Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Extracellular vesicle-mediated ferroptosis, pyroptosis, and necroptosis: potential clinical applications in cancer therapy.

Extracellular vesicles (EVs) have gained increasing recognition as significant regulators of intercellular communication in various physiological and pathological processes. These vesicles play a pivotal role in cancer progression by facilitating the transfer of diverse cargoes, including lipids, proteins, and nucleic acids. Regulated cell death (RCD), the orderly and autonomous death of cells, is controlled by a variety of biomacromolecules and, in turn, influences various biological processes and cancer progression. Recent studies have demonstrated that EV cargoes regulate diverse oncogenes and tumor suppressors to mediate different nonapoptotic forms of RCD, notably ferroptosis, pyroptosis, and necroptosis. Nevertheless, comprehensive exploration of EV-mediated nonapoptotic RCD forms in the context of cancer has not been performed. This review summarizes the progress regarding the biological functions and underlying mechanisms of EVs in mediating nonapoptotic RCD by delivery of cargoes to regulate tumor progression. Additionally, the review delves into the potential clinical applications of EV-mediated cell death and its significance in the areas of cancer diagnosis and therapy.

Adipose-Derived Stem Cell Exosomes and Related microRNAs in Atherosclerotic Cardiovascular Disease.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death from noncommunicable diseases worldwide. The pathological development of ASCVD begins with atherosclerosis, followed by the narrowing and occlusion of the vascular lumen and, subsequently, ischemic necrosis in coronary arteries. Preventing atherosclerosis development and delaying ischemia progression may be effective ways of pre-diagnosing and treating ASCVD. Studies have demonstrated that exosomes from adipose-derived stem cells play an increasingly important role in basic research on cardiovascular diseases in terms of the impact of macrophage polarization and the endothelial, anti-apoptosis, and angiogenesis effects. The related microRNAs play a significant role in ASCVD. This study was novel in reviewing the role of exosomes from adipose-derived stem cells and related microRNAs in ASCVD. Therapeutic potentials of adipose-derived stem cell exosomes in terms of their impact on macrophage polarization, endothelial effect, anti-apoptosis intervention, and angiogenesis.

Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis.

BACKGROUND: In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI). METHODS: Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis. RESULTS: A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P = .008) were significantly higher with TT. CONCLUSIONS: DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.

Discontinuing Aspirin After Short Term Use Versus Continuous Use with a P2Y12 Inhibitor for the Treatment of Patients with Type 2 Diabetes Mellitus Following Percutaneous Coronary Intervention: A Meta-analysis.

INTRODUCTION: In this analysis, we aimed to compare the efficacy and safety of discontinuing aspirin (ASA) after short-term use versus its continuous use with a P2Y12 inhibitor for the treatment of patients with type 2 diabetes mellitus (T2DM) following percutaneous coronary intervention (PCI). METHODS: From May to June 2020, electronic databases were searched for related publications. The cardiovascular and bleeding outcomes representing efficacy and safety, respectively, were the endpoints of this study. The new RevMan software version 5.4 was used to analyze the data. Risk ratios (RR) and 95% confidence intervals (CI) were used to represent the results following data analysis. RESULTS: A total of 9774 participants with T2DM were included in this analysis, whereby 4941 patients were assigned to the ASA discontinuation group and 4833 patients to the dual antiplatelet (DAPT) group. Our result showed that compared to a longer duration (12 months) of DAPT (ASA + P2Y12 inhibitor) use in these patients with T2DM, discontinuing ASA after short-term use (1-3 months) thereafter using only a P2Y12 inhibitor (mono-therapy) was not associated with a significant increase in the risk of major adverse cardiovascular and cerebrovascular events (RR 0.92, 95% CI 0.76-1.12; P = 0.39), myocardial infarction (RR 0.98, 95% CI 0.75-1.26; P = 0.86), all-cause mortality (RR 0.78, 95% CI 0.60-1.02; P = 0.07), cardiac death (RR 0.76, 95% CI 0.43-1.35; P = 0.35), stroke (RR 1.06, 95% CI 0.67-1.67; P = 0.80) and stent thrombosis (RR 0.98, 95% CI 0.58-1.65; P = 0.93). However, discontinuing ASA after short-term use in these patients with T2DM was associated with a lower risk of bleeding defined according to the Academic Research Consortium (BARC) type 2-5 (RR 0.55, 95% CI 0.41-0.73; P = 0.0001), and thrombolysis in myocardial infarction (TIMI) defined as major (RR 0.55, 95% CI 0.41-0.75; P = 0.0001) and minor bleeding (RR 0.58, 95% CI 0.43-0.78; P = 0.0004). CONCLUSION: Discontinuing ASA after short-term use for the treatment of patients with T2DM following PCI was not associated with any increased cardiovascular outcomes. Also, discontinuing ASA after short-term use and continuing the use of a P2Y12 inhibitor were somewhat safer in these patients with T2DM. Further research should follow.

Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating From the Proximal Left Anterior Fascicle.

BACKGROUND: Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC's characteristics. METHODS: Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC. RESULTS: The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms, P=0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms, P<0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm, P=0.002, and 3.9±0.8 versus 15.7±7.8 mm, P<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V5, and V6; lower R wave in leads I, aVR, aVL, V1, V2, and V4; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity. CONCLUSIONS: PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.

PD-1/PD-L1 in cardiovascular disease.

The PD-1/PD-L1 coinhibitory pathway has critical roles in the immune response and autoimmunity via the regulation of T cell activity. Excessive activity and high expression of this pathway suppresses the function of T cells and immunity. Recent research has indicated that tumour cells express high levels of PD-L1, which has an immunosuppressive effect and can result in treatment failure. Anti-PD-L1 or anti-PD-1 agents have well-established beneficial effects on mortality and quality of life in cancer patients. Based on the regulatory effects and therapeutic value of the PD-1/PD-L1 pathway in malignant disorders, we propose that it also regulates cell immunity and in CHD and atherosclerosis. Low expression level of PD-1/ PD-L1 or anti-PD-1/PD-L1 therapy accelerates the immune processes in CHD and aggravates disease according to numerous studies. A few studies have provided strong evidence that changes in the expression levels of PD-1 or PD-L1 can alter the degree of inflammation and the state of coronary plaques in atherosclerosis. In this review, we summarise the alterations of the PD-1/PD-L1 pathway and discuss its role in CHD.

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention: A systematic review and Meta-Analysis (2007-2017).

BACKGROUND: Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI. METHODS: Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software. RESULTS: A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67-1.03; P = .09), (OR: 0.64, 95% CI: 0.41-1.01; P = .06), (OR: 0.77, 95% CI: 0.57-1.03; P = .08), (OR: 0.85, 95% CI: 0.57-1.26; P = .42) and (OR: 0.70, 95% CI: 0.47-1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30-1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01-2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87-3.72; P = .00001). CONCLUSION: Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.

Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability.

BACKGROUND/AIMS: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. METHODS: IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis in vitro and in vivo was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18Rα and p-Smad3 were measured by Weston blotting. RESULTS: Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4+ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells in vivo. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. CONCLUSION: IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease.

Sestrin2 Suppresses Classically Activated Macrophages-Mediated Inflammatory Response in Myocardial Infarction through Inhibition of mTORC1 Signaling.

Myocardial infarction (MI) triggers an intense inflammatory response that is essential for dead tissue clearance but also detrimental to cardiac repair. Macrophages are active and critical players in the inflammatory response after MI. Understanding the molecular mechanisms by which macrophage-mediated inflammatory response is regulated is important for designing new therapeutic interventions for MI. In the current study, we examined the role of Sestrin2, which is a stress-inducible protein that regulate metabolic homeostasis, in the regulation of inflammatory response of cardiac macrophages after MI. We found that cardiac macrophages upregulated Sestrin2 expression in a mouse MI model. Using a lentiviral transduction system to overexpress Sestrin2 in polarized M1 and M2 macrophages, we revealed that Sestrin2 predominantly functioned on M1 rather than M2 macrophages. Sestrin2 overexpression suppressed inflammatory response of M1 macrophages both in vitro and in vivo. Furthermore, in the mouse MI model with selective depletion of endogenous macrophages and adoptive transfer of exogenous Sestrin2-overexpressing macrophages, the anti-inflammatory and repair-promoting effect of Sestrin2-overexpressing macrophages was demonstrated. Furthermore, Sestrin2 significantly inhibited mTORC1 signaling in M1 macrophages. Taken together, our study indicates the importance of Sestrin2 for suppression of M1 macrophage-mediated cardiac inflammation after MI.

mTORC1 signaling is crucial for regulatory T cells to suppress macrophage-mediated inflammatory response after acute myocardial infarction.

Post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction (MI). Supression of post-infarction inflammation would be a logical approach of alleviating post-infarction injury and promoting cardiac repair. In this study, we investigated the significance of mTORC1 signaling in the anti-inflammatory activity of regulatory T cells (Tregs) after MI. Using the murine MI model with wild type and Rag1(-/-) mice, we found that the mechanistic target of rapamycin compex 1 (mTORC1) signaling was upregulated in Tregs infiltrating into the infarcted myocardium, rather than in circulating Tregs after MI. The anti-inflammatory activity of infiltrating Tregs was significantly stronger than that of circulating Tregs. This was demonstrated by a higher expression of anti-inflammatory cytokines in the infiltrating Tregs and a robust suppression of proinflammatory cytokine production by macrophages. In an adoptive transfer analysis, compared with normal splenic Tregs, rapamycin-treated splenic Tregs ineffectively suppressed the post-infarction inflammatory response of infiltrating macrophages. In addition, in vitro cultured primary cardiomyocytes treated with mild oxygen glucose deprivation induced mTORC1 activation and a higher anti-inflammatory activity of Tregs in a coculture assay. Our study identified a new mechanism by which infiltrating Tregs subdue post-infarction inflammation. Understanding and utilizing this information would be helpful for designing new therapeutic interventions for MI.

