Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

[A petition to American philanthropist for the donation of an American hospital in Tianjin].

At the dawn of the Republic of China, a group of doctors, educators, businessmen, officials, and the America returned Students in Tianjin jointly submitted a petition to American philanthropist for donation of a large-scale modern hospital. This petition, appended to a report to Carnegie Endowment for International Peace, has long been neglected by researchers. The memorandum may be informative to study local medical service at a transition period, and also helps understand the establishment and subsequent contribution of China Medical Board.

Factors Influencing Rust (Melampsora apocyni) Intensity on Cultivated and Wild Apocynum venetum in Altay Prefecture, China.

Rust (Melampsora apocyni) on Apocynum venetum is the major constraint to the commercial development of this medicinal herb. To determine the factors influencing rust intensity (maximum disease index [DImax]), rust was investigated from 2011 to 2015 in both cultivated and wild A. venetum plants. Partial least squares path modeling (PLS-PM) was used to analyze the paths and extent of the factors related to pathogen, environment, and host that affect rust intensity. DImax exhibited considerable variations across years and study sites, with variations linked to various factors fostering disease development. PLS-PM explained 80.0 and 70.1% of variations in DImax in cultivated and wild plants, respectively. Precipitation was the key factor determining DImax in both cultivated and wild plants (path coefficient [PC] = 0.313 and 0.544, respectively). In addition, the topsoil water content in cultivated plants and the total vegetation coverage in wild plants were also critical determinants of DImax via their effects on the microclimatic factor (contribution coefficients [CC] = 0.681 and 0.989, respectively; PC = 0.831 and 0.231, respectively). In both cultivated and wild plants, host factors were mainly dominated by A. venetum density (CC = 0.989 and 0.894, respectively), and their effect on DImax via the microclimatic factor (PC = 0.841 and 0.862, respectively) exceeded that via the inoculum factor (PC = 0.705 and 0.130, respectively). However, the indirect effects led to DImax variation, while the dilution effect on host (CC = 0.154) from weed in wild plants led to the indirect effect size in wild plants of 0.200, which was lower than -0.699 in cultivated plants.

Combined effects of oleic, linoleic and linolenic acids on lactation performance and the milk fatty acid profile in lactating dairy cows.

The potential combined effects of oleic, linoleic and linolenic acids supplementation on lactation performance and the milk fatty acid (FA) profile in dairy cows have not been well investigated. Our objective was to examine the effects of supplementation with a combination of these FA as well as the effects of removing each from the combination on lactation performance and the milk FA profile in dairy cows. Eight Holstein cows (101±11 days in milk) received four intravenously infused treatments in a 4×4 Latin square design, and each period lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery. The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively. The other three treatments were designated --C18 : 1 (20.68, 61.17 and 41.72 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively), -C18 : 2 (61.49, 19.55 and 42.13 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively) and -C18 : 3 (60.89, 60.16 and 1.53 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were not affected by the treatments, but the milk protein content was lower in cows treated with -C18 : 2 than that in CTL-treated cows. Milk yield as well as milk fat, protein and lactose yields were higher in cows treated with -C18 : 3 than the yields in CTL-treated cows, and these yields increased linearly as the unsaturation degree of the supplemental FA decreased. Compared with the CTL treatment, the -C18 : 2 treatment decreased milk C18 : 2 cis-9 content (by 2.80%) and yield (by 22.12 g/day), and the -C18 : 3 treatment decreased milk C18 : 3 cis-9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast, removing C18 : 1 cis-9 did not affect the milk content or yield of C18 : 1 cis-9. The -C18 : 2-treated cows had a higher C18 : 1 cis-9 content and tended to have a higher C18 : 1 cis-9 yield than CTL-treated cows. The yields of C8 : 0, C14 : 0 and C16 : 0 as well as

TRPV1 activation counters diet-induced obesity through sirtuin-1 activation and PRDM-16 deacetylation in brown adipose tissue.

