[Differences in uptake, utilization and loss of nitrogen and phosphorus in a Chinese double rice cropping system under different irrigation and fertilization managements]. / 不同水肥耦合下双季稻氮磷吸收、利用与流失差异.

In order to optimize water and fertilizer use in the double-cropping rice in eastern Fujian Province, a field runoff plot experiment was conducted to investigate rice yield, nutrient uptake, and runoff losses of N (nitrogen) and P (phosphorus) in the T0(no chemical fertilization with traditional flooding irrigation), T1(common chemical fertilizer of 273 kg N·hm-2, 59 kg P·hm-2, and 112 kg K·hm-2 combined with traditional flooding irrigation), T2(chemical fertilizer of 240 kg N·hm-2, 52 kg P·hm-2, and 198 kg K·hm-2 combined with traditional flooding irrigation) and T3(chemical fertilizer combined with shallow intermittent irrigation) treatments. Results showed that early rice grain yield in the T1, T2 and T3 treatments significantly increased by 0.7, 1.0, 1.1 times, late rice grain yield significantly increased by 0.9, 1.1, 1.0 times compared to that in the T0 treatment, respectively. The T1, T2 and T3 treatments significantly increased the uptake of N and P in aboveground parts of the plants, especially in grains. The T1, T2 and T3 treatments significantly increased N uptake by 1.1, 1.2, 1.2 times, increased P uptake by 0.9, 1.4, 1.6 times in early-season grains, and significantly increased N uptake by 0.8, 1.0, 1.0 times, increased P uptake by 0.7, 0.9, 0.9 times in late-season grains, compared to T0, respectively. Furthermore, T3 increased agronomic N use efficiency (AEN) and agronomic P use efficiency (AEP) by 71.1% and 69.2% in early rice plants, increased AEN and AEP by 26.4% and 25.0% in late rice plants, whereas T3 decreased total dissolved N (DN) by 16.0% in comparison with T1. Dissolved inorganic N loss in surface runoff occurred mainly in the form of NO3--N (nitrate N) under different water and fertilizer regimes. However, there were no significant differences in AEN and AEP between T2 and T3 treatments. These findings suggested that optimal applications of water and fertilizers (T3) might increase N and P uptake in rice plants, maintain yield, and reduce N loss, especially in the form of NO3--N in surface water from early rice field. In general, this study could provide theoretical support for the optimization of irrigation and fertilization and for the control of N and P non-point source pollution from the double cropping rice paddy fields in eastern Fujian Province.

Idebenone-Activating Autophagic Degradation of α-Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson's Disease: A Network Pharmacological Approach.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD. METHOD: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant α-synuclein was used to validate the molecular mechanism. RESULT: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted α-synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear α-synuclein. CONCLUSION: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of α-synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.

Evaluation on Effectiveness and Safety of Chinese Herbs in Treatment of Sub-health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbs in the treatment of sub-health systematically. METHODS: Nine databases were systematically and extensively searched to collect randomized controlled trials (RCTs) about Chinese herbs in the treatment of sub-health. The outcomes included overall effective rate, main symptoms, quality of life, etc. Literature screening, data extraction and quality assessment were conducted according to Cochrane Handbook 5.1. Meta-analysis was conducted to the included literature with Review Manager Software. RESULTS: Seventy-two studies involving 9,296 patients with sub-health were included with 4,908 patients in experimental groups and 4,387 patients in control groups. The overall quality of included clinical research was not high. In the aspect of improving overall effective rate, relieving main symptoms, Pittsburgh sleep quality index (PSQI) score, Athens Insomnia Scale (AIS) score, Fatigue Scale-14 (FS-14), Cornell Medical Index (CMI) score and discontinuation rate, the effects of experimental groups were better than that of control groups. According to available research reports, adverse reactions in Chinese herb groups were mainly mild gastrointestinal symptoms, which did not affect the treatment. CONCLUSION: Chinese herbs have a curative effect in the treatment of sub-health. However, there are no clear criteria for diagnosis and curative effectiveness judgment globally, which would affect the accuracy of curative effect evaluation.

Hyperin Enhances the Sensitivity of HCT8/VCR Colon Cancer Cell Line to Vincristine by Down-Regulating P-Glycoprotein.

BACKGROUND: Long-term chemotherapy reduces the sensitivity of colon cancer cells to chemotherapeutics like vincristine (VCR) and lead to drug resistance, which has become a major barrier for colon cancer treatment. Calcium antagonists are used as clinical tumor multidrug resistance reversal agents to regulate the P-glycoprotein (P-gp) level and block efflux pump function now, but they have significant side effects. Hyperin as active component with low toxicity in traditional Chinese medicine has calcium antagonistic effect. Thus, the purpose of this study was to evaluate the inhibitory effect of hyperin on the growth of HCT8/VCR colon cancer cell line (vincristine-resistant) and analyze the enhancing effect of hyperin on the sensitivity of cancer cells to VCR and its relationship to the expression and function of P-gp. METHODS: Using the MTT method, we investigated the influence of hyperin, VCR alone, and hyperin plus VCR on the growth of HCT8/VCR cells. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the fluorescence intensity of intracellular Rho123. RESULTS: The inhibitory effect of hyperin at the dose of 12.5 µM on HCT8/VCR cell growth was not enhanced as time progressed and no significant inhibitory effect was found for VCR-treated cells at the dose of 2 µM. But the inhibition of cell growth was observed after the combined treatment of hyperin (12.5 µM) and VCR (2 µM). P-gp expression levels in HCT8/VCR cells treated with hyperin plus VCR were markedly lower than the levels in control cells and those treated with VCR. In addition, the intensity of Rho123 fluorescence of HCT8/VCR cells treated with hyperin plus VCR or hyperin alone was significantly higher than intensity observed in control cells and those treated with VCR alone. CONCLUSIONS: Hyperin synergistically augments the growth inhibitory effect of vincristine. The underlying mechanism most probably involves down-regulation of P-gp expression and inhibiting the function of the P-gp pump in HCT8/VCR cells.

[Effect of combination of gastrodia and uncaria on pharmacokinetics of gastrodin and rhynchophylline].

To investigate the effect of the combination of gastrodia and uncaria on the pharmacokinetics of gastrodin and rhynchophylline, and determine their pharmacokinetic parameters after administration of the combination of gastrodia and uncaria at the ratio of 12∶9. Compared with uncaria group or gastrodia group, Cmax and AUC of both gastrodin and rhynchophylline were significantly increased, and tmax was retroceded by 1.5 h for rhynchophylline and 0.25 h for gastrodin. The change of tmax resulted in a 1.25 h difference in the peak time between gastrodin and rhynchophylline , which was the same between them. Uncaria shows a more effect in suppressing hyperactive Yang, while gastrodia has a balancing effect by nourishing Yin and suppressing hyperactive Yang. As a result, gastrodia could exert the effect in nourishing Yin and suppressing effect of uncaria, which could avoid the deficiency of Yang affecting Yin due to mono-treatment of uncaria. On one hand, the enhanced AUC and Cmax of gastrodin could increase the average plasma drug concentration of gastrodin, and remedy the losing effect of uncaria at the early stage; On the other hand, the increased AUC and Cmax of rhynchophylline could make up the quick elimination of gastrodia in vivo at the late stage. Their combination could lead to an increased anti-hypertensive effect with the balance of Yin and Yang. They showed unique advantages compared with simple dosage increase of western medicines. The results were consistent with the principle of TCM treatment for the hypertension due to hyperactivity of the liver Yang. In short, this study gives a good pharmacokinetic explanation of the balance of Yin and Yang and TCM treatment for both symptoms and root cause.

Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.

Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles such as blindness, randomization and control in RCTs, while requiring reporting in accordance with international standards.

Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia.

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1 ß in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted.

Metabonomics-based study of clinical urine samples in suboptimal health with different syndromes.

