[Association between cognitive impairment and main metals among oldest old aged 80 years and over in China].

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 µg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Improved tenderness of beef from bulls supplemented with active dry yeast is related to matrix metalloproteinases and reduced oxidative stress.

Supplementing diets with active dry yeast (ADY, Saccharomyces cerevisiae) improves the carcass quality grade of beef cattle and the tenderness of beef. The relevant mechanisms have not been fully elucidated, but may be related to the effect of ADY on oxidative stress and the activity of matrix metalloproteinases (MMPs). To provide further insight into these mechanisms, this study evaluated the influence of ADY supplementation on growth performance, carcass traits, meat quality, concentrations of MMPs in serum (MMP-2, MMP-9 and MMP-13), oxidative stress indices and antioxidant capacity indices in beef cattle. Forty-six crossbred Simmental × Yanbian bulls (∼18 months of age, BW 436 ± 35 kg) participated in a 145-day finishing trial. ADY supplementation significantly improved marbling deposition, intramuscular fat content, and beef tenderness (P < 0.05); altered individual fatty acid proportions in the beef and increased saturated fatty acids while decreasing polyunsaturated fatty acids (P < 0.05); significantly decreased the abundance of reactive oxygen species in serum and meat; significantly increased the level of superoxide dismutase in meat (P < 0.05); tended to increase the level of catalase (P = 0.075) in serum and glutathione reductase (P = 0.066) in meat; and increased the secretion of MMPs. The improvement of beef tenderness following ADY supplementation of finishing bulls is related to the effects of ADY on the secretion of MMPs and the lowering of oxidative stress.

[Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years].

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Effects of organic zinc on tibia quality, mineral deposit, and metallothionein expression level of aged hens.

The study aimed to determine the effects of methionine hydroxy analog chelate zinc on the tibia quality, mineral deposit, apparent retention of nutrients, and liver metallothionein (MT) expression level of aged laying hens. A total of 960 layers (Hy-Line Grey, 57 wk old) were randomly assigned into 4 groups, and each group had 8 replicates of 30 hens. During the first 2 wk, groups were fed a basal diet without extra zinc (Zn: 35.08 mg/kg). During the ensuing 14 wk, 4 levels of Zn (inorganic Zn: 80 mg/kg; organic Zn: 20, 40, 80 mg/kg) were added to the diet. The results indicated that both the Zn source and level did influence tibia strength and calcium (Ca) and Zn concentrations of tibia (P < 0.05), whereas there were no differences in the copper (Cu) and phosphorus (P) concentrations of the tibia and the tibia length (P > 0.05). Moreover, dietary supplementation with 40 or 80 mg/kg of organic Zn showed higher Zn and Ca concentrations in the tibia and higher tibia strength. The Cu concentration in the liver showed no difference among the 4 treatments, whereas the Zn concentration in the liver increased with the increasing Zn level. The apparent retention of P, iron (Fe), and manganese (Mn) was not affected by the Zn level or source (P > 0.05). However, the organic Zn group increased the apparent retention of Cu, Zn, Ca, crude protein (CP), and energy, and the group supplemented with 40 or 80 mg/kg of organic Zn obtained significant effects (P < 0.05). Moreover, dietary supplementation with 40 or 80 mg/kg organic Zn increased the MT mRNA expression of the liver at week 72, whereas 20 mg/kg of organic Zn decreased it (P < 0.05). In conclusion, this study suggested that an optimum dietary (40 mg/kg) organic Zn level plays a key role in promoting the apparent retention of minerals and nutrients, trace element deposit, and MT mRNA expression.

Effects of methionine hydroxyl analog chelated zinc on laying performance, eggshell quality, eggshell mineral deposition, and activities of Zn-containing enzymes in aged laying hens.

