Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity.

Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 µg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment protected against LPS-induced fetal death. In addition, OCA pretreatment alleviated LPS-induced reduction of fetal weight and crown-rump length. Additional experiments showed that OCA inhibited LPS-evoked TNF-α in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-α, Il-1ß, IL-6, Il-12, Mip-2, Kc, and Mcp-1 By contrast, OCA elevated anti-inflammatory cytokine IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed that OCA blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth zone. These results provide a mechanistic explanation for placental FXR-mediated anti-inflammatory activity. Overall, this study provides evidence for roles of FXR as an important regulator of placental inflammation.

Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters.

Effectiveness of strengthened stimulation during acupuncture for the treatment of Bell palsy: a randomized controlled trial.

BACKGROUND: The traditional Chinese theory of acupuncture emphasizes that the intensity of acupuncture must reach a threshold to generate de qi, which is necessary to achieve the best therapeutic effect. De qi is an internal compound sensation of soreness, tingling, fullness, aching, cool, warmth and heaviness, and a radiating sensation at and around the acupoints. However, the notion that de qi must be achieved for maximum benefit has not been confirmed by modern scientific evidence. METHODS: We performed a prospective multicentre randomized controlled trial involving patients with Bell palsy. Patients were randomly assigned to the de qi (n = 167) or control (n = 171) group. Both groups received acupuncture: in the de qi group, the needles were manipulated manually until de qi was reached, whereas in the control group, the needles were inserted without any manipulation. All patients received prednisone as a basic treatment. The primary outcome was facial nerve function at month 6. We also assessed disability and quality of life 6 months after randomization. RESULTS: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR] 4.16, 95% confidence interval [CI] 2.23-7.78), better disability assessment (differences of least squares means 9.80, 95% CI 6.29-13.30) and better quality of life (differences of least squares means 29.86, 95% CI 22.33-37.38). Logistic regression analysis showed a positive effect of the de qi score on facial-nerve function (adjusted OR 1.07, 95% CI 1.04-1.09). INTERPRETATION: Among patients with Bell palsy, acupuncture with strong stimulation that elicited de qi had a greater therapeutic effect, and stronger intensity of de qi was associated with the better therapeutic effects. TRIAL REGISTRATION: Clinicaltrials.gov no. NCT00685789.

[Time-series analysis on relationship between air pollution and mortality from circulatory system diseases among registered residents in Chaoyang district of Beijing].

OBJECTIVE: This study aims to investigate relationship between daily concentration of PM(10), SO(2), NO(2) and daily mortality due to circulatory system diseases in Chaoyang district, Beijing. METHODS: The time-series data of daily mortality from circulatory system diseases of registered residents in Chaoyang were obtained from Chaoyang District Center for Disease Control and Prevention. The daily concentration of sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and particulate matter (PM(10)) were collected from Beijing Municipal Environmental Monitoring Center. And the routine monitoring meteorological data were collected from Beijing Meteorological Bureau, including daily mean temperature and daily mean relative humidity. The time-series analysis was then conducted to determine the relationship of mortality from circulatory system diseases with daily concentrations of SO(2), NO(2) and PM(10) by using Poisson regression with generalized additive model (GAM). RESULTS: During January 2004 to September 2008, the cumulative death number from circulatory system diseases of registered residents in Chaoyang district of Beijing was 19 241, the daily average concentration of SO(2), NO(2), PM(10) was 48.7, 63.9, 146.1 µg/m(3), respectively. The single pollutant model showed an increase of daily concentration of PM(10), SO(2) and NO(2) by 10 µg/m(3) will augment the mortality from circulatory system diseases by 0.20% (95%CI: 0.01% - 0.39%), 0.36% (95%CI: -0.13% - 0.85%) and 0.30% (95%CI: -0.34% - 0.94%), respectively. In the multiple air pollutants models, combinatorial effects of PM(10) and SO(2) still positively correlated with increased mortality from circulatory system diseases (P < 0.05), whereas changes of the concentration of NO(2) had no significant effect on mortality from circulatory system diseases (P > 0.05). CONCLUSION: Our findings in this study elucidated that changes of the concentration of PM(10) and SO(2) had a positive correlation with daily mortality from circulatory system diseases among the local residents in Chaoyang District, whereas the daily concentration of NO(2) was irrelevant with that.

