included the superior cerebellar artery(96 cases),posterior inferior cerebellar artery(7 cases),anterior inferior cerebellar artery(25 cases),arteries communicated with veins(25 cases),internal auditory artery (13 cases),basilar artery(15 cases),vertical artery(9 cases),exclusive veins(15 cases,mainly vena pelrosa and bridging vein)and unknown vessels(9 cases).of the 181 cases,171(94.48%)were cured within one month,9(4.97%)showed relieved symptoms but required drug therapy,and 1 was in vegetative state(0.55%). Conclusions Patients with blood type O may have greater chance of developing primary trigeminal neuralgia.Microvascular decompression is an ideal treatment for primary trigeminal neuralgia,and clear identification of the culprit vessels can be crucial for decreasing the postoperative recurrence.

This study was designed to compare the curative effect, prognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphoma (ML). The clinical data of 100 ML patients (Sep 1992 to Aug 2010 in 307 Hospital) were retrospectively analyzed, and were divided into two groups by different preconditioning regimens: the high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group. The overall survival (OS) rate, progress free survival (PFS) rate and adverse effect were analyzed. The results showed that until Feb 2011, the median follow-up was 33.5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1.0×1.0(9)/L in high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group were (6.0 ± 0.4) d and (8.2 ± 0.4) d, platelet up to > 20.0×1.0(9)/L in two groups were (7.1 ± 0.8) d and (11.4 ± 2.5) d (P < 0.05). The 3-year OS rate of the two groups were 67.3% and 68.9%. 5-year OS rates of two groups were 62.8% and 60.6%, 10-year OS rates of two groups were 57.6% and 56.2% respectively; 3-year PFS of two group were 63.6% and 63.2%, 5-year of two group were 59.4% and 58.3%, 10-year of two group were 50.8% and 55.3% respectively (P > 0.05). Meanwhile, the incidence of fever, infection, bleeding, secondary cancer between two groups was not significant different (P > 0.05). It is concluded that the hematopoietic reconstitution of high-dose chemotherapy/radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However, there is no significant difference in curative effect and prognosis between the two groups.
Adolescent ; Adult ; Aged ; Child ; Combined Modality Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma ; surgery ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Transplantation Conditioning ; methods ; Transplantation, Autologous ; Young Adult