BACKGROUND/OBJECTIVE: An imbalance between energy intake and expenditure leads to obesity. Increasing metabolism and thermogenesis in brown adipose tissue (BAT) can help in overcoming obesity. Here, we investigated the effect of activation of transient receptor potential vanilloid subfamily 1 (TRPV1) in the upregulation of thermogenic proteins in BAT to counter diet-induced obesity. SUBJECTS/METHODS: We investigated the effect of dietary supplementation of capsaicin (CAP) (TRPV1 agonist) on the expression of metabolically important thermogenic proteins in BAT of wild-type and TRPV1-/- mice that received either a normal chow or high-fat (±CAP; TRPV1 activator) diet by immunoblotting. We measured the metabolic activity, respiratory quotient and BAT lipolysis. RESULTS: CAP antagonized high-fat diet (HFD)-induced obesity without decreasing energy intake in mice. HFD suppressed TRPV1 expression and activity in BAT and CAP countered this effect. HFD-feeding caused glucose intolerance, hypercholesterolemia and decreased the plasma concentration of glucagon-like peptide-1 and CAP countered these effects. HFD suppressed the expression of metabolically important thermogenic genes, ucp-1, bmp8b, sirtuin-1 (SIRT-1), PPARγ coactivator 1α and PR domain containing zinc finger protein 16 (prdm-16) in BAT and CAP prevented this effect. CAP increased the phosphorylation of SIRT-1 and induced an interaction between peroxisome proliferator activated receptor gamma (PPARγ) with PRDM-16. Further, CAP treatment, in vitro, decreased the acetylation of PRDM-16, which was antagonized by inhibition of TRPV1 by capsazepine, chelation of intracellular Ca2+ by cell permeable BAPTA-AM or the inhibition of SIRT-1 by EX527. Further, CAP supplementation, post HFD, promoted weight loss and enhanced the respiratory exchange ratio. CAP did not have any effect in TRPV1-/- mice. CONCLUSIONS: Our data show that activation of TRPV1 in BAT enhances the expression of SIRT-1, which facilitates the deacetylation and interaction of PPARγ and PRDM-16. These data suggest that TRPV1 activation is a novel strategy to counter diet-induced obesity by enhancing metabolism and energy expenditure.

Effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats.

Andrographolide, which is one of the main pharmaceutical ingredients in traditional Chinese medicine Andrographis paniculata, can clear heat, detoxify human body, cool blood and reduce swelling, etc. Respiratory tract infectious diseases have been treated with the combination of andrographolide and theophyllines clinically. As andrographolide inhibits the CYP1A2 activity in vitro, it potentially interacts with theophyllines that are mainly metabolized by CYP1A2. Therefore, we herein studied the effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats. The blood drug concentrations of aminophylline, doxofylline and its metabolite theophylline were determined by HPLC. The theophylline AUC(0-t) was significantly elevated confronting the combination of andrographolide and aminophylline compared to that of the control group (P<0.05). Meanwhile, when only aminophylline was used, the theophylline clearance rate was significantly higher than those in the case of combination (P<0.05). The pharmacokinetics parameters of doxofylline and its metabolite theophylline in the individual administration group showed no significantly different from that combined with andrographolide. The results suggest that andrographolide and aminophylline should not be simultaneously administered because the former may raise the risks of side effects by inhibiting the clearance of the latter. In contrast, it is more secure to combine doxofylline with andrographolide owing to the almost intact pharmacokinetics.

Microsatellite markers for assessing genetic diversity of the medicinal plant Paris polyphylla var. chinensis (Trilliaceae).

Paris polyphylla var. chinensis is a perennial herb with medicinal properties that is widely used in traditional Chinese medicine. However, this plant has been on the edge of extinction during the last few decades because of excessive deforestation based on the intense ethnopharmaceutical interest. We isolated 12 microsatellite loci from a (CT)(n)-enriched genomic library of P. polyphylla var. chinensis. The polymorphism at each locus was analyzed by screening 30 individuals from a natural population. The number of alleles ranged from 2 to 5. The observed and expected heterozygosities ranged from 0.000 to 0.467, with a mean of 0.247, and from 0.383 to 0.662 with a mean of 0.537, respectively. Six loci (Pp1, Pp3, Pp6, Pp7, Pp9, and Pp12) were found to significantly deviate from Hardy-Weinberg equilibrium. This may be due to the small population size, inbreeding or null alleles. Five of the pairwise comparisons (Pp1 and Pp4, Pp2 and Pp5, Pp2 and Pp9, Pp2 and Pp12, Pp11 and Pp12) exhibited significant linkage disequilibrium (P < 0.05). We conclude that these microsatellite markers will be useful for population genetic studies of P. polyphylla var. chinensis.

Polymorphic microsatellite loci for the genetic analysis of Lycoris radiata (Amaryllidaceae) and cross-amplification in other congeneric species.

