Circadian rhythms of risk factors and management in atherosclerotic and hypertensive vascular disease: Modern chronobiological perspectives of an ancient disease.

Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused by vascular endothelial dysfunction, cholesterol deposition, smooth muscle proliferation, inflammatory cell infiltration and connective tissue accumulation. Hypertension is an independent and controllable risk factor for atherosclerotic cardiovascular disease (CVD). Conversely, atherosclerosis hardens the arterial wall and raises arterial blood pressure. Many CVD patients experience both atherosclerosis and hypertension and are prescribed medications to concurrently mitigate the two disease conditions. A substantial number of publications document that many pathophysiological changes caused by atherosclerosis and hypertension occur in a manner dependent upon circadian clocks or clock gene products. This article reviews progress in the research of circadian regulation of vascular cell function, inflammation, hemostasis and atherothrombosis. In particular, it delineates the relationship of circadian organization with signal transduction and activation of the renin-angiotensin-aldosterone system as well as disturbance of the sleep/wake circadian rhythm, as exemplified by shift work, metabolic syndromes and obstructive sleep apnea (OSA), as promoters and mechanisms of atherogenesis and risk for non-fatal and fatal CVD outcomes. This article additionally updates advances in the clinical management of key biological processes of atherosclerosis to optimally achieve suppression of atherogenesis through chronotherapeutic control of atherogenic/hypertensive pathological sequelae.

Examining industrial air pollution embodied in trade: implications of a hypothetical China-UK FTA.

Very few developed economies have a full free trade agreement (FTA) with China. This study employs one GTAP model and builds an extended environmental multi-region input-output model to investigate a hypothetical China-UK FTA, concerning embodied industrial emissions of SO2, PM2.5, NOX, and NH3. The economic sectors are also classified based on their embodied pollution intensity and trade advantage index under various FTA scenarios. Results show that the UK's GDP and welfare and China's welfare will increase, along with changes in their trade structures. Overall, this FTA brings about larger net impacts on embodied emissions of SO2 than on PM2.5, NOX and NH3, and both countries are net importers of the latter three pollutants. Key sectors such as non-metallic mineral products, chemical products, and agriculture are inclined to become less competitive and less polluting under the FTA. The inclusion of agri-food sectors exhibits slight counteracting effects in general. The findings are of policy importance as they provide insights into how best to target key sectors, seeking a balance between trade development and environmental protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02612-z.

Transcriptional regulation of vascular smooth muscle cell proliferation, differentiation and senescence: Novel targets for therapy.

Vascular smooth muscle cells (SMC) possess a unique cytoplasticity, regulated by transcriptional, translational and phenotypic transformation in response to a diverse range of extrinsic and intrinsic pathogenic factors. The mature, differentiated SMC phenotype is physiologically typified transcriptionally by expression of genes encoding "contractile" proteins, such as SMα-actin (ACTA2), SM-MHC (myosin-11) and SM22α (transgelin). When exposed to various pathological conditions (e.g., pro-atherogenic risk factors, hypertension), SMC undergo phenotypic modulation, a bioprocess enabling SMC to de-differentiate in immature stages or trans-differentiate into other cell phenotypes. As recent studies suggest, the process of SMC phenotypic transformation involves five distinct states characterized by different patterns of cell growth, differentiation, migration, matrix protein expression and declined contractility. These changes are mediated via the action of several transcriptional regulators, including myocardin and serum response factor. Conversely, other factors, including Kruppel-like factor 4 and nuclear factor-κB, can inhibit SMC differentiation and growth arrest, while factors such as yin yang-1, can promote SMC differentiation whilst inhibiting proliferation. This article reviews recent advances in our understanding of regulatory mechanisms governing SMC phenotypic modulation. We propose the concept that transcription factors mediating this switching are important biomarkers and potential pharmacological targets for therapeutic intervention in cardiovascular disease.

Environmental damage cost assessment from municipal solid waste treatment based on LIME3 model.