The study aimed to determine the effects of methionine hydroxyl analog chelated zinc (MHA-Zn) on laying performance, eggshell quality and mineral deposits, and the activities of Zn-containing enzymes on aged laying hens. A total of 960 layers (Hy-Line Grey, 57 wk old) were fed a basal diet (Zn: 35.08 mg/kg) without extra zinc for 2 wk. During the ensuing 14 wk, birds were randomly divided into 4 groups according to body weight and laying rate, with 8 replicates per treatment, and each group had 8 replicates of 30 hens. Four levels of Zn (ZnSO4: 80 mg/kg; MHA-Zn: 20, 40, 80 mg/kg) were added to the diet, respectively. The results shown that dietary Zn did not affect laying rate, average egg weight, average daily feed intake, or feed conversion ratio (P > 0.05); however, compared to the inorganic group, dietary supplementation with 40 or 80 mg/kg MHA-Zn decreased broken egg rate significantly in the whole period (P < 0.05), while significantly increased eggshell weight in week 62 to 72, eggshell thickness and eggshell strength in wk 66 to 72, eggshell weight percent and eggshell density in week 62 to 72 (P < 0.05). Besides, dietary supplementation with different sources and levels of Zn did not affect ash concentration of eggshell (P > 0.05), whereas dietary supplementation with 80 mg/kg MHA-Zn improved the Zn and Ca concentrations of eggshells and carbonic anhydrase (CA) activity of liver, and 40 mg/kg MHA-Zn increased Zn concentration of liver (P < 0.05). Moreover, no significant differences in alkaline phosphatase activity were observed among the treatment groups (P > 0.05). Therefore, dietary supplementation with 40 mg/kg MHA-Zn can improve eggshell quality by promoting Ca deposition and CA activity.

[Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

Influence of dietary slow-release urea on growth performance, organ development and serum biochemical parameters of mutton sheep.

Eighty Dorper × thin-tailed Han cross-bred non-castrated male lambs [mean body weight (BW), 25.87 ± 1.06 kg] were randomly allocated to one of five different concentrations of slow-release urea (urea phosphate, UP). The feed consisted of an equal amount of concentrate diet and roughage; the concentrate feed was formulated to be isoenergetic and isonitrogenic and contained 0%, 1%, 2%, 4% and 8% UP (UP0.0, UP1.0, UP2.0, UP4.0 and UP8.0, respectively) as a replacement for soya bean meal. Feed intake, BW, average daily gain (ADG), feed utilisation efficiency (FUE), absolute and relative organ weights and biochemical and histopathological parameters were measured. Feed intake, BW, ADG and FUE significantly decreased in the group receiving UP8.0 (p < 0.05), but no difference was found among the other groups (p > 0.05). Quadratic equations were developed between the UP dosage in the concentrate feed and ADG or FUE (r2  = 0.973 for ADG and r2  = 0.761 for FUE) to determine the appropriate dosage of UP given the desire to maximise either ADG or FUE, the appropriate dosage (feed concentration) was calculated as 2.01% UP to achieve the greatest ADG or 2.13% UP to achieve the best FUE. The relative weight of the liver (% BW) in the UP2.0 groups was significantly greater than that of UP0.0 (p < 0.05), and the relative weight of the intestine in the UP8.0 was significantly greater than that of UP0.0 (p < 0.05); the relative weight of the carcass, heart, spleen, lung, kidney, rumen, reticulum, omasum and abomasum did not differ among treatments (p > 0.05). The UP8.0 treatment significantly increased serum phosphorus levels (p < 0.05) and decreased the levels of alkaline phosphatase, glucose and calcium (Ca) compared with the lower UP dosage (p < 0.05). No histopathological differences were found in either hepatic tissues or renal tissues among treatments. Dietary UP as a replacement for soya bean in concentrate feeds for mutton sheep should not exceed 4%, as higher dosing may cause malnutrition and mineral disorders.

Estrogenic effects of flavonoid components in Xiaoyao powder.

The objective of this study was to evaluate the estrogenic effects and mechanisms of three flavonoid components in Xiaoyao powder: quercetin, kaempferol, and isorhamnetin. The drugs were used to treat estrogen receptor (ER)-positive human breast cancer MCF-7 cells, and proliferation was measured using the MTT method. The expression of proteins and mRNA of the ER subtype were measured using western blotting and real time polymerase chain reaction. The quercetin (10(-2) µM, 10(-3) µM), kaempferol (100 µM, 10(-2) µM), and isorhamnetin (10(-3) µM) promoted the proliferation of MCF-7 cells, and the expression of ERα and ERß proteins and mRNA were all increased significantly (P < 0.05). These effects were reversed by treatment with 0.1 µM estrogen antagonist ICI182780. Three flavonoid components in Xiaoyao powder increased the expression of proteins and mRNA of ERα and ERß and promoted the proliferation of MCF-7 cells. These estrogenic effects were mediated by the ER.

Hypothalamic, feeding/arousal-related peptidergic projections to the paraventricular thalamic nucleus in the rat.

Based on the importance of paraventricular thalamic nucleus (PVT) as a relay station of energy balance, arousal, and food reward, we aimed in the present study to determine projection patterns of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and orexin (ORX)-ergic fibers to the PVT. First, the distribution of peptidergic axon terminals within the PVT was examined. NPY and CART terminals were confined within the boundary of the thalamic nucleus, exhibiting almost identical distribution. MCH terminals were rarely observed. In contrast, ORX terminals were as extensive as NPY/CART terminals, but spread into the peri-PVT region. Second, neuronal origin of feeding/arousal-related peptides projecting to the PVT was investigated. NPY neurons were observed in the medial subdivision of the arcuate nucleus (Arc), whereas CART cells were in the lateral Arc as well as other hypothalamic regions including the paraventricular hypothalamic nucleus, lateral hypothalamus (LH), dorsal hypothalamic area, and zona incerta. Both NPY- and CART-fiber projections to the PVT were bilateral; ipsilateral proportion was 54.0% ± 3.6% (n = 6) for NPY and 57.1% ± 2.5% (n = 6) for CART. The total number of CART neurons projecting to the PVT exceeded that of NPY cells; the ratio of labeled CART neurons to NPY cells was 2.4 ± 0.2 (n = 6). In contrast, ORX-ergic fiber projection to the PVT exhibited a slight ipsilateral dominance (62.7% ± 1.6%, n = 6), with majority of labeled cells located in the LH medial to the fornix (72.2% ± 2.3%, n = 6). Third, based on heavy projection from the PVT to the nucleus accumbens shell (NAcSh), the convergence of NPY and CART terminals on a single PVT neuron was identified; the proportion of labeled PVT neurons that received converging NPY/CART terminals compared with the total PVT neurons projecting to the NAcSh was 2.7% ± 0.6% (n = 3). Finally, PVT cells receiving NPY, CART, or ORX terminals provided divergent axon collaterals to NAcSh and medial prefrontal cortex. The present observations provided the anatomical evidence that the PVT might play an essential role in the integration of antagonistically-acting, feeding/arousal-related peptidergic inputs on their way to the cortical reward circuit.

Isolation and characterization of Bacillus subtilis strain BY-3, a thermophilic and efficient cellulase-producing bacterium on untreated plant biomass.

UNLABELLED: Bioconversion of biomass, particularly crop wastes, into biofuels is being developed as an alternative approach in meeting the high energy demand. In this study, a thermophilic bacterial strain BY-3 that exhibits cellulolytic potential was isolated from faecal samples of Tibetan pigs; this strain was identified as Bacillus subtilis. The strain can produce cellulase when grown on various substrates, including carboxymethyl cellulose, rice straw, corn stover, soluble starch and wheat bran. The maximum cellulase activity of the strain was up to 4·323 ± 0·065 U ml(-1) when cultivated in the medium containing corn stover (30 g l(-1) ) for 24 h. The results demonstrated that corn stover is the most suitable substrate for cellulase production by the strain BY-3. The crude cellulase of strain BY-3 was most active at pH 5·5 and 60°C, and the enzyme in acetate buffer (50 mmol l(-1) ) demonstrated a good stability at 60°C for at least 1 h. The crude cellulase exhibited a strong antibacterial activity against Staphylococcus aureus. The strain can be used in cost-efficient cellulase production for bioconversion of agricultural residual biomass into biofuels. SIGNIFICANCE AND IMPACT OF THE STUDY: The increased consumption of fossil fuels has caused serious energy crisis and environmental problem. Thus, an alternative energy source is necessary. Bioconversion of biomass, particularly agricultural residuals, into value-added bioproducts, such as biofuels and chemical solvents, has received considerable attention. In this study, the newly isolated thermophilic Bacillus subtilis strain BY-3 produces cellulase efficiently with the use of untreated corn stover as a sole carbon source. This strain possesses the thermostable cellulase that is active with diverse crop wastes with a broad pH range and is a highly promising candidate for agricultural waste management.

