[Effects of Application of Different Organic Materials on Phosphorus Accumulation and Transformation in Vegetable Fields].

Presently, the improvement of soil organic matter is the basis to ensure food security, but the accumulation and transformation characteristics of soil phosphorus (P) as affected by organic matter remain unclear. The accumulation, transformation, and migration characteristics of soil P in different soil layers of vegetable fields were researched under the application of organic materials. Six treatments were set up in the experiment:control (no fertilization), traditional fertilizer application by farmers, biochar, chicken manure, food waste, and straw application. Available phosphorus (Olsen-P), water-soluble phosphorus (CaCl2-P) content, soil phosphorus forms, soil organic matter (SOM), and pH were determined during the pepper harvest period. In the 0-5 cm and 5-10 cm soil layers, the available phosphorus content of traditional fertilization of farmers was higher, and the available phosphorus content of the four organic materials was in the order of straw > biochar > chicken manure > food waste. Compared to that with food waste, the straw and biochar treatments increased soil available phosphorus by 59.6%-67.3% and 29.1%-36.9%, respectively. The straw treatment could easily enhance the soil labile P pool, and soil labile P in the 0-5 cm soil layer increased by 47.3% and 35.1% compared with that under the chicken manure and food waste treatments, respectively. With the increase in soil depth, the proportion of available phosphorus in the chicken manure treatment decreased the least, and available phosphorus of the 20-30 cm soil layer accounted for 55.9% of the topsoil layer but only accounted for 16.0%-34.0% under treatment with the other three materials. Compared with that under the traditional fertilization of farmers, the pH significantly increased by 0.18-0.36 units after the application of organic fertilizer, and the pH of the chicken manure and food waste treatments was significantly higher than that of biochar and straw (P < 0.05). SOM content under the biochar treatment significantly increased by 7.7%-17.6% compared to that under the other three organic materials. Among the four organic materials, the straw treatment boosted the labile P pool the most, which was conducive to the rapid increase in plant-available P. Phosphorus was most likely to migrate downward under the chicken manure treatment. In the field management based on soil fertility enhancement, the application of biochar could not only improve soil pH and SOM but also avoid excessive accumulation of phosphorus in the surface layer, which decreases environmental risks.

Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet-induced obesity mice through a dual inhibition of the GIP-GIPR signaling axis.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity-promoting factor. In this study, we systematically investigated the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet-induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3-L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high-fat-diet-fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet-induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP-GIPR axis.

25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation.

BACKGROUND: The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. METHODS: A cohort of 211 participants including 151 MetS patients and 60 controls at 20-69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. RESULTS: Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders. CONCLUSIONS: 25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.

Research Advances in Pharmacology, Safety, and Clinical Applications of Yunnan Baiyao, a Traditional Chinese Medicine Formula.

Ethnopharmacology relevance: Yunnan Baiyao (YNBY), a traditional Chinese medicine formulae, has some significant properties including activating blood circulation to dissipate blood stasis (Huo-Xue-Hua-Yu), eliminating swelling and alleviating pain (Xiao-Zhong-Zhi-Tong), and eliminating necrotic tissues and promoting granulation (Qu-Fu-Sheng-Ji). Aim of this study: This paper intends to provide a comprehensive and critical analysis of studies on YNBY, proposing new possible therapeutic directions of this formula. Materials and methods: Relevant data on YNBY were retrieved from available databases and a hand-search by searching the keywords such as "Yunnan Baiyao," "pharmacology," "toxicity," and "clinical applications." Results: Traditionally, YNBY has been used to cure hemorrhage, bruises, swelling, and pain caused by injuries in the Chinese folk. Modern pharmacological studies show that YNBY possesses pharmacological activities including hemostasis, invigorating the circulation of blood, wound healing, anti-inflammation, analgesia, antibiosis, infection prevention, and other effects. Toxicological studies demonstrate that YNBY has a certain toxicology, which is mainly caused by Aconitum alkaloids from Cao-wu (CW, Aconiti Kusnezoffii Radix). The developmental non-toxic reaction dose (NOAEL) of YNBY for embryos and fetuses is 0.5 g/kg in rats. In addition, the NOAEL for fertility and early embryo development toxicity is 4.0 g/kg in rats. Clinical trials have confirmed the safety of YNBY in a large number of patients, and adverse drug reactions (ADRs) such as abdominal pain, diarrhea, allergy, and others in very few people. YNBY is routinely used in clinic to cure bleeding, pain, swelling, upper digestive tract ulcer, postoperative wound, arthritis, mouth ulcers, ulcerative colitis, etc. Conclusions: Hemostasis is a conspicuous effect of YNBY. Except for this effect, analgesia and anti-infection may be new research directions of this formula. In addition, the in vitro and in vivo pharmacology and mechanisms of action of YNBY are encouraged as well as the pharmacokinetics of this formulae. Furthermore, the material basis of the pharmacological effects of YNBY also needs clear identification.

Nontarget and high-throughput screening of pesticides and metabolites residues in tea using ultra-high-performance liquid chromatography and quadrupole-orbitrap high-resolution mass spectrometry.

A Sin-QuEChERS, coupled to UHPLC Q-Exactive Orbitrap MS, was used for nontargeted high-throughput rapid screening and quantitative analysis of residual pesticides and metabolites in green teas. The sample was extracted with 0.1% formic acid in acetonitrile with shaking, salted out and centrifuged, and purified with Sin-QuEChERS Nano solid phase extraction column; with Full MS/ddMS2 as the data collection mode, the database containing 384 pesticides combined with Trace Finder 3.0 software, In the absence of standard products, rapid screening and confirmation of potential pesticide residues in tea samples with accurate mass, isotope abundance ratio, secondary fragment ions, etc. 20 pesticides were used as quality controls to verify the screening method, and the linearity of these pesticides was between 1 and 200 µg/L, and the correlation coefficients were all greater than 0.9922. Moreover, the LOQ was between 0.002 and 0.01 mg/kg. The average recoveries of spiked tea samples were 74%-111%. Efficiency and reliability of this method were investigated by the analysis of 38 Chinese green tea samples. 18 potential residual pesticides were detected by non-targeted screening. The researchers then conducted a quantitative analysis of the 18 potential residual pesticides.

YY1-Induced lncRNA PART1 Enhanced Resistance of Ovarian Cancer Cells to Cisplatin by Regulating miR-512-3p/CHRAC1 Axis.

Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA PART1 has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of PART1 in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of PART1 and CHRAC1 were increased and miR-512-3p expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of PART1 enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that PART1 was induced by YY1 transcription factor. Moreover, it was identified that miR-512-3p was a target of PART1, and PART1 regulated the DDP resistance of OC through miR-512-3p. In addition, we screened the candidate genes of miR-512-3p., and confirmed that CHRAC1 was the downstream gene of miR-512-3p. Furthermore, the knockdown of CHRAC1 inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of miR-512-3p. Finally, we observed that PART1 regulated the expression of CHRAC1 through miR-512-3p. In conclusion, we demonstrated that YY1-induced PART1 accelerated DDP resistance of OC through miR-512-3p/CHRAC1 axis, suggesting PART1 may be a promising therapeutic target for DDP-resistant OC patients.

Recovery of hypothalamus-pituitary-gonadal dysfunction after the treatment of suprasellar germ cell tumors.

OBJECTIVE: To investigate the incidence of hypothalamus-pituitary-gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery. METHODS: A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006-2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups. RESULTS: Of the 127 suprasellar GCT patients, 75 met the follow-up criteria, 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% CI: 2.2-25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI: 1.4-17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI: 1.5-20.7, P = 0.009) were risk factors for noninitiation/recovery. CONCLUSIONS: Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.

Will the COVID-19 outbreak be a turning point for China's wildlife protection: New developments and challenges of wildlife conservation in China.

