AIM: To study the effects of naringenin eye drops on NaIO3-induced retinal pigment epithelium (RPE) degeneration and laser-induced choroidal neovascularization (CNV) in rat eyes.METHODS: The 35mg/kg NaIO3-induced RPE degeneration was prevented by 10g/L naringenin eye drops 3 times a day for 7 days in advance of NaIO3 injection, and then 2 to 4 weeks thereafter, RPE function was measured with C-wave of electroretinogram (ERG). The laser-induced CNV rats were treated with laser to break the Bruchs membrane and the CNV formation was prevented by 10g/L naringenin eye drops instilled 3 times a day for 2 to 4 weeks. The CNV formation was measured with fluorescein angiography (FA) and flat mount. RESULTS: Two weeks after NaIO3 injection, the amplitude of ERG C-wave fell markedly in NaIO3 group to 53% of normal group (P<0.01). No apparent difference was observed in naringenin+ NaIO3 group. Four weeks later, the NaIO3 group fell to 37% of normal group (P<0.01), while the naringenin+ NaIO3 group fell to only 57% of normal group (P<0.01). There is a 52% reversal of the ERG C-wave by naringenin as compared to NaIO3 treated group (P<0.05). Two weeks and four weeks after laser treatment, naringenin reduced the CNV formation to 53% and 49% of control group (100%) measured by FA (P<0.01). Four weeks after laser treatment, naringenin reduced the CNV formation by 47% as compared to control group measured with flat mount (P<0.01).CONCLUSION: Naringenin significantly protected RPE from NaIO3 induced degeneration and can also prevent CNV formation.

·AIM: To study the effects of 10g/L hydralazine eye drops on 35mg/kg NaIO3-induced degeneration in rat eyes. · METHODS: Various doses of NalO3 and/or saline alone were injected into Brown Norway rats from hypoglossal vein. After 3, 7, 14 or 28 days of injection, ERG a-, b-, c- wave, fast oscillation (FO) and light peak (LP) were measured along with retinal colored pictures and fluorescein angiography taken. Some rats were chosen to study the histology of retinas by light microscopy and autofluorescence of retina flatmounts. Different concen- trations of NaIO3 were given to RPE-19 cells, and cell proliferation rate was measured. For hydralazine study, 35mg/kg NaIO3 was injected into Brown Norway rat from hypoglossal vein. NaIO3 group was treated with saline alone after NaIO3 injection, 10g/L hydralazine + NaIO3 group was treated with 10g/L hydralazine eyedrops after NaIO3 injection whereas normal group was treated with saline alone without NalO3 injection. All eyedrops were instilled locally 3 times a day for 4 weeks and ERG c-wave was measured at the end of 2 and 4 weeks.· RESULTS: After NaIO3 administration, the amplitude of all ERG waves fell markedly in large dose groups at 30, 40 or 60mg/kg NaIO3. Not many changes were observed in groups treated with < 30mg/kg NaIO3. Some retinal necrosis appeared from 3 days post-injection (PI) in 30mg/kg NaIO3 group, which became more serious in larger dose groups or longer treatment time, but no apparent change was found in smaller dose groups. Similarly, on the retina flatmount, RPE monolayer showed necrosis from 3 days PI in the 30mg/kg NaIO3 and larger dose groups. On histological examination, no significant change was seen in 30mg/kg NaIO3 and lower concentration groups. In cell culture experiment, changes were found in RPE-19 cells proliferation rate with a concentration of NaIO3 at 30mg/L or higher. In hydralazine experiments, 4 weeks after injection of NaIO3, ERG c-wave fell markedly in NaIO3 group to 31% of control group (P < 0.01). The ERG c-wave of hydra- lazine + NaIO3 group fell only to 50% of control group (P<0.05). This was a 61% reversal of the c-wave of NaIO3 treated group. · CONCLUSION: RPE degeneration induced by NaIO3 was both dose and time dependent. Around 30 to 40 mg/kg NaIO3 would be the optimal to be used as a non-exudative age-related macular degeneration rat model. Hydralazine may postpone the development of non-exudative age- related macular degeneration.

Objective: Applying the proteomics technology to identify proteins differentially in serums of idiopathic pulmonary fibrosis patients and normal population. Methods: The study included serum samples from idiopathic pulmonary fibrosis group and normal controlled group with 30 cases of each, from the Second Hospital of Shandong University, between October 2014 and October 2015. Proteins differentially expressed in serums were quantified by the isobaric tags for relative and absolute quantization coupled with two-dimensional liquid chromatography/tandem mass spectrometry technology. The proteins were analyzed in terms of molecular function, cell location and biological processes for showing the key protein molecules which were related to the development of idiopathic pulmonary fibrosis. Results: A total of 490 kinds of proteins (with confidence coefficient above 95%) were identified by mass spectrometry and 25 kinds of differentially expressed proteins were found. Compared with the control group, we found 4 types of up-regulated proteins and 21 down-regulated ones in the serum of idiopathic pulmonary fibrosis patients. Data from the Gene ontology analysis showed that most differentially expressed proteins were in the extracellular region (92%) while pathway enrichment analysis showed that most proteins were involved in the complement and coagulation cascade pathway. Conclusion: Proteins related to the complement system coagulation cascade pathway, and the proteins function need to be further studied.
Biomarkers/metabolism* ; Blood Proteins/metabolism* ; Chromatography, Liquid/methods* ; Humans ; Idiopathic Pulmonary Fibrosis/metabolism* ; Proteins/metabolism* ; Proteomics/methods* ; Tandem Mass Spectrometry/methods*