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

Oridonin inhibits tumor growth in glioma by inducing cell cycle arrest and apoptosis.

Glioma is the most common malignant intracranial tumors. Despite newly developed therapies, these treatments mainly target oncogenic signals, and unfortunately, fail to provide enough survival benefit in both human patients and mouse xenograft models, especially the first-generation therapies. Oridonin is purified from the Chinese herb Rabdosia rubescens and considered to exert extensive anti-cancer effects on human tumorigenesis. In this study, we systemically investigated the role of Oridonin in tumor growth and the underlying mechanisms in human glioma. We found that Oridonin inhibited cell proliferations in a dose- and time-dependent manner in both glioma U87 and U251 cells. Moreover, these anti-cancer effects were also confirmed in a mouse model bearing glioma. Furthermore, cell cycle arrest in S phase was observed in Oridonin-mediated growth inhibition by flow cytometry. Cell cycle arrest in S phase led to eventual cell apoptosis, as revealed by Hoechst 33342 staining and annexin V/PI double-staining. The cell apoptosis might be accomplished through a mitochondrial manner. In all, we were the first to our knowledge to report that Oridonin could exert anti-cancer effects on tumor growth in human glioma by inducing cell cycle arrest and eventual cell apoptosis. The identification of Oridonin as a critical mediator of glioma growth may potentiate Oridonin as a novel therapeutic strategies in glioma treatments.

Epidermal growth factor-expressing Lactococcus lactis enhances growth performance of early-weaned pigs fed diets devoid of blood plasma.

The effect of supplementing Lactococcus lactis (L. lactis) that was engineered to express epidermal growth factor (EGF-LL) to early-weaned pigs fed diets with typical levels of blood plasma (5%) or diets without blood plasma [blood plasma was substituted with soybean (Glycine max) meal and fish meal, based on amino acid supply] was examined. A total of 108 weaned piglets (19-26 d of age; mean initial BW 6.58 kg; 9 pigs per pen) were fed ad libitum according to a 2-phase feeding program without growth promoters. Three pens were assigned to each of 4 treatments: i) blood plasma-containing diet with blank bacterial growth medium (BP-Con), ii) blood plasma-containing diet with fermented EGF-LL (BP-EGF), iii) blood plasma-free diet with blank bacterial growth medium (BPF-Con), and iv) blood plasma-free diet with fermented EGF-LL (BPF-EGF). The amount of epidermal growth factor (EGF) was determined in the fermentation product and pigs were allotted 60 µg EGF/kg BW/d for 3 wk postweaning. There were no differences in overall growth performance between BP-Con and BP-EGF pigs and no differences in overall growth performance between LoCon and BPF-EGF pigs. Pigs fed BPF-EGF showed increased daily BW gain (410 vs. 260 g/d; P < 0.01) and gain:feed (0.67 vs. 0.58; P < 0.05) compared to BPF-Con pigs in wk 3 postweaning; this was comparable to values for the BP-Con group (400 g/d and 0.64). These results indicate that supplementation with EGF-LL can be effective in enhancing the performance of early-weaned piglets fed a low complexity diet and reduces the need for feeding high-quality animal proteins and antibiotics.

Digestible and metabolizable energy concentrations in copra meal, palm kernel meal, and cassava root fed to growing pigs.

