AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation

OBJECTIVE: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. MATERIALS AND METHODS: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). RESULTS: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. CONCLUSION: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.
Adult ; Aged ; Carcinoma, Neuroendocrine/pathology/*radionuclide imaging/therapy ; Female ; Fluorodeoxyglucose F18/*diagnostic use ; Humans ; Middle Aged ; Radiopharmaceuticals/*diagnostic use ; Uterine Cervical Neoplasms/pathology/*radionuclide imaging/therapy ; Vaginal Neoplasms/pathology/*radionuclide imaging/therapy

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) are characterized by abnormal central processing with altered brain activation in response to visceral nociceptive signals. The effect of electroacupuncture (EA) on IBS patients is unclear. The study is set to study the effect of EA on brain activation during noxious rectal distension in IBS patients using a randomized sham-controlled model. METHODS: Thirty IBS-diarrhea patients were randomized to true electroacupuncture or sham acupuncture. Functional MRI was performed to evaluate cerebral activation at the following time points: (1) baseline when there was rectal distension only, (2) rectal distension during application of EA, (3) rectal distension after cessation of EA and (4) EA alone with no rectal distension. Group comparison was made under each condition using SPM5 program. RESULTS: Rectal distension induced significant activation of the anterior cingulated cortex, prefrontal cortex, thalamus, temporal regions and cerebellum at baseline. During and immediately after EA, increased cerebral activation from baseline was observed in the anterior cingulated cortex, bilateral prefrontal cortex, thalamus, temporal regions and right insula in both groups. However, true electroacupuncture led to significantly higher activation at right insula, as well as pulvinar and medial nucleus of the thalamus when compared to sham acupuncture. CONCLUSIONS: We postulate that acupuncture might have the potential effect of pain modulation in IBS by 2 actions: (1) modulation of serotonin pathway at insula and (2) modulation of mood and affection in higher cortical center via ascending pathway at the pulvinar and medial nucleus of the thalamus.
Acupuncture ; Acupuncture Therapy ; Brain ; Cerebellum ; Electroacupuncture ; Humans ; Irritable Bowel Syndrome ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Neural Pathways ; Pain Perception ; Prefrontal Cortex ; Pulvinar ; Salicylamides ; Serotonin ; Thalamus

Objective: To understand the characteristics of HIV infected persons without long term disease progress [also known as long term non-progressors (LTNPs)], and related factors in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data of persons living with HIV and receiving no antiretroviral therapy in Guangxi by the end of 2016 were collected from the national HIV/AIDS comprehensive control and prevention information system of China. Results: By the end of 2016, there were 313 LTNPs in Guangxi, accounting for 2.3% of those being reported for more than 10 years, 5.4% of those being reported for more than 10 years and surviving, and 26.6% of those being reported for more than 10 years, surviving and receiving no antiretroviral therapy. Among the LTNPs, 87.2%(273) were men, 94.9% (297) were aged ≤ 40 years, 32.3% (101) were farmers, 55.6% (174) were single, divorced or widowed, 69.3% (217) were of Han ethnic group, 68.1% (213) were injecting drug users, and 52.1% (163) were from custody facilities. Multiple logistic regression analysis indicated that factors associated with delayed disease progression included age ≤40 years (compared with age >40 years, aOR=1.55, 95%CI: 1.31-3.12) and injection drug use (compared with sexual transmission, aOR=1.23, 95%CI: 1.10-1.74). Conclusions: A number of LTNPs existed in HIV-infected individuals in Guangxi. Further research are needed to identify the related factors, and it is necessary to conduct large sample size studies on host immunology, genetics and the virology of HIV to explore the related mechanism.
Adolescent ; Adult ; Age Distribution ; China/epidemiology* ; Drug Users/statistics & numerical data* ; Ethnicity/statistics & numerical data* ; HIV Infections/ethnology* ; Humans ; Male ; Socioeconomic Factors

INTRODUCTIONThe 2005 American Association for Study of Liver Diseases (AASLD) diagnostic criteria allow non-invasive diagnosis of hepatocellular carcinoma (HCC) based on their enhancement pattern but we have observed a high incidence of atypical enhancement characteristics in HCC associated with portal vein thrombosis. This study seeks to examine the radiological features of this particular subgroup.