[Adsorption of Cd2+ from wastewater by modified fly ash.] / æ”¹æ€§ç²‰ç ¤ç°å¯¹åºŸæ°´ä¸­é•‰çš„å¸é™„ä½œç”¨.

The modified fly ash (MFA) was prepared through roasting the mixture of fly ash and NaOH/Ca(OH)2 at 250 ℃ for 1.5 h. The physicochemical properties of MFA were analyzed by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), X-ray diffraction (XRD), surface area analyze (BET), and Fourier transform infrared spectroscopy (FTIR) techniques. Results from BET analysis showed that the BET of MFA was enlarged by 20.6 times compared with FA. Results from SEM analysis showed that the glass phase was dissolved, with a rough surface and porous structure. Results from FTIR analysis demonstrated that -OH played an important role in Cd2+ adsorption. Results from the static adsorption experiment revealed that the removal efficiency of Cd2+ reached 97.3% when 0.2 g MFA was applied while the concentration of Cd2+ was 100 mg·L-1, the solution pH was 7.0, the adsorption temperature was 25 ℃ and the adsorption time was 90 min. In addition, the coexisting cations (K+, Na+, Mg2+, and Ca2+) might inhibit Cd2+ adsorption. Among all the cations, Ca2+ showed a most significant inhibitory effect on the removal of Cd2+. Langmuir isotherm and the pseudo-second-order kinetic models could well describe the adsorption behavior of Cd2+ on MFA, with the maximum adsorption capacity of 55.77 mg·g-1. Meanwhile, thermodynamic studies showed that Cd2+ adsorption onto MFA was spontaneous and endothermic process. MFA had better adsorption capacity than FA and had certain application pro-spects in wastewater treatment.

[Effects of cyclin dependent protein kinase inhibitor olomoucine on the microenvironment of axonal regeneration after spinal cord injury: an experiment with rats].

OBJECTIVE: To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the microenvironment of axonal regeneration after spinal cord injury (SCI). METHODS: Forty-five SD rats were randomly divided into 3 equal groups: SCI group undergoing SCI by hemisection technique and peritoneal injection of dimethyl sulfoxide (DMSO) solution 30 min after the SCI, SCI + olomoucine (SCI + Olo) group undergoing SCI by hemisection technique and peritoneal injection of olomoucine solution 30 min after the SCI, and sham operation group undergoing sham operation and peritoneal injection of DMSO solution 30 min after the operation. Three days after the operation the injured spinal cord segments of 5 rats from each group were taken out. Western blotting was used to detect the expression of the cell cycle related proteins, cyclin A, cyclin B, cyclin E, and proliferating cell nuclear antigen (PCNA). Immunofluorescence (IF) staining was used to detect the expression of glial fibrillary acidic protein (GFAP), growth associated protein-43 (GAP-43) and chondroitin sulphate proteoglycan (CSPG). Four weeks after the operation specimens of the injured spinal cord segment 15 mm in length were taken out from 5 rats in each group to undergo histological examination. The locomotion function of the hindlimbs was determined by modified Gale combined behavioral scoring (SBS) 1 day and 1, 2, 4, 6, and 8 weeks after the operation. RESULTS: Western blotting 3 days after the operation showed that the expressions of cyclin A, cyclin B, cyclin E, and PCNA were very weak in the sham operation group, were significantly increased in the SCI group, and were significantly down-regulated in the SCI + Olo group compared with those of the SCI group. IF staining showed that the number of astrocytes was small and the expressions of GFAP, CSPG, and GAP-43 were weak in the sham operation group; in the SCI group the astrocytic proliferation and glial scar was obvious, and the expressions of GFAP, CSPG, and GAP-43 were significantly increased compared with those of the sham operation group (all P < 0.05); and the astrocytic proliferation was significantly weaker and no obvious glial scar could be seen, and the expressions of GFAP and CSPG were weaker in the SCI + Olo group in comparison with the SCI group, however, the GAP-43 expression of the sham operation group was significantly increased compared with that of the sham operation group (P < 0.05). The hindlimbs of the SCI + Olo group and sham operation group were paralyzed without significant difference in the CBS values between these 2 groups, however, two weeks after the operation, the locomotion function scores at different time points of the SCI + Olo group were all significantly improved in comparison with that of the SCI group (all P < 0.05). CONCLUSION: Olomoucine promotes the recovery of the locomotion function of the paralyzed hindlimbs, probably through microenvironmental improvement of axonal regeneration by inhibiting the glial scar formation and CSPG secretion as well as upregulating the GAP-43 expression.