Lycoris radiata is a perennial herb that has been used in traditional Chinese medicine for a long time and has two main medicinal components in its bulb, lycorine and galanthamine. However, the original microsatellite loci have not been developed for any species of Lycoris. Total genomic DNA was extracted from fresh bulbs using a modified CTAB protocol. We isolated 10 microsatellite loci from 21 L. radiata individuals of a natural population from Yellow Mountain in Anhui Province, China. The number of alleles ranged from two to nine. The observed and expected heterozygosities ranged from 0.238 to 0.952 and from 0.455 to 0.784, respectively. One locus significantly deviated from Hardy-Weinberg equilibrium and no significant linkage disequilibrium was found between pairs of loci. Cross-species amplification of these microsatellite loci was characterized in additional five species (L. sprengeri, L. anhuiensis, L. albiflora, L. longituba, and L. chinensis) of Lycoris. The results suggest that these microsatellite markers would contribute to the population genetic studies of L. radiata and other related species.

Sorbic acid improves growth performance and regulates insulin-like growth factor system gene expression in swine.

Sorbic acid (SA) is a PUFA with a conjugated double bond. The conjugated fatty acids, including CLA, are multifunctional bioactive fatty acids with the ability to improve growth performance. The effect of SA on pig growth performance was examined to determine its mechanism of action. The ADG, ADFI, and serum IGF-I concentration were examined, as were IGF-I secretion and IGF system gene expression in hepatocytes. Two hundred forty 21-d-old Duroc × Landrace × Yorkshire weaned piglets (6.86 ± 0.02 kg) were randomly divided into 4 groups, each consisting of 3 pens of 20 piglets (10 female and 10 male). The 4 groups of piglets were kept in a temperature-controlled room (26 to 28 °C), and feed and water were provided to the pigs ad libitum. Weanling piglets were fed diets that included 0, 0.5, 2, or 4 g of SA/kg for 42 d. The diet supplemented with 0.5 g/kg of SA improved (P < 0.05) ADG, BW, and G:F, whereas supplementation with all 3 SA doses increased (P < 0.05) ADG and G:F at 21 to 42 d of age. The greatest concentration of plasma triglycerides was observed (P < 0.05) in the 4 g/kg of SA group. The SA increased (0.5 g of SA/kg, P > 0.05; 1 g of SA/kg, P < 0.05; and 2 g of SA/kg, P < 0.05, respectively) plasma total serum protein and globulin concentrations in a dose-dependent manner. It was noted that the smallest SA treatment dose (0.5 g/kg) dramatically increased (P < 0.05) serum IGF-I concentration but decreased (P < 0.05) the concentrations of blood urea N and cortisol. The SA increased (P < 0.05) IGF-I, IGF-II, IGF-I receptor (IGF-IR), and PPARα gene mRNA expression and IGF-I secretion, but not (P > 0.05) IGFBP or PPARγ mRNA expression, in pig primary hepatocytes. These results indicate that SA improves growth performance by regulating IGF system gene expression and hormone secretion.

Effect of bio-treatment on the lipophilic and hydrophilic extractives of wheat straw.

Wheat straw, an important papermaking raw material in China, was treated with a white-rot fungus of Phanerochaete chrysosporium ME446, and the lipophilic and hydrophilic extractives from the control and bio-treated samples were analyzed by GC and GC-MS. Bio-treatment of wheat straw could alter the chemical composition of both the lipophylic and hydrophilic extractives. Sugars and phenolic substances such as coniferyl alcohol, 4-hydroxycinnamic acid, 1-guaiacylglycerol and ferulic acid were substantially degraded or consumed by the fungus. More lipophilic substances such as wax, glycerides and steryl esters were degraded into the corresponding components, resulting in much higher concentrations of fatty acids and sterols in the bio-treated samples. Obviously, the bio-treatment of wheat straw was of benefit to pitch control in pulping and papermaking processes, in the view of degradation of the more lipophilic substances. In addition, the bio-treatment could increase the lignin concentration in hot-water extractives of wheat straw.

Effects of Astragalus polysaccharides and astragalosides on the phagocytosis of Mycobacterium tuberculosis by macrophages.

The herb Astragalus membranaceus is used in traditional Chinese medicine to boost immunity. This study investigated the effects of Astragalus polysaccharides (APS) and astragalosides (AS) on the phagocytosis of Mycobacterium tuberculosis by macrophages. Peritoneal macrophages were obtained by peritoneal lavage from mice stimulated by starch gravy culture medium and cultured with M. tuberculosis and varying concentrations of APS and AS. Phagocytotic activity was measured using a real-time polymerase chain reaction assay to detect M. tuberculosis DNA. Levels of interleukin-1beta, interleukin-6 and tumour necrosis factor-a secreted by activated macrophages in the culture supernatant were determined using an enzyme-linked immunosorbent assay. Macrophage phagocytotic activity and secreted cytokine levels were significantly increased after treatment with APS and AS. This study provides evidence that APS and AS have strong promoting effects on the phagocytosis of M. tuberculosis by macrophages and the secretion of interleukin-lbeta, interleukin-6 and tumour necrosis factor-alpha by activated macrophages.