MATERIALS AND METHODSPatients with HCC and portal vein thrombosis who underwent pre-treatment multiphasic CT imaging were drawn from a surgical database. The arterial, portal venous and delayed phase images were assessed qualitatively and quantitatively (with region of interest [ROI] analysis) for lesion hypervascularity and washout. The background enhancement of the left and right lobes of the liver was also quantifi ed by ROI analysis.

RESULTSTwenty-fi ve lesions in 25 patients were selected for analysis. Qualitative analysis showed that 10/25 (40%) lesions demonstrated arterial hypervascularity while 16/25 (64%) lesions showed washout. Ten out of 25 (40%) lesions demonstrated both arterial hypervascularity and washout. Quantitative analysis showed that the average absolute lesion enhancement from precontrast to arterial phases was 49.1 (± 17.1) HU for hypervascular lesions compared to 23.8 (± 16.6) HU for non-hypervascular lesions (P <0.01). The mean absolute enhancement of the background liver parenchyma in the arterial phase was 13.79 (± 7.9) HU for hypervascular lesions compared to 36.6 (± 30.6) HU for non-hypervascular lesions (P = 0.03).

CONCLUSIONA large proportion of HCC with portal vein thrombosis lack characteristic arterial hypervascularity, which may be secondary to compensatory increased arterial supply to the background liver. This is a potential pitfall when applying imaging criteria for diagnosis of HCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; complications ; diagnostic imaging ; Female ; Humans ; Liver Neoplasms ; complications ; diagnostic imaging ; Male ; Middle Aged ; Pattern Recognition, Automated ; Portal Vein ; diagnostic imaging ; physiopathology ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Venous Thrombosis ; diagnostic imaging ; etiology

OBJECTIVETo investigate the effects of artificial ligand of peroxisome proliferators activated receptors (PPARs), rosiglitazone (RGZ) and all trans-retinoic acid (ATRA) on human myeloma cell line growth in vitro and in vivo.

METHODSU266 and RPMI 8226 cells were treated with different concentration of RGZ in the presence or absence of ATRA and the results were studied by 3H-TdR thymidine incorporation (for cells proliferation), Annexin V-PI staining and caspase-3 activity assay (for cells apoptosis), RT-PCR (for FLIP, XIAP and survivin mRNA expression), and tumor formation test in BALB/c nude mice.

RESULTSExposure to RGZ induced proliferation inhibition in a dose-dependent manner in both U266 (r = 0.991, P < 0.01) and RPMI 8226 cells (r = 0.961, P < 0.01). A combination of RGZ with ATRA could enhance the inhibition effect (P < 0.001 in U266, P < 0.01 in RPMI8226). 10 micromol/L of RGZ induced apoptosis of (9.8 +/- 1.7)% in U266 cells and (10.7 +/- 3.3)% in RPMI8226 cells, in a time and dose dependent manner and combined with ATRA intensified the apoptosis induction effects (P < 0.01 in both cell lines). The FLIP, XIAP and survivin mRNAs were expressed in both cell lines and their levels decreased significantly after cultured with RGZ. The addition of RGZ + ATRA in the culture further decreased the levels. Caspase-3 activity increased substantially with the increase of RGZ concentration and the addition of RGZ + ATRA in the culture medium showed similar synergism effect on caspase-3 activation (P < 0.01). The xenograft of U266 cells in BALB/c nude mice were inhibited by RGZ and so did more by the combination of RGZ and ATRA (P < 0.01).

CONCLUSIONThe down-regulation of FLIP, XIAP and Survivin induced by RGZ can activate caspase-3, whereby induced apoptosis and proliferation inhibition in myeloma cells. ATRA can enhance these effects of RGZ.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Multiple Myeloma ; metabolism ; pathology ; Signal Transduction ; drug effects ; Thiazolidinediones ; pharmacology ; Tretinoin ; pharmacology

OBJECTIVETo investigate the effects of PPARgamma ligand (rosiglitazone, RGZ) as well as combined with all trans-retinoic acid (ATRA) on human myeloma cells and try to explore the possible mechanism.

