OBJECTIVEVasoconstriction and vascular hypersensitivity to serotonin were previously shown in animal models of adventitia injury. We investigated the contribution of angiotensin II (AngII)/AngII receptors and oxidative stress to vascular contractility and reactivity in this model.

METHODSWistar Kyoto rats were divided into 3 groups: normal (n = 6, no any intervention, only for measuring the serum AngII concentration), vehicle (n = 12, collared), and valsartan (n = 12, collared + valsartan 30 mg×kg(-1)×d(-1)). After one week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for one week. Blood flow and vascular reactivity to serotonin were determined one week after injury, the blood from left ventricle was taken to measure the serum AngII concentration by ELISA, and carotids were harvested for morphometry and Western blot analysis.

RESULTSAdventitia injury induced lumen cross-sectional area reduction (-44% vs. -5%), media diameter increase (62% vs. 10%), blood flow reduction [(2.79 ± 0.22) vs. (4.33 ± 0.84) ml/min] were significantly attenuated by valsartan. The increased vascular reactivity sensitivity to serotonin in vehicle group was also significantly reduced in valsartan group. Serum AngII concentration was significantly increased in vehicle group [(45.21 ± 4.52) pg/ml vs. (19.83 ± 0.5) pg/ml in normal rats, P = 0.0148] and the expression of AngII type 1 (AT(1)) receptor, AngII type 2 (AT(2)) receptor, as well as p22(phox) in collared arteries were significantly upregulated. Valsartan did not affect the AT(1) receptor expression but further increased serum AngII concentration [(89.73 ± 20.44) pg/ml vs. (45.21 ± 4.52) pg/ml, P = 0.001], and AT(2) receptor expression, while downregulated p22(phox) expressions.

CONCLUSIONSCollar-induced adventitia injury resulted in chronic vasoconstriction and vascular hypersensitivity to serotonin via increased serum AngII level, upregulated AngII receptors expression in the vascular well, and activated local oxidative stress. These changes could be blocked by valsartan suggesting a crucial role of AngII/AngII receptors on vascular contractility and reactivity changes in this model.

Angiotensin II ; metabolism ; Animals ; Carotid Arteries ; drug effects ; metabolism ; pathology ; Connective Tissue ; pathology ; Male ; Oxidative Stress ; Rats ; Rats, Inbred WKY ; Receptors, Angiotensin ; metabolism ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan ; Vasoconstriction ; drug effects

Objective To investigate the effects of panax notoginseng saponins (PNS) combined with total flavonoids from epimedium (TFE) on testicular dysfunction in natural aging rats; To discuss its mechanism of action. Methods Thirty 18-month old male SD rats were randomly divided into natural aging group, PNS combined with TFE low and high dose groups, with 10 rats in each group. Another 10 2-month old rats were set as young control group. PNS combined with TFE low and high dose groups were given gastric gavage of 10 mg/kg PNS combined with 10 mg/kg TFE, and 20 mg/kg PNS combined with 20 mg/kg TFE, respectively. Rats in young control group and natural aging group were given saline for 6 d each week, lasting for 4 months. Then, rats were sacrificed, and the testes were obtained to calculate the testicular weight and the testicular index. The testicular tissue morphology was observed by using HE staining. Testicular germ cell apoptosis was detected by using TUNEL method. The levels of Bcl-2, Bax and γ-H2 AX protein expression in testicular tissue were detected by Western blot. Results Compared with natural aging group, low and high dose of PNS combined with TFE significantly elevated the testicular weight and testicular index, improved the histological changes of testicular seminiferous tubule, significantly reduced number of apoptosis of spermatogenic cells in the testis, upregulated the expression of Bcl-2 protein in the testis, downregulated the expression of Bax and γ-H2 AX protein, and decreased the ratio of Bax/Bcl-2. Conclusion PNS combined with TFE can improve testicular dysfunction in natural aging rats by inhibiting apoptosis and DNA damage of germ cells.

OBJECTIVETo observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice.