Activity of the botanical aphicides 1,5-diphenyl-1-pentanone and 1,5-diphenyl-2-penten-1-one on two species of Aphididnae.

1,5-Diphenyl-1-pentanone (A) and 1,5-diphenyl-2-penten-1-one (B) are natural products extracted for the first time from Stellera chamaejasme. Laboratory bioassay showed that the two products have strong contact activity and very good anti-feedant activity against Aphis gossypii and Schizaphis graminum. Both products showed dose-dependent relationships for both forms of activity against the two aphids, the contact activity of B being about twice that of A. Both products were inferior to methomyl in contact activity but superior in anti-feedant activity against the two aphids. This is the first report of aphicidal activity in these two compounds, which may represent a new class of aphicide.

[Clinical observation on effect of Xianlong capsule in treating vascular dementia].

OBJECTIVE: To study the effect of Xianlong Capsule (XLC) in treating vascular dementia (VD) and to explore its therapeutic mechanism. METHODS: The criteria of learning and memory related cholinergic nerve system, oxygen free radical and nitrogen monoxide (NO) in 35 patients with VD treated with XLC and 33 patients treated with hydergine were observed and compared with the normal control group. RESULTS: XLC could lower the acetylcholine esterase activity, increase the acetylcholine content in erythrocytes and plasma and decrease the NO content. No toxic adverse reaction was found in the observation period. CONCLUSION: XLC has definite effect in treating VD in aged patients, the therapeutic mechanism may be related with the actions in strengthening cholinergic nerve system, improving oxygen free radical metabolism, regulating NO and relieving its excitatory neurotoxicity.

[Effect of haidonghua powder(HDHP) on hypothalamic obesity in rats].

OBJECTIVE: To study the effect of HDHP including Laminaria japonica Aresch. and Benincasa hispida(Thunb.) Cogn. etc. on antiobesity in rats with hypothalamic obesity. METHOD: A rat model of hypothalamic obesity induced by MSG was used and the relative indexes was observed. RESULT: HDHP(2.5 g.kg-1) could significantly reduce the Lee's index as well as the size of fat cells. HDHP did not influence the serum levels of T3 and T4, insulin and aldosterone, did not inhibited appetite not led to diarrhea. CONCLUSION: HDHP has the effect of anti-obesity, Without any influencing on the function of thyroid gland and metabolism of water and salt. The mechanism is related to the reduction of fat cell size and the accumulation of fat.

[Clinical study on effect of xianlong capsule on senile vascular dementia].

OBJECTIVE: To assess the efficacy of Xianlong Capsule (XLC) in treating the senile vascular dementia (VD). METHODS: Forty-six cases of VD were randomly divided into two groups. The XLC group (24 patients) were treated with XLC and the control group (22 patients) were treated with Hydergine. Mini-mental state examination (MMSE), Hamilton depression scale (HDS) marks and clinical symptoms were observed in different groups. RESULTS: XLC could markedly increase MMSE and HDS marks of VD patients. XLC had the effect of improving balance and gait ability of VD patients. CONCLUSION: XLC had certain effect on VD and its effect was better than that of Hydergine.

Regulation of thalamic neurite outgrowth by the Eph ligand ephrin-A5: implications in the development of thalamocortical projections.

The cerebral cortex is parcellated into different functional domains that receive distinct inputs from other cortical and subcortical regions. The molecular mechanisms underlying the specificity of connections of cortical afferents remain unclear. We report here that the Eph family tyrosine kinase receptor EphA5 and the ligand ephrin-A5 may play a key role in the exclusion of the limbic thalamic afferents from the sensorimotor cortex by mediating repulsive interactions. In situ hybridization shows that the EphA5 transcript is expressed at high levels in both cortical and subcortical limbic regions, including the frontal cortex, the subiculum, and the medial thalamic nuclei. In contrast, ephrin-A5 is transcribed abundantly in the sensorimotor cortex. Consistent with the complementary expression, the ligand inhibited dramatically the growth of neurites from neurons isolated from the medial thalamus but was permissive for the growth of neurites from lateral thalamic neurons, which is primarily nonlimbic. Similarly, the growth of neurites from Eph-A5-expressing neurons isolated from the subiculum was inhibited by ephrin-A5. Our studies suggest that the Eph family ligand ephrin-A5 serves as a general inhibitor of axonal growth from limbic neurons, which may serve to prevent innervation of inappropriate primary sensorimotor regions, thus contributing to the generation of specificity of thalamic cortical afferents.