METHODSHuman myeloma cell lines U266 and RPMI-8226 cells were treated with RGZ in the presence or absence of ATRA. Cell proliferation was evaluated by [(3)H] thymidine incorporation, cell cycle distribution and CD49e expression were analyzed by flow cytometry, morphology changes were evaluated by Wright-Giemsa staining, and p27(Kip1) and p21(Waf1) expression was detected by Western blotting.

RESULTSThe exposure to RGZ induced proliferation inhibition in both cell lines in a dose-dependent manner. After cultured with 5 micromol/L RGZ, the proportion of U266 and RPMI-8226 cells in phase G(0)/G(1) was (45.2 +/- 6.7)% and (40.3 +/- 7.3)%, respectively (P < 0.05). The proportion of the cells in phase G(2)/M and S was (52.2 +/- 7.4)% and (57.4 +/- 9.5)%, respectively (P < 0.05). These changes were more evident when the RGZ concentration was increased to 10 micromol/L. A combination of RGZ with ATRA enhanced the growth inhibition and cell cycle arrest effects of RGZ. The RGZ-treated myeloma cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when RGZ was combined with ATRA. These changes were confirmed by the detection of CD49e expression. The expression of p27(Kip1) and p21(Waf1) in myeloma cells was up-regulated by RGZ and this change was more apparent when RGZ was used in combination with ATRA.

CONCLUSIONRGZ can induce cell cycle arrest and cell differentiation in myeloma cells which maybe caused by up-regulation of p27(Kip1) and p21(Waf1) expression. ATRA can enhance these effects of RGZ on multiple myeloma cells and combined use of these two drugs may show a synergistic effect on myeloma cells.

Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Integrin alpha5 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; PPAR gamma ; agonists ; Thiazolidinediones ; administration & dosage ; pharmacology ; Tretinoin ; pharmacology ; Up-Regulation

Objective: To analyze the effect of the identification and evaluation of Escherichia (E.) coli and Shigella, based on the upstream flanking sequences of CRISPR1. Methods: Both CRISPR and cas sequences were obtained through the BLAST with repeating sequences against the publicly complete genome in GenBank that related to E. coli and Shigella. Clustal X was used to perform multi-sequences alignment of the flanking sequences. PCR method was used to amplify the upstream flanking sequences of CRISPR1 in order to appraise the effect of identification and evaluation of upstream flanking sequences on E. coli and Shigella, which were based on the upstream flanking sequences of CRISPR1. Results: The results showed that 73.4% of the strains containing the I-E CRISPR/Cas that belonged to the phylogroups A, B1, D while 8.4% strains carried the I-F CRISPR/Cas. Another 17.2% of the strains owned CRISPR3-4 (non-CRISPR/Cas) only belonged to the phylogroups B2. All the Shigella strains carried I-E CRISPR/Cas. More than 99% of similarity the CRISPR1 upstream-flanking sequences was seen in E. coli (except B2) and Shigella and E. coli (B2). Both sensitivity and specificity were greater than 91% after PCR amplification in the region to identify the E.coli and Shigella. Conclusion: The upstream of CRISPR1 could achieve a preliminary identification effect on E.coli and Shigella.
Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; DNA, Bacterial/genetics* ; Escherichia coli/isolation & purification* ; Genotype ; Humans ; Molecular Sequence Data ; Sequence Analysis, DNA ; Shigella/isolation & purification*