METHODSFemale ICR mice began to be exposed to nano-alumina 10 d before mating, and the nano-alumina exposure lasted till offspring mice were born. All the female mice were randomly divided into 5 groups: solvent control group (saline), nano-carbon group (11.76 mg/ml), micro-alumina group (50 mg/ml), 50 nm alumina group (50 mg/ml), and 13 nm alumina group (50 mg/ml). All the mice were treated by nasal drip (10 µl/time) 3 times daily till offspring mice were born. Physiological indices, reflex and sensory function test, endurance test, Morris water maze test, positioning and navigation test, and open field test were used to evaluate the neurodevelopment of newborn mice.

RESULTSOn day 28, the body weight of 13 nm alumina group (16.73±4.04 g) was significantly lower than that of solvent control group (20.45±2.50 g) (P<0.01); the 13 nm alumina group had significantly delayed time to ear opening compared with the solvent control group (4.91±0.78 d vs 4.45±0.50 d, P<0.01); compared with the solvent control group, the nano-carbon group, micro-alumina group, 50 nm alumina group, and 13 nm alumina group had significantly delayed time to eruption of teeth (10.05±0.23 d vs 10.32±0.48 d, 10.75±0.45 d, 10.32±0.47 d, and 10.79±0.49 d, P<0.05 or P<0.01). On days 4 and 7 after birth, compared with the solvent control group, other groups had significantly decreased proportions of mice which passed the cliff avoidance test (P < 0.05 or P < 0.01). On days 12 and 14 after birth, compared with the solvent control group, the nano-carbon group, 50 nm alumina group, and 13 nm alumina group had significantly reduced pre-suspension time in the endurance test (P < 0.05 or P < 0.01). The Morris water maze and positioning and navigation tests showed that the 13 nm alumina group had a significantly increased 5 d incubation period compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of platform crossings (P < 0.05 or P < 0.01). The open field test showed that the nano-carbon group and 13 nm alumina group had reduced numbers of rearings compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of modifications (P < 0.01).

CONCLUSIONMaternal exposure to nano-alumina (13 nm) during pregnancy has inhibitory effects on the physical development and early behavioral development in newborn mice and can also inhibit the learning and memory abilities and adaptability to new environment in offspring mice. The neurodevelopmental toxicity of nano-alumina to newborn mice increases as the particle sizes of nano-alumina decrease, which has been demonstrated by the endurance test and number of rearings.

Aluminum Oxide ; toxicity ; Animals ; Animals, Newborn ; Behavior, Animal ; Body Weight ; Female ; Maternal Exposure ; Maze Learning ; Mice ; Mice, Inbred ICR ; Motor Activity ; Nanostructures ; toxicity ; Pregnancy

OBJECTIVETo estimate correlation between phonetically balanced maximum (PB max) and pure tone auditory threshold in auditory neuropathy (AN) patients.

METHODSOne hundred and six AN patients were identified using multiple criteria including PB max, a metric for speech recognition, pure tone auditory threshold, acoustic emission test, distortion products otoacoustic emission (DPOAE) and auditory brainstem response (ABR). SPSS statistical software was used to estimate the Pearson's correlation between PB max and pure tone auditory threshold and to test whether pure tone auditory threshold, or auditory configuration had a significant impact on PB max.

RESULTSEven the patients had the same or similar values for pure tone auditory threshold or auditory configuration, varied values of PB max were found in two hundreds and twelve ears for 106 patients. Analysis of the data for 106 patients revealed a negative correlation (r = -0. 602, P <0. 01) between PB max and pure tone auditory threshold, i. e. hearing loss at a mild relates to a lower PB max. By using analysis of variance (ANOVA) method, it was found that both pure tone auditory threshold and auditory configuration had a significant (P <0.01) impact on the patients' PB max.

CONCLUSIONSThis analysis implicated the promise and potential of pure tone auditory threshold and auditory configuration for predicting PB max of the AN patients, and improving the diagnosis of AN.