Environmental damage cost can measure the impact of pollution caused by human activity on final safeguard subjects from endpoint perspective. Application of environmental damage cost to municipal solid waste (MSW) management is still rare. To fill such a research gap, this study established a MSW environmental damage cost assessment method using Life Cycle Impact Assessment Method based on Endpoint (LIME) model. Four types of environmental damage cost, namely, primary productivity, social assets, biodiversity and human health for waste treatment were investigated in the city of Shanghai. Results show that the environmental damage cost was 113.7, 116.9, 140.0, 144.0 and 170.8 million dollars in Shanghai from 2014 to 2018, respectively. Damage cost of social assets was the dominant component, accounting for about 55%. Landfill mainly caused social assets damage cost, while incineration mainly caused human health damage cost. Scenarios analysis further revealed that after implementing MSW separation, the total environmental damage cost could be reduced by about 1/3. The best MSW treatment method is fermentation, followed by compost, incineration and landfill, with unit environmental damage cost being 0.22, 4.51, 16.04 and 23.47 USD/ton, respectively.

Life cycle thinking-based eco-compensation for gold ingot production: a case study in China.

Unearthing mineral resources has brought about serious impacts on the natural ecosystem. Eco-compensation of mineral resources has been proposed; however, the lack of a systematic method for evaluating eco-compensation criteria has limited its implementation and progress. Life cycle thinking is proposed for evaluating eco-compensation criteria because it provides a holistic view for stakeholders through all the stages of production. In this study, the economic loss caused by resource exhaustion and environmental externalities is both studied to evaluate the eco-compensation criteria by integrating life cycle assessment, emergy accounting, and equivalent factor of ecosystem services. Gold production is used as an application for the explanation of this integrated framework. Results show that the life cycle eco-compensation of gold ingot per gram is 4.87 $, including both the economic loss of the gold itself (2.00 $) and the loss in terms of environmental externalities damage (2.87 $). Environmental costs include damage to ecosystem services because of land occupation (75.68%), damage to human health (12.28%), and the costs associated with climate change (12.04%). The results of this study can enrich the theory and future researches of eco-compensation criteria. Finally, suggestions and helpful insights are provided for policy-makers to enhance decision-making regarding eco-compensation criteria.

Guidelines for the design and conduct of human clinical trials on ingestion-time differences - chronopharmacology and chronotherapy - of hypertension medications.

Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e. biological rhythm-dependent effects on the kinetics and dynamics of medications, and chronotherapy, i.e. the timing of pharmaceutical and other treatments to optimize efficacy and safety) trials should be to explore the potential impact of endogenous circadian rhythms on the effects of medications. Such investigations and outcome trials mandate adherence to the basic standards of human chronobiology research. In-depth review of the more than 150 human hypertension pharmacology and therapeutic trials published since 1974 that address the differential impact of upon-waking/morning versus at-bedtime/evening schedule of treatment reveals diverse protocols of sometimes suboptimal or defective design and conduct. Many have been "time-of-day," i.e. morning versus evening, rather than circadian-time-based, and some relied on wake-time office BP rather than around-the-clock ambulatory BP measurements (ABPM). Additionally, most past studies have been of too small sample size and thus statistically underpowered. As of yet, there has been no consensual agreement on the proper design, methods and conduct of such trials. This Position Statement recommends ingestion-time hypertension trials to follow minimum guidelines: (i) Recruitment of participants should be restricted to hypertensive individuals diagnosed according to ABPM diagnostic thresholds and of a comparable activity/sleep routine. (ii) Tested treatment-times should be selected according to internal biological time, expressed by the awakening and bed times of the sleep/wake cycle. (iii) ABPM should be the primary or sole method of BP assessment. (iv) The minimum-required features for analysis of the ABPM-determined 24 h BP pattern ought to be the asleep (not "nighttime") BP mean and sleep-time relative BP decline, calculated in reference to the activity/rest cycle per individual. (v) ABPM-obtained BP means should be derived by the so-called adjusted calculation procedure, not by inaccurate arithmetic averages. (vi) ABPM should be performed with validated and calibrated devices at least hourly throughout two or more consecutive 24 h periods (48 h in total) to achieve the highest reproducibility of mean wake-time, sleep-time and 48 h BP values plus the reliable classification of dipping status. (vii) Calculation of minimum required sample size in adherence with proper statistical methods must be provided. (viii) Hypertension chronopharmacology and chronotherapy trials should preferably be randomized double-blind, randomized open-label with blinded-endpoint, or crossover in design, the latter with sufficient washout period between tested treatment-time regimens.