Objective. To explore the urinary biochemistry features of syndromes of traditional Chinese medicine (TCM) such as syndrome of stagnation of liver Qi, spleen deficiency, liver Qi stagnation, and spleen deficiency (LSSDS) in sub-optimal health status (SHS). Methods. 12 cases for each syndrome group in SHS were selected, 12 subjects were used as a normal control group, and (1)H NMR detection was, respectively, carried out, and the data was corrected by the orthogonal signal correction (OSC) and then adopted a partial least squares (PLS) method for discriminate analysis. Results. The OSC-PLS (ctr) analysis results of the nuclear overhauser enhancement spectroscopy (NOESY) detection indicated that the syndromes in SHS could be differentiated, and there were significant differences in the levels of metabolites of the urine samples of the four groups; the biomarkers of LSSDS in SHS were found out. The contents of citric acid (2.54 and 2.66), trimethylamineoxide (3.26), and hippuric acid (3.98, 7.54, 7.58, 7.62, 7.66, 7.82, and 7.86) in the urine samples of LSSDS group were lower than that of the normal control group. Conclusion. There are differences in the (1)H-NMR metabolic spectrum of the urine samples of the four groups, and the specific metabolic products of the LSSDS in SHS can be identified from metabonomics analysis.

Development and evaluation of a traditional Chinese medicine syndrome questionnaire for measuring sub-optimal health status in China.

OBJECTIVE: Sub-optimal health status (SHS), in which a person's mind and body exists in a low-quality state of being between disease and health, has become a public health problem that cannot be ignored in China. SHS measurement presents a challenge to the academic fields. We developed and evaluated a questionnaire from the perspective of traditional Chinese medicine (TCM) that embodies the features of TCM syndrome diagnosis for measuring SHS in China. METHODS: The construction of the theoretical framework of the questionnaire was based on a literature review, an expert questionnaire survey and group interviews. The subscales and questionnaire items were screened through a pilot study using statistical means and qualitative analysis. Reliability tests that were used included test-retest reliability, Cronbach's a coefficient, split-half reliability; validity tests included content validity, criterion validity, discrimination validity and construct validity. RESULTS: The final questionnaire, the SHSQ-50, included 50 five-class quantifiable items that encompassed nine subscales: liver stagnation syndrome, liver-Qi deficiency syndrome, spleen-Qi deficiency syndrome, liver-fire syndrome, heart-fire syndrome, stomach-fire syndrome, heart-Qi deficiency syndrome, lung-Qi deficiency syndrome and dampness syndrome. Questionnaires were completed by 268 of the 288 SHS subjects (93.0%) and by 86 of the 94 healthy subjects (91.5%). The Cronbach a coefficients, split-half coefficients and stability coefficients ranged from 0.70 to 0.95, 0.67 to 0.87 and 0.88 to 0.98, respectively, for the overall scores and subscales. The Wilcoxon rank test showed statistically significant differences in the subscales and overall scores between the SHS group and the healthy group (P < 0.01). Twelve factors with an eigenvalue greater than one were extracted by factor analysis and merged into nine factors, for which the cumulative contribution rate was 63.63%. The nine factors were corresponded to the overall structure of the questionnaire. CONCLUSION: The SHSQ-50 is a reliable and valid instrument for measuring TCM syndrome diagnosis of SHS in China.

Diagnosis Analysis of 4 TCM Patterns in Suboptimal Health Status: A Structural Equation Modelling Approach.

Background. We illustrated an example of structure equation modelling (SEM) in the research on SHS to explore the diagnosis of the Sub optimal health status (SHS) and provide evidence for the standardization of traditional Chinese medicine (TCM) patterns in SHS. And the diagnosis of 4 TCM patterns in SHS was evaluated in this analysis. Methods. This study assessed data on 2807 adults (aged 18 to 49) with SHS from 6 clinical centres. SEM was used to analyze the patterns of SHS in TCM. Parameters in the introduced model were estimated by the maximum likelihood method. Results. The discussed model fits the SHS data well with CFI = 0.851 and RMSEA = 0.075. The direct effect of Qi deficiency pattern on dampness pattern had the highest magnitude (value of estimate is 0.822). With regard to the construct of "Qi deficiency pattern", "fire pattern", "stagnation pattern" and "dampness pattern", the indicators with the highest load were myasthenia of limbs, vexation, deprementia, and dizziness, respectively. It had been shown that estimate factor should indicate the important degree of different symptoms in pattern. Conclusions. The weights of symptoms in the respective pattern can be statistical significant and theoretical meaningful for the 4 TCM patterns identification in SHS research. The study contributed to a theoretical framework, which has implications for the diagnosis points of SHS.