On 24 February 2020, at the brink of the global coronavirus disease 2019 (COVID-19) pandemic, the Chinese legislature adopted a decision to ban all terrestrial wildlife for food consumption. This decision set the tone for the revision of the Wildlife Protection Law (WPL), planned for release in late 2020. Both the terrestrial wildlife ban and revised WPL have the potential to greatly reduce consumption of wildlife and aid in prevention of future zoonotic disease outbreaks. The government still faces severe challenges in reducing wildlife use in traditional medicine, strengthening habitat and ecosystem conservation, committing to long-term WPL enforcement, and promoting community education and institutional reforms. However, recent progress in establishing a stricter ban on wildlife consumption, consolidating fragmented protected areas, and increased openness to public oversight are promising developments. While it is clear that global pandemics like COVID-19 can cause massive human suffering and disruption of economies; governments can no longer allow business as usual for the wildlife industry, regardless of the monetary or cultural values it brings. Here we discuss the latest development and limitations of the current wildlife legislation in China and the recommendations for improving Chinese wildlife conservation to better protect biodiversity and reduce risks of spreading zoonotic diseases to humans.

Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors.

BACKGROUND: The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. OBJECTIVE: To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. METHODS: The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. RESULTS: The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. CONCLUSION: For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the presence of healthcare resource constraints, these findings may support decision-making when considering the care of patients with metastatic GI-NETs.

The prevalence and risk factors of preterm small-for-gestational-age infants: a population-based retrospective cohort study in rural Chinese population.

BACKGROUND: Preterm birth and small for gestational age (SGA) are strong indicators of neonatal adverse outcomes. With the growing importance of preterm SGA infants, we aim to evaluate the prevalence and risk factors for preterm SGA in China. METHOD: We analyzed the data of parents and infants from a population-based cohort research of the free National Pre-pregnancy Checkups Project (NPCP) in rural China. Only singleton live births that occurred between 24 weeks +0 days and 36 weeks +6 days of pregnancy were included in this study. SGA was defined as birth weight less than the 10th percentile of the reference birth-weight-for-gestational-age population. A multiple logistic regression model was built using the statistically significant variables from the 371 variables in the questionnaire. RESULTS: A total of 11,474 singleton, preterm, live-birth infants were included. Of the total infants, 317 (2.77%) were preterm SGA infants. A higher risk of preterm SGA infants was observed among mothers who were on oral contraceptives (OR: 8.162, 95% CI: 1.622-41.072), mothers who had syphilis (OR: 12.800, 95% CI: 1.250-131.041), and mothers with a high eosinophil percentage (OR: 13.292, 95% CI: 1.282-135.796). Maternal intake of folic acid at least 3 months before pregnancy (OR: 0.284, 95% CI:0.124-0.654) and paternal intake of egg and meat (OR: 0.097,95% CI:0.030-0.315) were protective factors. Compared with North China, the incidence of preterm SGA infants was higher in South China. CONCLUSION: Preterm SGA infants were associated with both maternal and paternal factors.

Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPARγ2 Expression.

Objectives: Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor γ2 (PPARγ2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. Methods: pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPARγ2 promoter, was stably transfected into 3T3-L1 preadipocytes. PPARγ2 promoter activities were determined by assaying the luciferase activities. Then PPARγ2 promoter activities in preadipocytes and PPARγ2 mRNA levels in human subcutaneous adipocytes were measured after the administration with LLAE. Additionally, the effects of LLAE on body weight, fat mass, glucose and lipid metabolism and the expression of PPARγ2, insulin receptor substrate 1 and glucose transporter 4 (GLUT4) in visceral adipose tissue (VAT) were measured in HFD-induced obese rats treated with low or high dose [0.5 or 3.0 g crude drug/(kg.d)] LLAE for 6 weeks. Results: Ten µg/ml LLAE significantly increased the luciferase activities in 3T3-L1 cells and the stimulatory action reached 2.51 folds of controls when LLAE was 1000 µg/ml (P < 0.01). After treating 3T3-L1 cells with 100 µg/ml LLAE, the stimulatory role peaked at 32 h where it was 2.58 folds of controls (P < 0.01). Besides, 100 µg/ml LLAE significantly increased PPARγ2 mRNA levels in human adipocytes to 1.91 folds of controls (P < 0.01). In HFD-induced obese rats, administration with both low and high dose LLAE notably reduced visceral fat mass by 45.5 and 58.4%, respectively, and significantly decreased fasting serum insulin levels (P < 0.05). The high dose LLAE also significantly decreased homeostasis model assessment of insulin resistance in obese rats (P < 0.05). Furthermore, the mRNA levels of PPARγ2 and GLUT4 in VAT of obese rats were significantly increased when compared with control rats, and were notably suppressed by LLAE intervention for 6 weeks (P < 0.05). Conclusion: LLAE significantly reduces visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats. These beneficial effects of LLAE may associate with its role in stimulating PPARγ2 expression in preadipocytes and subcutaneous adipocytes and suppressing PPARγ2 and GLUT4 expression in VAT.

Occurrence and incidence of 18 per- and polyfluoroalkyl compounds in edible oils commonly consumed in Guiyang, China.

A systematic examination was conducted for the first time of a wide carbon-chain range of per- and polyfluoroalkyl compounds (PFASs) in 83 samples of edible vegetable and animal oils from Guiyang, China. The occurrence and levels of 18 PFASs in seven types of edible oil were analysed. Analytes were determined based on a simplified, sensitive and reliable solvent extraction and liquid chromatography-tandem mass spectrometry method. Ten target PFASs were found and the most frequently detected compounds with maximum concentration were PFOS (88%, 1.93 ng g-1), PFNA (55.4%; 6.76 ng g-1), PFHxS (39.8%; 0.36 ng g-1), and PFOA (16.9%; 0.15 ng g-1), respectively. The total PFASs concentrations ranged from 0.02 to 6.76 ng g-1, with a mean of 0.94 ng g-1. Significant differences of occurrence between vegetable oils and animal oils were demonstrated based on comparative analysis of the existing data. The investigation results showed that the effect of production reductions of PFOS and PFOA by regulatory was also reflected in edible oils. The dietary intakes of PFOS and PFOA for adults were estimated, which were lower than the available tolerable daily intake (TDI). Because of the global lack of food regulatory thresholds for most per- or polyfluoroalkyl compounds, it was difficult to draw any conclusion at this stage as to how human health is affected through exposure to these compounds. The baseline information of this study will assist in guiding the direction for future investigations and monitoring studies on occurrence, fate and human health-effect research of PFASs.

A Risk Score for Fluconazole Failure among Patients with Candidemia.

This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive Candida culture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics, Candida species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow test P value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.

Cold/hot pad differentiating assay of property differences of Mahuang and Maxingshigan decoctions.

CONTEXT: Chinese medicines with different cold/hot properties have various pharmacological actions on multiple organisms. OBJECTIVE: The objective of this study was to explore the cold/hot property differences of traditional Chinese medicine formulas of Mahuang and Maxingshigan decoctions. MATERIALS AND METHODS: A novel cold/hot pad differentiating assay method based on the Intelligent Animal Temperature Tropism Behavior monitoring system at 20 °C (cold pad) and 30 °C (hot pad) was introduced to investigate the variability of temperature tropism among the mice treated by 0.4 mL/20 g (drug volume/body weight) of Mahuang decoction and Maxingshigan decoction, respectively. Meanwhile, the oxygen consumption and activities of adenosine triphosphatase (ATPase) were measured to explore the energy metabolism mechanism. RESULTS: Results showed that the differences between cold/hot properties of Mahuang decoction and Maxingshigan decoction were significant (p < 0.05). Mahuang decoction produced significant synergic effect (a combination index of 1.60), while Maxingshigan decoction expressed significant antagonistic effect (a combination index of 0.35). The changes of energy metabolism including ATPase activity and oxygen consumption might be the possible factors to result in the differences. Those influences tended to be coherent with the definition of cold/hot properties of Chinese medicines based on traditional Chinese medicinal theory. CONCLUSIONS: The results indicated that the method based on cold/hot pad differentiating array could objectively and quantitatively represent the cold/hot properties of different compatibilities of traditional Chinese medicines in an ethological way according to the changes of animal's temperature tropism. These findings would provide some experimental basis and data references as well as a novel evaluation method for the study of the regularity of recipe composition.

Biothermodynamic Assay of Coptis-Evodia Herb Couples.

Objective. To illustrate the difference in cold/hot natural properties and therapeutic effect of coptis-evodia herb couples by using cold/hot plate differentiating technology and microcalorimetry combined with material basis analysis in vivo and in vitro. It showed that animal retention ratio in hot pad significantly decreased along with the decrease in coptis proportion in coptis-evodia herb couples. In addition, Zuojin wan markedly reduced the retention ratio of gastritis mice in the hot pad, while Fanzuojin wan displayed an opposite result. Further, Mg(2+)-ATPase, Ca(2+)-ATPase, and T-AOC activity significantly weakened in coptis-treated group in the livers of the mice. In the gastric cells from the gastritis mice, Fanzuojin wan remarkably increased calorific value for growth and metabolism, while Zuojin wan significantly reduced the calorigenic effect. It suggested that the changes in the major chemical compositions (especially alkaloids) were the material base-induced transformation between "cold" and "hot" syndromes. The material basis which affected the transformation between "cold" and "hot" syndromes might be X2, X3, X4, X8, epiberberine hydrochloride, jatrorrhizine hydrochloride, coptisine sulphate, palmatine hydrochloride, and berberine hydrochloride. The CHPD combined with microcalorimetry technology is a good method to determine the differences in the "cold" and "hot" natural properties of coptis-evodia herb couples.

Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.

Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and, although it is considered essential, deficiency has not been linked to disease. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the major facilitator superfamily domain-containing 2a (MFSD2A) protein. MFSD2A transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues. Affected individuals exhibited a lethal microcephaly syndrome linked to inadequate uptake of LPC lipids. The MFSD2A mutations impaired transport activity in a cell-based assay. Moreover, when expressed in mfsd2aa-morphant zebrafish, mutants failed to rescue microcephaly, BBB breakdown and lethality. Our results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport of DHA in humans.

Hormone-sensitive lipase is involved in the action of hydroxysafflor yellow A (HYSA) inhibiting adipogenesis of 3T3-L1cells.

BACKGROUND: Safflor yellow A (SY) has been demonstrated to be beneficial to cardiovascular system. Our previous study showed that hydroxysafflor yellow A (HSYA), a main component of SY, could increase peroxisome proliferator-activated receptor γ mRNA expression. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. METHODS: The proliferation and adipogenesis of 3T3-L1 cells treated with HSYA was studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining and intracellular triglyceride assay methods. HSL mRNA expression and promoter activity were studied by real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. RESULTS: HSYA (0.1 mg/L) significantly inhibited the proliferation of 3T3-L1 cells when compared with control cells in 8 h. This effect was further enhanced with the extension time (24 to 96 h) and an increase of concentration of HSYA (1-10 mg/L). The maximal inhibitory action was observed at 0.1 mg/L HSYA in 72 h (86±11.8% vs. 100±4.1%, p<0.01). HSYA notably reduced the amount of intracellular lipid and triglyceride content in adipocytes to 85% (1 mg/L) and 75% (100 mg/L) on Day 4 following the differentiation, respectively, while increased HSL mRNA expression and promoter activities to 2.7 fold and 1.55 fold, respectively (p<0.01), in differentiated 3T3-L1 adipocytes. CONCLUSIONS: HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.

Comparative outcomes of everolimus, temsirolimus and sorafenib as second targeted therapies for metastatic renal cell carcinoma: a US medical record review.

OBJECTIVE: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus, temsirolimus, and sorafenib following initial treatment with a tyrosine kinase inhibitor (TKI) in community and academic practices throughout the US. RESEARCH DESIGN AND METHODS: Medical records of mRCC patients who received everolimus, temsirolimus or sorafenib as their second therapy following a TKI were retrospectively reviewed from a nationally representative panel of oncologists. Overall survival (OS) and progression-free survival (PFS) of second targeted therapies were compared using multivariable Cox proportional hazard models, with adjustment for demographics, disease severity and prior treatments. RESULTS: A total of 233, 178, and 123 mRCC patients receiving everolimus, temsirolimus, and sorafenib, respectively, as second targeted therapies were included. Eighty-six percent used sunitinib and the remainder used sorafenib or pazopanib as their initial TKI. After adjusting for baseline characteristics, everolimus was associated with significantly prolonged OS (hazard ratio [HR] 0.60; CI 0.42-0.85; p = 0.004) and PFS (HR 0.73; CI 0.54-0.97; p = 0.032) compared to temsirolimus. Everolimus was associated with significantly longer OS (HR 0.66; CI 0.44-0.99; p = 0.045) and numerically longer PFS compared to sorafenib. No significant differences were observed between temsirolimus and sorafenib. LIMITATIONS: Despite adjustment for multiple patient characteristics, comparisons between treatment groups may be confounded by unobserved factors in this retrospective observational study. Tolerability outcomes were not collected. CONCLUSIONS: In this retrospective, non-randomized study of mRCC patients with prior TKI treatment, everolimus was associated with significantly prolonged OS and PFS compared to temsirolimus and significantly prolonged OS compared to sorafenib.

Treatment patterns, resource use, and economic outcomes associated with atypical antipsychotic prescriptions in children and adolescents with attention-deficit hyperactivity disorder in quebec.

OBJECTIVE: To assess treatment patterns, health care resource utilization (HRU), and costs among previously stimulant-treated children and adolescents with attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic (AAP) prescriptions in Quebec. METHODS: Health care claims data extracted from Quebec's provincial health plan database between March 2007 and February 2012 were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking a stimulant and either switched to, or augmented with, an AAP (with the first AAP defined as the index AAP) without a documented diagnosis for which AAPs are Health Canada-approved were included. Discontinuation, augmentation, and switching of the index AAP during the 12-month, follow-up period were estimated using Kaplan-Meier survival analysis. HRU and costs for the 6 months before (baseline period) and after initiation of the index AAP were compared. RESULTS: A total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6 to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation, augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively. Patients had, on average, more all-cause prescription fills (22.2, compared with 13.3) and incurred more all-cause pharmacy ($889, compared with $710), total medical ($1096, compared with $644), and total health care ($1985, compared with $1354) costs during the 6-month study period than during the 6-month baseline period (all P < 0.05). Similarly, ADHD-related total health care costs were higher during the study period ($1269, compared with $835; P < 0.05); all-cause and ADHD-related total health care costs increased by 46.6% and 52.0%, respectively. CONCLUSION: Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs.

Influence of nonpolar substances on the extraction efficiency of six alkaloids in Zoagumhwan investigated by ultra performance liquid chromatography and photodiode array detection.

A reverse phase ultra performance liquid chromatography and photodiode array (UPLC-PDA) detection method was established for the determination of six alkaloids in Zoagumhwan (ZGW), and further for investigating the influence of nonpolar substances on the extraction efficiency of these alkaloids. The method was based on a BEH C(18) (50 mm × 2.1 mm, 1.7 µm) column and mobile phase of aqueous phosphoric acid and acetonitrile including 0.05% buffer solution under gradient elution. ZGW samples of ZGW I, II, III and IV were obtained and prepared by pre-processing the crude materials of Coptidis rhizoma and Evodiae fructus using four technologies, namely direct water decoction, removal of nonpolar substances in Evodiae fructus by supercritical fluid extraction (SFE), removal of nonpolar substances in ZGW by SFE and removal of nonpolar substances in ZGW by steam distillation. The developed and validated UPLC-PDA method was precise, accurate and sensitive enough based on the facts that the six alkaloids showed good regression (r > 0.9998), the limit of detections and quantifications for six alkaloids were less than 28.8 and 94.5 ng/mL, respectively, and the recovery was in the range of 98.56%-103.24%. The sequence of the total contents of six alkaloids in these samples was ZGW II > ZGW IV > ZGW III > ZGW I. ZGW II, in which nonpolar substances, including essential oils, were firstly removed from Evodiae fructus by SFE, had the highest content of the total alkaloids, indicating that extraction efficiency of the total alkaloids could be remarkably increased after Evodiae fructus being extracted by SFE.