Chronic constipation (CC) may impact on quality of life. There is substantial patient dissatisfaction; possible reasons are failure to recognize underlying constipation, inappropriate dietary advice and inadequate treatment. The aim of these practical guidelines intended for primary care physicians, and which are based on Asian perspectives, is to provide an approach to CC that is relevant to the existing health-care infrastructure. Physicians should not rely on infrequent bowel movements to diagnose CC as many patients have one or more bowel movement a day. More commonly, patients present with hard stool, straining, incomplete feeling, bloating and other dyspeptic symptoms. Physicians should consider CC in these situations and when patients are found to use laxative containing supplements. In the absence of alarm features physicians may start with a 2-4 week therapeutic trial of available pharmacological agents including osmotic, stimulant and enterokinetic agents. Where safe to do so, physicians should consider regular (as opposed to on demand dosing), combination treatment and continuous treatment for at least 4 weeks. If patients do not achieve satisfactory response, they should be referred to tertiary centers for physiological evaluation of colonic transit and pelvic floor function. Surgical referral is a last resort, which should be considered only after a thorough physiological and psychological evaluation.
Asia ; Asian Continental Ancestry Group ; Colon ; Constipation ; Health Resorts ; Humans ; Pelvic Floor ; Physicians, Primary Care ; Primary Health Care ; Quality of Life ; Referral and Consultation ; Sprains and Strains

OBJECTIVETo observe the effect of rosiglitazone (RGZ) and all-trans-retinoic acid (ATRA) on the growth of myeloma xenograft in nude mice and to explore the influence of RGZ and ATRA on VEGF expression and angiogenesis in the tumor.

METHODSVEGF gene expression in myeloma cell line U266 cells was analyzed by semi-quantitative RT-PCR after incubation with RGZ, ATRA, or RGZ + ATRA for 24 h. Myeloma xenograft was established by subcutaneous injection of 10(7) U266 cells in the scapula area of 4-week old nude mice. 7 days later, the nude mice were administered with RGZ, ATRA or RGZ + ATRA, respectively, by intraperitoneal injection once every day for 21 days. The control mice were given equal volume of normal saline instead of the drug. On the 21(st) day of treatment, the mice were sacrificed and the tumors were taken off, and the tumor volume and weight were measured. The tumors were examined by histopathology with HE staining, and microvessel density (MVD), CD34 and VEGF expression in the tumors were analyzed by immunohistochemical staining.

RESULTSVEGF mRNA was highly expressed in U266 cells and was decreased in a dose-dependent manner after incubation with RGZ. The VEGF mRNA level was further more decreased after RGZ + ATRA treatment. Xenografts of U266 cells were developed in all nude mice. The volume and weight of xenografts in the RGZ group were (785 ± 262) mm(3) and (1748 ± 365) mg, respectively, significantly lower than those of the control group (both P < 0.01). More significant inhibition was in the RGZ + ATRA group, (154 ± 89) mm(3) and (626 ± 102) mg, respectively, both were P < 0.05 vs. the RGZ group. RGZ inhibited the angiogenesis in U266 xenografts and immunohistochemical staining showed that the tumor MVD and VEGF expression were significantly decreased by RGZ treatment, and further more inhibited in the RGZ + ATRA group. VEGF protein was expressed in all xenografts in the nude mice. Its immunohistochemical staining intensity was 2.20 ± 0.40 in the control group, significantly higher than that of 1.48 ± 0.37 in the RGZ group (P < 0.01), and that of RGZ + ATRA group was 0.58 ± 0.26, further significantly lower than that of the RGZ group (P < 0.01). CD34 was expressed in all xenografts, most highly in the control group and lowest in the RGZ + ATRA group. The microvessel density (MVD) was highest in the control group (56.4 ± 15.2), significantly lower in the RGZ group (44.6 ± 11.2) (P < 0.05), and lowest in the RGZ + ATRA group (21.5 ± 8.6, P < 0.01).

CONCLUSIONSThe growth of myeloma cells can also be inhibited by RGZ and ATRA in nude mice in vivo. In addition to differentiation and apoptosis induction, RGZ can inhibit the formation of myeloma xenograft probably also through the downregulation of VEGF expression and subsequent angiogenesis.

Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Transplantation ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Thiazolidinediones ; administration & dosage ; pharmacology ; Tretinoin ; pharmacology ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays