1.Inhibition of a small interfering dsRNA targeting hypoxia inducible factor-1α on retinal neovascularization in mice
Wei-tao, SONG ; Xiao-bo, XIA ; Si-qi, XIONG
Chinese Journal of Experimental Ophthalmology 2012;30(4):311-315
BackgroundHypoxia-inducible factor-1 α (HIF-1α) specific double-stranded RNA ( dsRNA ) mediated by liposome inhibit reinal neovascularization in mice at dose-dependent manner. ObjectiveThe present study was to investigate the inhibitory effect of dsRNA targeting HIF-1α on retinal neovascularization in mice.MethodsModels of oxygen-induced retinal neovascularization were set up in C57BL/6J mouse through exposure of postnatal day 7 ( P7 ) to (75±3) % oxygen for 5 days.Fluorescein conjugated Dextran angiography of retinal vascular was performed to identify the retinal neovascularization.The 8 mice of the normal group were raised in the room air.Fifty-one P7 mice exposed to(75±3)% oxygen for 5 days and then returned to the room air and assigned to control group ( 3 mice),empty vector group( 3 mice) and gene therapy group (45 mice),and the latter were medially divided to 9 groups randomly according to dose-ratio ( liposomes ∶ plasmid).The pSilencer 2.1-U6 hygro was injected in the model mice of empty vector group,and different dose-ratios of pSilencer2.1-U6 hygro-HIF-1α dsRNA were injected respectively in the model mice of various gene therapy groups.Fluorescein conjugated Dextran angiography of retinal vascular was performed to observe the morphology of new blood vessels,and retinal slides were prepared to score the numbers of nuclei extending beyond the inner limiting membrane( ILM ),and expression of vascular endothelial growth factor(VEGF) was detected in the retina by immunohistochemistry.Results The retinal blood vessels of the normal group formed a fined radial branching pattern.The retinal vascular patterns in the control group and the empty vector group were characterized by decreased central perfusion in both the superficial and the deep layers.The abundant vessels were distorted and irregular in the control group and empty vector group,and the obstructed capillary and lots of neovascular tufts were seen.The retinal neovascularization and non-perfusion distraction in the every gene therapy group were reduced markedly with the most severe appearance in 1 ∶ 1 ( liposomes ∶ plasmid) dose-ratio group.Few vascular endothelial cell nucleus extending beyond the ILM were found in the normal group;while a large number of vascular endothelial cell nucleus were showed in the control group and empty vector group with the occurring rate 100%.Statistically,no significant difference was seen in the number of nuclei extending beyond the ILM between the control group and the empty vector group(11.57±5.85 vs 11.53±6.15),however,that in 1∶1 (liposomes∶plasmid) group was reduced markedly ( 2.17 ± 4.23 ) ( P < 0.01 ).Immunohistochemistry revealed that VEGF was faintly expressed in the normal group but strongly expressed in the control group and the gene therapy group.VEGF expressions of various gene therapy groups were weaker than ones of the control group and the empty vector group.ConclusionsRetinal neovascularization can be efficiently inhibited by intravitreal injection of the pSilencer2.1-U6 hygro-HIF-1α dsRNA mediated by liposome.Proportion of 1 ∶ 1 (liposomes ∶ plasmid)has a maximized efficiency.
2.Expression of transcriptional factor lslet-1 in retina with experimental retinal neovascularization induced by oxygen
Si-Qi, XIONG ; Hai-Bo, JIANG ; Hui-Zhuo, XU ; Xiao-Bo, XIA
International Eye Science 2014;(12):2127-2130
AlM:To evaluate the expression of transcriptional factor lslet-1 in retina in experimental retinal neovascularization induced by oxygen.
METHODS: The murine retinal neovascularization were induced by hyperoxia exposure. The morphological observation of retinal neovascularization was performed using angiography by fluorescein dextran injection under the fluorescence microscope, and the new blood vessels were quantified after 5d in room air (17-day-old) by counting the vascular epithelial cell nuclei protruding into viteous cavity using HE stain. Realtime PCR and Western blot were used to examine retinal lslet-1 level in postnatal 7,12, 14,17 and 26d respectively.
RESULTS: A lots of new blood vessels were demonstrated in the mouse retina in hyperoxic group by fluorescein angiography and histological method. Moreover, no significant difference was found in retinal lslet-1 level in postnatal 7d between hyperoxic group and control group, but was significantly higher in postnatal 12, 14 and 17d mice compared with control mice. However, mice at postnatal 26d, expression of lslet-1 in retina decreased to normal level.
CONCLUSlON: ln processing mouse model of retinal neovascularization, sustained hypoxia retinal tissue induce retinal neovascularization by increas the expression of transcription factor lslet-1.
3.HIF-1α siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity.
Hui-Zhuo XU ; Shuang-Zhen LIU ; Si-Qi XIONG ; Xiao-Bo XIA
Chinese Journal of Contemporary Pediatrics 2011;13(8):680-683
OBJECTIVETo study the inhibition effect of HIF-1α specific siRNA expression vector pSUPERH1-siHIF-1α on retinal neovascularization in a mouse model of retinopathy of prematurity (ROP).
METHODSThe mouse model of ROP was prepared by the method Smith described. Forty-eight ROP mice were randomly divided into two groups: an experimental group that was intravitreously injected with pSUPERH1-siHIF-1α and a control group that was injected with pSUPER retro vector. The levels of HIF-1α and vascular endothelia growth factor (VEGF) in the retina were examined by Western blot. The retinal neovascularization was evaluated by angiography using FITC Dextran and quantitated histologically.
RESULTSThe levels of HIF-1α and VEGF in the retina in the experimental group were reduced 90% and 65% respectively compared with those in the control group. Meanwhile, the number of retinal neovascular endothelial nucleus outbreaking the inner limit membrane in the experimental group was significantly reduced compared with that in the control group.
CONCLUSIONSThe development of retinal neovascularization of ROP can be markedly inhibited by RNA interference targeting HIF-1α.
Animals ; Disease Models, Animal ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; analysis ; antagonists & inhibitors ; genetics ; Infant, Newborn ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; genetics ; Retinal Neovascularization ; prevention & control ; Retinopathy of Prematurity ; therapy ; Vascular Endothelial Growth Factor A ; analysis
4.Assessment of quality of life for the patients with cervical cancer at different clinical stages.
Yao XIE ; Fang-Hui ZHAO ; Si-Han LU ; He HUANG ; Xiong-Fei PAN ; Chun-Xia YANG ; You-Lin QIAO
Chinese Journal of Cancer 2013;32(5):275-282
With improved overall survival of cervical cancer patients, the importance of the quality of life (QOL) is increasingly recognized. This study was conducted to compare the QOL of women with different stage cervical cancer before and after treatment to facilitate improved cervical cancer prevention and treatment. We used the generic Medical Outcomes Study Short Form-36 (MOS SF-36) to collect QOL information. Based on SF-36, we interviewed cervical cancer patients at West China Second Affiliated Hospital and Sichuan Cancer Hospital between May 2010 and January 2011. A total of 92 patients with precancerous lesions, 93 with early cancer, and 35 with advanced cancer responded to our survey. Average physical component summary (PCS) scores were significantly different between the three groups at every time point (P < 0.05). Average mental component summary (MCS) scores were significantly different between the three groups after treatment (P < 0.05). Average PCS and MCS scores increased gradually from the pretreatment to posttreatment period for patients with precancerous lesions. However, they reached the lowest at 1 month after treatment for patients with early and advanced cancers and rebounded between 1 and 6 months after treatment. Our results indicate that patients with precancerous lesions and early cervical cancer show better overall QOL than do those with advanced cervical cancer. Additionally, patients with early cancer recover more quickly than do those with advanced cancer in terms of both physical and mental functions. Thus, early detection and treatment initiatives may improve the QOL for patients with precancerous lesions and cervical cancer.
Adult
;
Aged
;
Carcinoma in Situ
;
pathology
;
therapy
;
Cervical Intraepithelial Neoplasia
;
pathology
;
therapy
;
Chemoradiotherapy
;
China
;
Female
;
Follow-Up Studies
;
Humans
;
Hysterectomy
;
methods
;
Lymph Node Excision
;
Middle Aged
;
Neoplasm Staging
;
Precancerous Conditions
;
pathology
;
therapy
;
Quality of Life
;
Surveys and Questionnaires
;
Uterine Cervical Neoplasms
;
pathology
;
therapy
;
Young Adult
5.Incidence and mortality of liver cancer in China, 2010.
Kuang-Rong WEI ; Xia YU ; Rong-Shou ZHENG ; Xia-Biao PENG ; Si-Wei ZHANG ; Ming-Fang JI ; Zhi-Heng LIANG ; Zhi-Xiong OU ; Wan-Qing CHEN
Chinese Journal of Cancer 2014;33(8):388-394
Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population (ASR China), and age-standardized rate by world standard population (ASR world) were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85+. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.
China
;
epidemiology
;
Female
;
Humans
;
Incidence
;
Liver Neoplasms
;
epidemiology
;
mortality
;
Male
;
Registries
;
Rural Population
;
Sex Distribution
;
Urban Population
6.Gonadotrophin dose and ovarian response: relations to the clinical outcome of in vitro fertilization and embryo transfer.
Xia-si XIONG ; Shi-ling CHEN ; Ling SUN ; Min-na YIN ; Er-yong ZHAO ; Juan SONG
Journal of Southern Medical University 2008;28(5):712-714
OBJECTIVETo investigate the association of gonadotrophin (Gn) dose and ovarian response with the clinical outcome of in vitro fertilization and embryo transfer (IVF-ET).
METHODSPatients undergoing IVF-ET with Gn stimulation for no more than 15 days were enrolled in this study. The patients were divided into 3 groups, namely group A (390 cycles) with total Gn dose :3375 IU and retrieved oocytes:4, group B (64 cycles) with total Gn dose :3375 IU and retrieved oocytes < or =3, and group C (97 cycles) with total Gn dose< or =3300 IU and retrieved oocytes< or =3. The clinical characteristics and outcomes of these 3 groups were comparatively analyzed.
RESULTSThe clinical pregnancy rate and delivery rate were 38.8% and 32.5% in group A, 16.7% and 10.4% in group B, and 27.3% and 23.4% in group C, respectively. The follicle number, oocyte number, number of embryo transferred, peak serum E2 level, clinical pregnancy rate and delivery rate were significantly higher in group A than in groups B and C (P<0.05). Groups B and C had similar follicle number, oocyte number, and number of available embryos, but group C had significantly lower total Gn dose (P<0.05); the peak serum E2 level, clinical pregnancy rate and delivery rate were lower in group B than in group C, but the difference was not statistically significant (P>0.05).
CONCLUSIONSIn patients receiving a relatively low dose of Gn with smaller number of retrieved oocytes, Gn dose increment can improve the clinical pregnancy rate and delivery rate, suggesting a state of relatively poor ovarian response or mild ovarian reserve decrease; failure of increasing the number of oocytes retrieved with greater Gn dose suggests severely decreased ovarian responsiveness or ovarian reserve and also poor clinical prognosis.
Adult ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropins ; administration & dosage ; pharmacology ; Humans ; Infertility, Female ; physiopathology ; therapy ; Ovarian Follicle ; drug effects ; physiopathology ; Ovary ; drug effects ; physiopathology ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Outcome
7.Influence of chronic HBV infection in the husband on the outcome of IVF-ET treatment.
Er-yong ZHAO ; Shi-ling CHEN ; Ling SUN ; Min-na YIN ; Xia-si XIONG ; Juan SONG ; Ya-nan SONG ; Yuan-ping ZHOU
Journal of Southern Medical University 2007;27(12):1827-1829
OBJECTIVETo investigate the outcome of in vitro fertilization and embryo transfer (IVF-ET) in couples with the husband positive for chronic infection of hepatitis B virus (HBV).
METHODSThis study involved 102 infertile couples receiving IVF-ET with the husbands(but not the wives) positive for hepatitis B surface antigen (HBsAg), and another 204 couples negative for HBsAg receiving the treatment served as the control group. The cumulative embryo score, fertilization rate, cleavage rate, rate of good quality embryos, implantation rate, clinical pregnancy rate, first trimester and late miscarriage rates, delivery rate, and neonatal malformation rate were recorded and compared between the two groups.
RESULTSBetween the HBsAg-positive and the control groups, the cumulative embryo score (52.8-/+18.7 vs 55.4-/+16.9), insemination rate (66.9% vs 66.1%), cleavage rate (97.6% vs 97.2%), rate of good quality embryos (34.0% vs 37.1%), implantation rate (40.9% vs 34.6%), clinical pregnancy rate (56.9% vs 50%), first trimester miscarriage rate (6.9% vs 5.9%) and late pregnancy miscarriage rate (8.6% vs 4.9%), delivery rate (40.2% vs 43.6%) and neonatal malformation rate (0 vs 0) were all similar (P>0.05;).
CONCLUSIONChronic HBV infection in the husband might not affect the outcome of IVF-ET treatment.
Case-Control Studies ; Embryo Transfer ; Female ; Fertilization in Vitro ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; physiopathology ; Humans ; Male ; Pregnancy ; Pregnancy Outcome
8.Favorable prognosis of female patients with nasopharyngeal carcinoma.
Xing LU ; Fei-Li WANG ; Xiang GUO ; Lin WANG ; Hai-Bo ZHANG ; Wei-Xiong XIA ; Si-Wei LI ; Ning-Wei LI ; Chao-Nan QIAN ; Yan-Qun XIANG
Chinese Journal of Cancer 2013;32(5):283-288
The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.
Adolescent
;
Adult
;
Age Factors
;
Aged
;
Aged, 80 and over
;
Chemotherapy, Adjuvant
;
Child
;
Female
;
Follow-Up Studies
;
Humans
;
Male
;
Middle Aged
;
Nasopharyngeal Neoplasms
;
diagnosis
;
drug therapy
;
pathology
;
radiotherapy
;
Neoplasm Staging
;
Prognosis
;
Radiotherapy, High-Energy
;
Sex Factors
;
Survival Rate
;
Young Adult
9.Influence of Niaoshi No.2 Formula on Urinary NAG,γ-GT,Serum β2-MG,NAG and CysC in Patients with Kidney Stone After ESWL Surgery
Bao-Guo CHEN ; Li-Ying QIU ; Liu YANG ; Ian Yu-j HU ; Ling-Zhu XIONG ; Si-Xia YANG
Journal of Nanjing University of Traditional Chinese Medicine 2017;33(1):19-22
OBJECTIVE To explore the biological effects of extracorporeal shock-wave lithotripsy(ESWL) on kidney dam-age as well as the preventive and therapeutic effects of Niaoshi No.2 Formula.METHODS 60 cases with kidney stone who re-ceived ESWL surgery were randomly divided into two groups.Patients in the control group were given the routine treatment including giving large volume of water,resisting infection,removing urinary stone based on body position and dealing with the symptoms,while those in the treatment group were given Niaoshi No.2 Formula from three days before ESWL surgery to the seventh day after the surgery.Changes of urinary NAG,gamma-GT,serum beta2-MG,NAG and CysC were detected before ESWL and 24 h,72 h,and 1 68 h after operation in the two groups.RESULTES The contents of urinary NAG,γ-GT,serumβ2-MG,NAG and CysC obviously increased 24 h after surgery when compared with the situations before(P <0.01);Urinary NAG and serum NAG in the treatment group were evidently lower than those of the control group 24 h and 72 h after ESWL surgery(P < 0.05 ~ 0.01).Ureases of both groups were able to return to normal situation within 1 68 hours after surgery. CONCLUSION ESWL surgery can cause damage to kidney,which is reversible within a certain time and scope.Chinese medi-cine Niaoshi No.2 Formula has swift and good effects on kidney damage in patients after receiving ESWL surgery.
10.Selenium compound induces apoptosis of cervical carcinoma cells of high risk HPV subtypes
qi Jie XIONG ; 江西省妇幼保健院 ; Ling GUO ; Xia CHEN ; lei Yuan LOU ; sun Si LIU ; Fei GUO
Basic & Clinical Medicine 2017;37(12):1712-1719
Objective To investigate the inducing effects and related pathways of selenium dioxide ( SeO2 ) on the apoptosis in 2 human cervical carcinoma cell lines of high risk HPV subtypes .Methods HeLa (HPV-18-positive) and Caski (HPV-16-positive) cells were incubated with different concentrations of SeO 2 for 24 h respectively.Mor-phological changes of HeLa and Caski cells were observed under inverted optical microscope ;cell proliferation and activity were examined by MTT assay;flow cytometry was employed to detect the cell apoptosis;the expressions of apoptosis-related proteins caspase-3 and p53 in cervical carcinoma cell lines were determined by Western blot analysis;the effects of SeO 2 on apoptosis-related miRNA LET-7a expression was detected by stem-loop reverse tran-scription-polymerase chain reaction (RT-PCR).Results Cell morphology was obviously changed in vitro.Cells be-came rounded and shrunken .SeO2 markedly inhibited cell proliferation and viability in a dose-dependent manner in both cell lines; In HeLa cells the inhibitory effects induced by 7.5-30 μmol/L of SeO 2 were significant ( P<0.05);The inhibitory effects on Caski were statistical significant (P<0.05) even with low concentrations of SeO 2. The apoptosis induced by SeO 2 increased dose-dependently in cervical carcinoma cell lines , which were higher in Caski.SeO2 up-regulated the apoptosis-related proteins in cervical carcinoma cell lines .The expressions of caspase-3 and p53 in HeLa cells both significantly increased as compared with control group (P<0.05), and peaked at the concentration of 7.5 μmol/L.Treated with higher concentrations ( 7.5-30 μmol/L ) of SeO 2 , the expression on Caski cells increased significantly ( P<0.05 ) .SeO 2 induced of expression of apoptosis-related miRNA LET-7a both in HeLa cells and Caski cells with statistical meanings ( P<0.05 );the effects reached its peak at the concentration of 7.5 μmol/L bothly.Conclusions SeO2 shows anti-tumor properties via apoptosis pathway by up-regulating the expressions of apoptosis-related proteins caspase-3, the mechanisms of can be potentially explained by p 53 and LET-7a in cervical cancer cell lines.The apoptosis-inducing effect of SeO2 is more sensitive in HPV16+cell line compared with HPV18+cell line.