An experiment was conducted to measure DE and ME in copra (Cocos nucifera) meal (CM), palm kernel meal (PKM), and cassava (Manihot esculenta) root (CR) in growing pigs. Eight boars with an initial BW of 67.3 ± 5.8 kg were individually housed in metabolism crates that were equipped with a feeder and a nipple drinker. A replicated 4 × 4 Latin square design was used with 4 dietary treatments, 4 periods, and 8 animals. A basal diet mainly contained corn (Zea mays) and soybean (Glycine max) meal. Three additional diets were formulated to contain 30% of CM, PKM, and CR. All diets contained the same proportion of corn:soybean meal ratio at 4.14:1. The apparent total tract digestibility of energy was 89.5, 84.1, 82.4, and 87.9% (P < 0.001) in the basal, CM, PKM, and CR diets, respectively. The DE in CM and PKM were greater (P < 0.05) than in CR (3440 and 3238 vs. 2966 kcal/kg as-fed). The ME in CM was greater (P < 0.05) than in CR (3340 vs. 2935 kcal/kg as-fed) but not different from the ME in PKM (3168 kcal/kg as-fed). In conclusion, CM and PKM have a higher DE value than CR, and CM has a higher ME value than CR.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

Tripterygium wilfordii hook f increase the blood concentration of tacrolimus.

OBJECTIVE: To observe the influence of the Tripterygium wilfordii Hook F (T II) on the blood concentration of tacrolimus and analyze the impact of this effect. METHOD: Twenty-two renal transplant receipts taking tacrolimus combined with the T II were selected for this study. We analyzed the blood concentrations and the rate of concentration compared with dosage (C/D rate) pre- and postcombination over 6 months. All cases underwent the CYP3A5 genotype test. RESULT: The concentrations of tacrolimus were raised to a certain degree after the combination in all the cases. The first-time elevation differed from 1 week to 4 months. The C/D rate increased by 1.7 to 7.2 times with most evaluated C/D rates ranging from 1.8 to 3.8. The elevated C/D rate of the subgroup of CYP3A5 1/1 and 1/3 (n = 10) contrasted with the 3/3 genotype subgroup (n = 12: 2.99 +/- 1.71 vs 2.55 +/- 1.07; P = .472). The mycophenolate mofetil subgroup (n = 17) was not contrasted to the mizoribine subgroup (n = 5: 2.85 +/- 1.51 vs 2.31 +/- 0.26; P = .498). CONCLUSION: T II considerably increased the blood concentration and the C/D rate of tacrolimus. The degree of increase was probably not related to the CYP3A5 genotype and the combination of immunosuppressive agents.

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China.

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.

Modulation of liver microsomal monooxygenase system by dietary n-6/n-3 ratios in rat hepatocarcinogenesis.

This study was designed to determine the effects of dietary n-3/n-6 fatty acid ratios on preneoplastic foci and the microsomal monooxygenase system in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed four kinds of diets containing 15% (wt/wt) fat with different n-6/n-3 ratios: low ratio (> or = 1.0) with tuna oil, low ratio (> or = 1.0) with perilla oil, moderate ratio (< or = 4.0), and high ratio (< or = 10.0). Hepatocarcinogenesis was induced by diethylnitrosamine and partial hepatectomy. The moderate ratio diet decreased significantly the area and number of placental glutathione S-transferase-positive foci compared with the high ratio diet and low ratio diet with perilla oil. The fatty acid composition of microsomal membrane varied extensively, reflecting the dietary n-6/n-3 ratios. Liver microsomal lipid peroxidation was significantly decreased in the group fed the low ratio diet with tuna oil compared with the moderate and high ratio groups. Glucose-6-phosphatase activity, which reflects membrane stability, was significantly higher in the low ratio groups than in the high ratio group. The monooxygenase activities were increased significantly in the moderate ratio group compared with the high ratio group. These results suggest that a moderate n-6/n-3 ratio (< or = 4.0) may be the most effective in decreasing preneoplastic foci by elevating the monooxygenase activities and n-3 fatty acids in fish oil may have a protective effect by lowering the lipid peroxidation and stabilizing the microsomal membrane during rat hepatocarcinogenesis.

New 7,20:14,20-diepoxy ent-kauranoids from Isodon xerophilus.

Three new 7,20:14,20-diepoxy-ent-kaurane diterpenoids, xerophilusins A-C (1-3), together with a known one, macrocalin B (4), were isolated from the leaves of Isodon xerophilus. Their structures were elucidated on the basis of their spectral properties and X-ray crystallographic analysis. Compounds 1, 2, and 4 showed significant cytotoxic activity against K562, HL-60, and MKN-28 cells.