Prevention of maternal-fetal blood group incompatibility with traditional Chinese herbal medicine.

OBJECTIVE: To evaluate the effect of traditional Chinese herbal medicine on the prevention of hemolytic disease caused by maternal-fetal blood group incompatibility. METHODS: A total of 126 Chinese patients with maternal-fetal blood group incompatibility were studied, including 105 cases of ABO type and 21 cases of Rh type incompatibility. The traditional Chinese herbal medicine was used for preventative treatment in 79 cases, and 47 cases served as controls. The prescription consisted of Herba leonuri 500 g, white peony root 180 g, Banksia rose 12 g, root of Chinese angelica 150 g and Rhizomal ligustica 150 g. RESULTS: Preventative treatment with traditional Chinese herbal medicine significantly reduced the perinatal mortality rate in cases of Rh type incompatibility, from 50.0% in the control group to 7.7% in the treatment group (P < 0.05). There was no death in the cases of ABO incompatibility. The traditional Chinese herbal medicine also decreased the degree of hemolysis. The percentage of severe cases in the control group was 29.8%, while it was 15.2% in the treatment group (P = 0.05). The duration of treatment was closely related to the outcomes. In patients who used traditional Chinese herbal medicine for more than 10 weeks, the incidence of severe hemolysis was 8.2%, compared with 38.9% in those treated for less than 10 weeks (P < 0.05). The change of serum immune antibody (A and/or B) titers during the treatment was a very important predictive factor for the outcome of the pregnancy. CONCLUSION: Traditional Chinese herbal medicine is effective not only for ABO type but also for Rh type maternal-fetal blood group incompatibility, with no side effects.

[Clinical study on the effect of shuxuening tablet in treatment of coronary heart disease].

Shuxuening was made of extract of Folium Ginkgo, the Shuxuening tablet No. 2 was a pure extract and No. 1 was a crude extract. Forty-six coronary heart disease patients were divided randomly into two groups according to the ratio of 2:1, Shuxuening tablet No. 1 and No. 2 were given to the two groups respectively. Results showed that both of them could alleviate the symptom of angina, the total effective rate of 2 groups were 60.00% and 83.87%, there was no significant difference between the two groups. But for the angina of middle and severe degree, the total effective rate of No. 2 was 83.33%, while that of No. 1 was 33.33%, the difference was significant (P < 0.01). They could also improve the abnormal electrocardiogram, the total effective rate of two groups were 60.00% and 74.19%, no significant difference between them was found. The two drugs could decrease the blood lipid as well.

Production, characterization and application of the cellulase-free xylanase from Aspergillus niger.

The effects of carbon source on xylanase and cellulase production were studied. The extract of steam-exploded corn stover was found to be the best raw material for producing cellulase-free xylanase. The xylanolytic enzymes of Aspergillus niger An-76 were purified by chromatography, and the properties of the four purified components were analyzed. When the enzyme was used to treat the birch Kraft pulp, and followed by a subsequent CEH bleaching, a brightness of 6.8% SBD more than that of the untreated one using the same chlorine dosage, or a saving of nearly 50% of chlorine consumption with the same brightness, was realized.

[Clinical and laboratory studies of effect of longevity-antihypertensive-mixture on elderly hypertension with kidney deficiency].

UNLABELLED: Longevity-Antihypertensive-Mixture (LAM) is a Chinese herbal drug, which could tonify Kidney in treating the hypertension with Kidney Deficiency in aged patients. RESULTS: 302 patients were randomly divided into three group: The treated group was subdivided into group I (107 Kidney Yin Deficiency patients) and group II (96 non-Kidney Yin Deficiency cases) and group III (99, control group). After treatment of LAM for 8 weeks, the rate of normalizing the blood pressure was 92.52% in group I while in group II, it was 84.43%, the symptoms were also significantly alleviated, and in group III, the rate was 70.71% only. The aorta compliance in group I significantly improved after LAM treatment (P < 0.025), the quality index of left ventricle reduced in treated group, and there was significant difference between treated and control groups. After treatment, LAM could shorten the length of extracorporal thrombus in group. The study showed that LAM could treat hypertension through LAM, administration with good effect.