Chronotherapy of cardiac and vascular disease: timing medications to circadian rhythms to optimize treatment effects and outcomes.

Circadian rhythms impact cardiac and vascular pathophysiology, resulting in 24-hour patterning of symptoms and life-threatening/ending events (chronopathology), plus kinetics and dynamics of medications (chronopharmacology), resulting in administration-time differences in efficacy and safety. Scheduling medications according to circadian rhythm determinants (chronotherapy) can improve treatment effects, for example, before dinner/bedtime ingestion of cholesterol-lowering medications and acetylsalicylic acid, respectively, exerts enhanced control of hypercholesterolemia and after-awakening peak of platelet aggregation; bedtime ingestion of conventional hypertension medications optimizes normalization of sleep-time blood pressure (BP)-strongest independent BP marker of cardiovascular disease (CVD) risk-and most effectively prevents (chronoprevention) CVD morbidity and mortality. Exploration of chronotherapeutic strategies to improve management of cardiac arrhythmias and vascular pathophysiology is still awaited.

Differences and Correlations of Morphological Characteristics and Fatty Acid Profiles of Seeds of Toona sinensis.

Toona sinensis (A.Juss.) M.Roem., a multi-purpose tree of Meliaceae, is widely distributed and intensively cultivated in Asia, yet its high yielding, lipid-rich seeds are rarely exploited. The present study systematically analyzed the differences and correlations of seed morphological characteristics and fatty acid (FA) profiles of 62 representative T. sinensis germplasms distributed across northern to southern China. T. sinensis seeds were rich in total FAs (TFA, 107.03-176.18 mg/g). Additionally, linoleic acid (54.69-100.59 mg/g), α-linolenic acid (ALA, 22.47-45.02 mg/g), oleic acid (OA, 5.12-23.94 mg/g), palmitic acid (6.87-14.14 mg/g), stearic acid (SA, 3.13-6.57 mg/g) and elaidic acid (1.70-2.88 mg/g) were the major FAs measured by GC/MS analysis. Size (average width of 3.94±0.01 mm and length of 5.79±0.02 mm) and mass (average thousand-seed weight of 10.52±0.17 g) were greater in T. sinensis seeds collected south than north of 30° latitude. These traits were also positively correlated with unsaturated FA content and negatively related to SA and saturated FA contents (P<0.05). Significant positive correlations were found between seed length and polyunsaturated FA (R2 =0.370) and ALA levels (R2 =0.296), as well as between thousand-seed weight and monounsaturated FAs (R2 =0.309) and OA levels (R2 =0.297) (P<0.05). Seventeen T. sinensis germplasms gathered by cluster analysis as cluster IV were determined as desirable for oil processing due to their higher TFA and ALA contents and greater seed size and mass than others. Generally, the wider, heavier, and especially longer seeds of T. sinensis contain much higher levels of FAs, especially ALA, and are the more promising sources for breeding and the oil processing industry.

Structure of human GABAB receptor in an inactive state.

The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.

A bibliometric analysis of ecosystem services evaluation from 1997 to 2016.

Ecosystems play critically important roles in supporting human society, while human activities seriously disturb their initial balance. Lots of researches on ecosystem services are conducted due to the increasing concern on ecological security worldwide. In order to provide valuable insights for understanding the primary performance of ecosystem services-related studies, a qualitative and quantitative analysis by using a bibliometric tool is performed in this study. Journal impact factor, CiteScore, and h-index are used for identifying influential journals, while h-index is used for recognizing productive countries/territories and institutions. Social network analysis of countries/territories and institutions is visualized, respectively, so that relationships among them can be uncovered. Citation analysis of publications and co-occurrence analysis of high-frequency keywords are also performed to explore hotspots and popular methods in this field. This study uncovers a holistic picture on the primary performance of ecosystem services-related literatures published from 1997 to 2016, including journals, countries/territories, and institutions. Results find that forest, agriculture, and wetland ecosystems attract lots of attention. Finally, major methods used for ecosystem services evaluation are identified and discussed. Research outcomes will provide valuable insights to stakeholders interested in ecosystem services.

A bibliometric analysis on waste electrical and electronic equipment research.

Waste electrical and electronic equipment (WEEE) contains both toxic and valuable materials. Due to rapid development of information and communication technologies (ICT), a large amount of WEEE have been produced, leading to increasing academic efforts in this field. This study aims to depict the trends and features of WEEE-related studies through a bibliometric analysis. The results show that the total number of WEEE-related publications had sharply increased, with China as the leading country. University of Chinese Academy of Sciences is the most productive WEEE-related research institution, while Mai BX is the most productive author. As such, Waste Management, Journal of Cleaner Production, and Environmental Science & Technology are the most influential journals. The research hotspots of WEEE mainly focus on the recycling and treatment technologies, environmental impacts, and relevant policies of WEEE. By tracing the evolutionary pathway of WEEE research, it is clear that the research frontiers have switched from electronic equipment, extended producer responsibility, sediment, environment and design, risk assessment to life cycle assessment, mobile phone, and behaviors. This study provides valuable insights to those WEEE-related scholars so that they can identify their own research topics and partners. This paper is one of the first studies in WEEE research field that offers critical discussions and suggestions related to research development and future trends, and used visualized tools to present the holistic picture of this field.

Impact assessment of energy utilization in agriculture for India and Pakistan.

Sustainable food production is a key concern across countries in South Asia. Most assessments of sustainable agriculture in this region focus on the availability and affordability of resource inputs. However, studies accounting for environmental footprint of agricultural activities in South Asian countries are limited in the existing literature. This paper analyzed the environmental impact of energy utilization in agriculture in India and Pakistan. More specifically, the study analyzes the trends of fuel and electricity consumption for crop production in these countries during a ten-year period between the years 2002 and 2011. Life cycle impact assessment categories including global warming potential, human toxicity, acidification and eutrophication were used to holistically analyze the end-user impact of energy consumption. Results indicated an increase in these impacts for both countries during the study period. On a per hectare basis, the assessed impacts were relatively greater in India than in Pakistan during the study period. The main reason behind larger impacts in India was its significantly greater use of coal for electricity generation. Overall, this study showed that further electrification of agriculture will not necessarily lead to cleaner environment in these countries. Due to high population growth rates, energy consumption for agriculture is expected to grow in these countries in the future. Unless cleaner sources of electricity are used, further energy intensification in agriculture will be detrimental to ecosystem and human health, which in turn will be counterproductive for sustainable agriculture.

[A new isoflavone derivative from Rosa Damascena and its antibacterial activity].

A new isoflavone derivative was isolated from Rosa damascena by using various chromatographic techniques including silica gel, Sephadex LH-20, and preparative RP-HPLC separation. Its structure was identified as 4'-hydroxy-7-(3-hydroxypropanoyl)-6-methoxy-isoflavone using combined examinations of their UV, IR, MS, and NMR spectroscopic data. Biological activity test showed that this compound showed prominent antibacterial activity with MIC90 value of (46±4) mg·L⁻¹ for methicillin resistant Staphylococcus aureus(MRSA) strain. This value is close to that of levofloxacin [with MIC90 value (53±5) mg·L⁻¹].

Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function.

BACKGROUND: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. METHODS: After intragastric administration of TXL (0.1 ml/10 g body weight) to C57BL/6J wild-type mice (n = 8) and ApoE-/- mice (n = 8), total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate (HR), left ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and left ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity (PSV), end diastolic flow velocity, and mean flow velocity (MFV) were measured. The pulsatility index (PI) and resistant index were calculated in order to evaluate the vascular elasticity and resistance. The endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor (VEGF). Immunohistochemical detection was performed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P < 0.05 was considered statistically significant. RESULTS: Although there was no significant decrease of cholesterol level (F = 2.300, P = 0.240), TXL inhibited the level of triglyceride and VLDL (F = 9.209, P = 0.024 and F = 9.786, P = 0.020, respectively) in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS (all P < 0.05). TXL enhanced aortic PSV and MFV (F = 10.774, P = 0.024 and F = 11.354, P = 0.020, respectively) and reduced PI of ApoE-/- mice (1.41 ± 0.17 vs. 1.60 ± 0.17; P = 0.037). After incubation with 10 µmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% ± 3%, significantly higher than control group mice (F = 9.280, P = 0.040). TXL also restrain the angiogenesis of ApoE-/- mice aorta (F = 21.223, P = 0.010). Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice (54.0 ± 3.0/mm2 vs. 75.0 ± 2.0/mm2; F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mm2 vs. 54.0 ± 3.0/mm2; F = 11.929, P = 0.020) in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot (F = 20.247, P = 0.004). CONCLUSIONS: TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat to lessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity; improves endothelium-dependent vasodilatation; restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.

Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR α/γ activity in microvascular endothelial cells.

Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPARα/γ-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), ± different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10(-8) and 10(-7) M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 ± 13%, p<0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2 inhibitor PD98059 and the PPARα/γ antagonist GW9662. A ≥ 24 hour exposure to 50 µM DHA or EPA, but not other FA, blunted both the constitutive (by 23 ± 3% and 29 ± 2%, respectively, p<0.05 for both) and insulin-induced CD36 expressions (by 45 ± 27 % and 12 ± 3 %, respectively, p<0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPARα/γ and NF-κB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy.

Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway.

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 µg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.

Nitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications.

Traditional Chinese medicine (TCM) has been used for centuries to treat and prevent certain ailments and diseases. Although TCM has served as mainstream medical care throughout Asia for many generations, it is considered an alternative medical system in much of the Western world. Because many TCMs are used primarily for cardiovascular indications characterized by a nitric oxide (NO) insufficiency, we hypothesized that some, if not all, of these TCMs have a robust NO bioactivity that may act to restore NO homeostasis. We tested a group of convenience samples of TCMs obtained in the United States for endogenous nitrite, nitrate, nitroso, and nitrite reductase activity as well as their ability to relax isolated aortic rings. The results from this study reveal that all of the TCMs tested reveal NO bioactivity through their inherent nitrite and nitrate content and their ability to reduce nitrite to NO. Many of the TCM extracts contain a nitrite reductase activity greater by 1000 times that of biological tissues. Repletion of biological nitrite and nitrate by these extracts and providing a natural system for NO generation in both endothelium-dependent and -independent mechanisms may account for some of the therapeutic effects of TCMs.

[Randomized controlled clinical study on ginger-partitioned moxibustion for patients with cold-damp stagnation type primary dysmenorrhea].

OBJECTIVE: To observe the effect of ginger-partitioned moxibustion in the treatment of patients with primary dysmenorrhea (PD) of cold-damp stagnation type. METHODS: A total of 209 PD patients were randomized into moxibustion group (n=105) and control group (medication group, n=104). Patients of the former group were treated with ginger-partitioned moxibustion at Shenque (CV 8) and Guanyuan (CV 4), once daily for 3 days in the first menstrual cycle, and 3 days before menstruation and once daily for 6 days in the 2nd and 3rd menstrual cycles, and those of control group were asked to take Yueyueshu Granules (a Chinese herbal patent drug for relieving PD). Clinical symptom scores were assessed before and after the treatment. RESULTS: After the treatment, of the 105 and 104 cases in the moxibustion and control groups, the cured, markedly effective, effective and failed cases were 58 (55.24%) and 32 (30.77%), 37 (35.24%) and 33 (31.73%), 5 (4.76%) and 24 (23.08%), and 5 (4.76%) and 15 (14.42%), respectively. The total therapeutic effect of moxibustion group wassignificantly better than that of control group (P<0.01). The effects of moxibustion for relieving mild, moderate and severe dysmenorrhea were evidently superior to those of medication (P<0.01). The symptom scores after the treatment and 3 months of post-treatment in moxibustion group were significantly lower than those of control group (P<0.01). CONCLUSION: Ginger-partitioned moxibustion therapy was effective for PD of cold-damp stagnation type.