Adolescent ; Adult ; Audiometry, Pure-Tone ; Auditory Threshold ; Child ; Child, Preschool ; Female ; Humans ; Male ; Speech Perception ; Vestibulocochlear Nerve Diseases ; physiopathology ; Young Adult

Objective To assess the adherence,immunologic and survival responses in HIV-infected patients receiving free antiretroviral therapy (ART). Methods All adult HIV-infected patients in Wenxi county who started antiretroviral treatment (ART) between 01 July 2001 and 31 December 2006 and aged above 18 years were included in this study. Epidemiological survey and laboratory tests were performed before,0.5 months after, 1 months after, 2 months after and every 3 months after initiation of ART to recognize the adherence, efficacy (CD4+ T cell counts) and survival to the regimens. Results The median follow-up time period was 16.5 months (Interquartile: 15.5-20.8 months). At baseline, the median of CD4+ T cell counts were 154 cells/μl (Interquartile: 81-212 cells/μl). Treatment was effective in most of the patients, the CD4+ T cell count of patients increased after the initiation of ART. The maximum increase was recorded at month 3, from the median of 154 cells/μl to 220 cells/μl (P<0.001) ,and thereafter the count remained stable. When comparing with patients with baseline CD4+ T cell count≥100 cells/μl, those with baseline CD4+ T cell count < 100 cells/μl showed a higher mean increase in the first three months of treatment. The cumulative probability rates of remaining alive were 0.94,0.88 and 0.87 at 3,12,24 months, respectively. In multivariate Cox's proportional hazard models, after adjustment for the type ofinitial regimens (NVP vs. EFV/IDV), CD4+T cell count of less than 50 cells/μl (vs. 50 cells/μl or more) was strongly associated with death hazard ratio 0.21 (95% CI:0.06-0.68). Conclusion Our data showed that ART was effective for improving immunologic response of adult patients with HIV/AIDS. CD4+ T cell count at initiation was associated with survival time in patients starting ART,suggesting that monitoring of CD4+ T count should be strengthened to early initiate antiretroviral therapy for HIV-infected patients.

BACKGROUND: In recent years, genetic haploidentical peripheral blood stem cell transplantation has been gradually improved, and haploid allogeneic hematopoietic stem cell transplantation has become an important treatment choice for malignant hematopoietic disease. OBJECTIVE: To observe the clinical efficacy of genetic haploidentical peripheral blood stem cell transplantation for myelodysplastic syndrome. METHODS: The clinical data of 21 myelodysplastic syndrome cases undergoing genetic haploidentical peripheral blood stem cell transplantation were retrospectively analyzed. Modified BU/CY+ATG administration was performed as a pretreatment strategy for haploidentical peripheral blood stem cell transplantation, and the combined use of cyclosporine A+mycophenolate mofetil+short-range methotrexate±basiliximab was adopted to prevent graft-versus-host disease (GVHD). RESULTS AND CONCLUSION: (1) The 21 cases were followed for an median of 333 days (22-1 222 days), with 76% (16/21) infection of granulocyte lack period, 100% (21/21) neutrophil reconstruction, the median implantation time of 12 days (7-17 days), 81% (17/21) platelet engraftment, and the median implantation time of 14 days (7-68 days). (2) The accumulative incidence of GVHD was 52.4% (11/21), including 29% (6/21) of acute GVHD and 24% (5/21) of chronic GVHD. The incidence of hemorrhagic cystitis was 38.1% (8/21). The recurrence rate after transplantation was 4.8% (1/21). (3) The 2-year non-relapse mortality was 48% (10/21), and the 2-year disease-free survival rate was 46.8%. These results show that in the absence of HLA-identical related donors and unrelated donor, genetic haploidentical peripheral blood stem cell transplantation is a safe, effective, feasible and alternative treatment option for myelodysplastic syndrome.

Objective To determine the survival rate of HIV/AIDS patients after receiving free antiretroviral treatment in Dehong prefecture, Yunnan province. Methods A retrospective cohort analysis was conducted on all the HIV/AIDS patients aged over 16 years who had started antiretroviral treatment during January 2007 throughout December 2009 in Dehong prefecture.Results A total of 3103 HIV/AIDS patients had received antiretroviral treatment during the study period. Among them, the mean age was (36.0 ± 9.9) years and 62.4% were males. 66.2% of them were infected with HIV through heterosexual transmission, and the mean treatment follow-up time was 21.7 months. Most patients well complied with the treatment, i.e., the average times of not taking the medicine were less than 5 per month. The cumulative survival rate of antiretroviral treatment after 1, 2, 3, 4, and 5 years were 0.95, 0.94, 0.93, 0.92, and 0.92, respectively. Data from the Cox proportional hazard regression model analysis indicated that, after adjustment for age, gender, and marital status, the baseline CD4+T cell counts and transmission route could significantly predicate the rates of survival. Those who were with baseline CD4+T cell counts as 200-350/mm3 were less likely to die of AIDS than those with CD4+T cell counts ＜200/mm3 (Hazard Ratio or HR=0.16, 95%CI:0.09-0.28), and HIV-infected through mother-to-child transmission or routes other than heterosexual transmission were less likely to die of AIDS than through injecting drug use (HR=0.35, 95% CI:0.13-1.00). Conclusion Free antiretroviral treatment had significantly improved the survival of HIV/AIDS patients. Earlier initiation of antiretroviral treatment was likely to have achieved better survival effects.