Objective: To understand the survival of HIV/AIDS patients after receiving antiretroviral therapy for 10 year in Henan province and related factors. Methods: The database of national integrated management system of HIV/AIDS was used to collect the basic information and follow-up information of HIV/AIDS patients who received antiretroviral therapy between 2003 and 2005 in Henan province. Software SPSS 23.0 was used to analyze the patients' survival and related factors based on the life-table method and Cox proportional hazards model. Results: Among the 2 448 HIV/AIDS patients who started antiretroviral therapy during 2003-2005, the men accounted for 53.5%, and women accounted for 46.5%. Up to 70.1% of the patients were aged 40-59 years and 95.5% of the patients had blood borne infections. The patients were observed for 10 years after antiviral treatment, and 719 cases died from AIDS related diseases, with a mortality rate of 3.78/100 per year (719/19 010 per year). The cumulative survival rates of patients within 1-year, 3 years, 5 years and 10 years were 0.94, 0.86, 0.78, 0.69 respectively. Compared with the patients aged <40 years, the HRs of the patients aged 40-, 50-, 60- and ≥70 years were 1.417 (95%CI: 0.903-2.222), 1.834 (95%CI: 1.174-2.866), 2.422 (95%CI: 1.539-3.810) and 3.424 (95%CI: 2.053-5.709) respectively. Compared with patients with baseline CD(4+)T lymphocyte >350 unit/ul, the HRs of the patients with CD(4+)T lymphocyte <50 unit/μl, 50-199 unit/ul and 200-350 unit/ul were 7.105 (95%CI: 5.449-9.264), 4.175 (95%CI: 3.249-5.366) and 2.214 (95%CI: 1.691-2.900) respectively. Compared with the women, the HR of the men was 1.480 (95%CI: 1.273-1.172). Compared with the patients who received second line ART therapy, the HR of patients receiving no second line therapy was 11.923 (95%CI: 9.410-15.104). Conclusions: The cumulative survival rate the HIV/AIDS patients after 10 years of antiretroviral therapy reached 0.69 in Henan. Male, old age, low basic CD(4+)T lymphocyte count and receiving no second line therapy were the risk factors for long-term survival of AIDS patients.
Acquired Immunodeficiency Syndrome ; Adult ; Aged ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; China/epidemiology* ; Female ; HIV/drug effects* ; HIV Infections/mortality* ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Risk Factors ; Survival Analysis ; Survival Rate

AIM: To study the effects of Tetramethylpyrazine (TMP) on retinal pigment epithelium (RPE) degeneration, choroidal blood flow and oxidative stress of RPE cells.METHODS: The 35mg/kg NaIO3-induced RPE degeneration rat eyes was given 25μg 1% TMP eye drops 3 times a day for 7 days before NaIO3 injection, and then 2 to 4 weeks after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Colored microsphere technique was used for in vivo experiments to determine the choroidal blood flow in ocular hypertensive (40mmHg) rabbit eyes. Methylthiazoltetrazolium (MTT) assay was used to study in vitro effect of TMP on various oxidants induced injury in the hRPE (ARPE-19 (ATCC, Manassas, VA, USA)) . RESULTS: Two weeks after NaIO3 injection, the amplitude of ERG c-wave fell markedly in NaIO3 group to 36% of control group (P<0.01). No apparent difference was observed in TMP+NaIO3 group. Four weeks later, the NaIO3 group fell to 46% of control group (P<0.01), while the TMP+NaIO3 group fell to only 77% of control group (P<0.01). There was a 67% reversal of the ERG c-wave by TMP as compared to NaIO3 group (P<0.01). The choroidal blood flow was significantly increased at all time points (at 30, 60 and 120 minutes after TMP instillation) as compared with corresponding controls. TMP had no effect on hypoxia-(1%O2), t-BHP- and H2O2-induced damage in RPE cells. 10μg/mL TMP could reverse 1 and 3mmol/L NaN3-induced loss of viability of RPE by 18.5% (P<0.01) and 23% (P<0.01), respectively. 30μg/mL TMP could reverse 30 and 100mmol/L NaIO3 induced loss of viability of RPE by 18.1% (P<0.05) and 16.8% (P<0.01), respectively.CONCLUSION: TMP can significantly protect RPE from NaIO3 induced degeneration in vivo and oxidative stress in vitro and can increase choroidal blood flow markedly in vivo .

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

Humans ; Osteogenesis ; Mesentery/surgery* ; Ossification, Heterotopic/surgery*

BACKGROUNDEpidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.

METHODSSix-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.

RESULTSUrine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.

CONCLUSIONAngiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; pathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Losartan ; therapeutic use ; Male ; Orchiectomy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole ; drug effects

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