Needle Sensation and Personality Factors Influence Therapeutic Effect of Acupuncture for Treating Bell's Palsy: A Secondary Analysis of a Multicenter Randomized Controlled Trial.

BACKGROUND: It has not been solved what kind of needle sensation might influence outcomes of acupuncture treatment. Effects of personality factors on the therapeutic effect of acupuncture have not been investigated. This study aimed to find the effects of the traits of personality on the objective outcome when different acupuncture techniques were used in treating patients with Bell's palsy. METHODS: We performed a secondary analysis of a prospective multicenter randomized controlled trial of acupuncture for Bell's palsy. Patients were randomly assigned to the de qi and control groups, respectively. The primary outcome was facial nerve function at month 6. The intensity of each needle sensation was rated by a visual analog scale. Psychosocial factors were assessed by the pretreatment mediator questionnaire; 16 Personality Factor Questionnaire (16PF) was used for assessing personality factors and digit cancellation test for assessing attention. RESULTS: After 6 months, patients in the de qi group had better facial function (adjusted odds ratio [OR]: 4.16, 95% confidence interval [CI]: 2.23-7.78). Path analysis showed that intensity of needle sensation of fullness had direct effect on House-Brackmann (HB) score at month 6. In de qi group, the low HB score on day 1 (OR: 0.13, 95% CI: 0.03-0.45) and the low Social Boldness score (OR: 0.63, 95% CI: 0.41-0.97) in 16PF were associated with better facial function. In control group, low HB score on day 1 (OR: 0.25, 95% CI: 0.13-0.50), low Vigilance score (OR: 0.66, 95% CI: 0.50-0.88), and high Tension score (OR: 1.41, 95% CI: 1.12-1.77) in 16PF were related to better facial function. CONCLUSIONS: The needle sensation of fullness could predict better facial function and personality traits might influence outcomes of acupuncture treatment. Both of them should be considered seriously in acupuncture treatment and research.

Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 µg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1ß, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.

Maternal serum cadmium level during pregnancy and its association with small for gestational age infants: a population-based birth cohort study.

The association between maternal cadmium (Cd) exposure during pregnancy and the increased risk of fetal growth restriction (FGR) remains controversial. The present study evaluated the association between maternal serum Cd level and risk of small for gestational age (SGA) infants in a Chinese population. The present study analyzed a subsample of the C-ABCS cohort that recruited 3254 eligible mother-and-singleton-offspring pairs. Maternal serum Cd level during pregnancy was measured by graphite furnace atomic absorption spectrometry. The rate and odds ratio (OR) for SGA infant were calculated. The rate for SGA infant was 10.6% among subjects with H-Cd (≥1.06 µg/L), significantly higher than 7.5% among subjects with L-Cd (<1.06 µg/L). OR was 1.45 (95% CI: 1.11, 1.90; P = 0.007) among subjects with H-Cd. Adjusted OR for SGA infants was 1.43 (95% CI: 1.09, 1.88; P = 0.007) among subjects with H-Cd. Taken together, we observe the fact that maternal Cd exposure at middle gestational stage, elevates the risk of SGA in contrast to early gestational stage. The present results might be interesting and worth more discussing, and guarantee to further studies.

Treatment of Benign Prostatic Hyperplasia by Ultrasound-Guided Botulinum Toxin Type A Injection.

The objective of the study was to determine the efficacy of ultrasound-guided botulinum toxin type A (BTX-A) injection in the treatment of benign prostatic hyperplasia (BPH). In the 32 patients clinically diagnosed with BPH, 200 IU BTX-A was injected into five points at the lateral and middle lobes of the prostate under the guidance of ultrasound using a balloon dilatational device. The international prostate symptom score, quality of life score, maximum flow rate, post-void residual urine volume, prostate-specific antigen, and prostate volume were determined before treatment and at 1, 3, 6, and 12 months after treatment. All clinical symptoms and indicators were remarkably improved 1 month after the treatment and reached the optimal levels at 6 months post-treatment. This improvement of clinical parameters was maintained for a period of at least 1 year. Ultrasound-guided BTX-A injection was found to be safe and effective in the management of BPH.