Objective To understand the prevalence of HIV infection and its influencing factors in the premarital physical examination population in Dehong Prefecture, Yunnan Province, 2017. Methods The data of people receiving premarital medical examination was collected, the demographic characteristics was described and the related factors was analyzed by Logistic regression. Results There were 21 875 participants receiving premarital medical examination in Dehong. 98(0.45%) participants were confirmed positive for HIV and male infection rate was 0.47% (52/10 955) and female was 0.42% (46/10 920). Among the 98 patients, 20 patients were infected in the first time, and main route was sexual transmission accounting for 81.63% (80/98). Logistic multivariate regression analysis showed that age, ethnicity and drug use were the influencing factors for premarital couples infecting HIV. The risk of HIV infection in 31-40 and 41-50 years old group was higher than the people under 25 years old group(OR=3.78, 95% CI：1.81-7.89, P<0.001；OR=3.95, 95% CI：1.72-9.08, P=0.001). The infection risk of Dai and Jingpo ethnic group was higher than that of the Han ethnic(OR=1.86, 95% CI：1.06-3.29, P=0.031；OR=3.25, 95% CI：1.81-5.84, P<0.001). The risk of infection among drug users was much higher than non-drug users (OR=926.76, 95% CI：271.65-3 161.71, P<0.001). Conclusion Age, ethnicity, and drug use are influencing factors of HIV infection among premarital couples. Targeted measures need to be taken against risk factors. HIV infection is mainly transmitted by sexual transmission. It can be effectively detected and controlled through premarital medical examination.

To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1， 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.

Objective: To explore the effect and mechanism of Wuzi Yanzong Fang (WZ) on proliferation of spermatogonial stem cells in aging rats by regulating miR-let-7-Imp axis.Method: A total of 40 18-month-old male SD rats were randomly divided into aging model group, and low, middle and high-dose WZ groups, with 10 rats in each group. Ten 2-month old rats were used as young control group. Low, middle and high-dose WZ groups were given by gastric WZ 0.4, 0.8, 1.6 g·kg^-1 respectively. Young control group and aging model group were given normal saline for 4 months, which was suspended for 2 days every week. Rats were put to death after the final treatment with WZ, and then the testes were quickly removed from rats. The relative mRNA expression levels of miR-let-7 and Imp were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expressions and localization of p-JAK2/JAK2, phosphate(p)-signal transduction and transcriptional activators3 (STAT3)/STAT3 signaling pathway proteins were detected by Western blot and immunofluorescence. The numbers of spermatogonial stem cells and the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunofluorescence. The testicular tissue morphology was observed using htoxylin eosin (HE) staining.Result: Compared with young control group, the expression levels of miR-let-7 mRNA were significantly increased, while the expression levels of Imp mRNA were decreased in the aging model group(P<0.01). Conversely, the expression levels of miR-let-7 mRNA were significantly decreased (P<0.05, P<0.01), while the mRNA expression levels of Imp mRNA were significantly increased after WZ treatment(P<0.05). The results of Western blotting and immunofluorescence showed that the expression levels of p-JAK2, p-STAT3 in aging model group were decreased significantly(P<0.01), while WZ significantly increased the expression levels of p-JAK2, p-STAT3(P<0.05, P<0.01). Immunofluorescence results showed that compared with young control group, the number of spermatogonial stem cells and PCNA expression decreased in aging model group. After WZ treatment, the number of spermatogonial stem cells was increased, whereas PCNA expression was up-regulated. HE showed that WZ significantly improved the testicular tissue structure of aging rats.Conclusion: WZ effectively promote the proliferation of spermatogonial stem cells by regulating miR-let-7-imp axis in testis.