Combination of D942 with curcumin protects cardiomyocytes from ischemic damage through promoting autophagy.

Myocardial ischemia is one of the main causes of sudden cardiac death. Autophagy has been demonstrated to protect cardiomyocytes from ischemia/reperfusion (I/R)-induced damage. A small molecule compound 5-(3-(4-(2-(4-fluorophenyl)ethoxy)phenyl)propyl)furan-2-carboxylic acid (D942) has been previously shown to specifically activate adenosine monophosphate-activated protein kinase (AMPK) in cancer cells. Another reagent, curcumin, has been shown to inhibit mammalian target of rapamycin (mTOR) signal pathway in tumor cells. Since AMPK signaling induces autophagy, while mTOR signaling inhibits autophagy, here we tested the potential protective efficacy of D942 with curcumin for cardiomyocytes under oxygen-glucose deprivation and reoxygenation (OGD/R). Mouse neonatal cardiomyocytes were treated with D942 and curcumin after being subjected to OGD/R. Cell survival and autophagy-related signal pathways were measured after treatment. Our data indicated both D942 and curcumin enhanced cell survival after OGD/R. The D942 and curcumin induced autophagy in cardiomyocytes through activating AMPK pathway or inhibiting mTOR signaling. Induction of autophagy by D942 and curcumin was the cause of cardioprotection, since inhibition of autophagy abolished the protective efficacy. Furthermore, combination treatment with D942 and curcumin profoundly upregulated autophagy after OGD/R and significantly promoted cell survival. Treatment with D942 and curcumin significantly upregulated autophagy in a murine myocardial I/R model. Taken together, our research suggests that D942 and curcumin could be promising therapeutic agents for myocardial I/R.

The effect of meditation on physical and mental health in junior college students: a quasi-experimental study.

BACKGROUND: Physical stress and mental stress are increasingly common phenomena in our rapidly changing and stressful modern society. Research has found meditation to produce positive and demonstrable stress reduction effects on brain and immune functions. This study is grounded in traditional Chinese philosophical mores that teach a process summarized by the keynote activities of "calm, still, quiet, consider, and get" and the potential of this process to reduce stress in adolescents. PURPOSE: The purpose of this study was to examine the effects of meditation on the physical and mental health of junior college students. METHODS: This research employed a quasi-experimental design. Participants included 242 freshmen from a junior college in Taiwan selected using a convenience sampling technique. Participants were then randomly separated into experimental (n = 119) and control (n = 123) groups. The project duration was 18 weeks, during which the experimental group received 2 hours of meditation treatment per week, for a total of 36 hours. Both groups completed pretest and posttest Life Adaptation Scale forms, which included questionnaires addressing information on physical and mental distress and positive and negative coping strategies. Data were analyzed using analysis of covariance. RESULTS: Findings showed that the effect of the experiment treatment was significant when student physical and mental distress pretest scores were controlled. Physical and mental symptoms in the experimental group were lower than those in the control group. CONCLUSIONS: Meditation can help students to adapt to life stressors. This study also provides support for traditional Chinese wisdom, which promotes meditation as one way to improve health.

Spiritual intelligence of nurses in two Chinese social systems: a cross-sectional comparison study.

BACKGROUND: The spirituality of healthcare providers and their clients is becoming a crucial issue in a world increasingly preoccupied with material issues. In light of such, how do nurses enhance their spiritual intelligence against such materialist pressures? After a 60-year separation of Chinese on both sides of the Taiwan Strait and the rancor between their two governments, what are the similarities and the differences in nurse spirituality profiles between these two different societies? With increasing contact between the two, this issue should be examined and explored, as it has the potential to become an essential unspoken element underpinning holistic care quality. PURPOSE: The purpose of this study was to compare spiritual intelligence between nurses in two different Chinese societies. METHODS: A cross-sectional descriptive and inferential study was conducted at five medical centers in China and Taiwan. A total of 524 registered hospital nurses were recruited as participants. We used R. N. Wolman's (2001) self-reported PsychoMatrix Spirituality Inventory to measure participant levels of spiritual intelligence. The PsychoMatrix Spirituality Inventory incorporated seven factors, including divinity, mindfulness, extrasensory perception, community, intellectuality, trauma, and childhood spirituality. RESULTS: Results showed that social systems did have an impact on nurses' spiritual intelligence. Childhood spirituality and religious beliefs and activities greatly affected and effectively predicted nurses' spiritual intelligence. Nurses on either side of the Taiwan Strait all reported a need to deal with their daily lives pragmatically, objectively, and rationally and relied on empirical evidence in work settings. CONCLUSIONS: As social and economic contacts increase across the Taiwan Strait, it is imperative that nurses adopt cultural awareness and sensitivity as they provide holistic care to clients. This study opens doors to dialogue about and a better understanding of nurses' spiritual intelligence in Taiwan and China.

[People, the environment and health: the "Oneness" of human health from the perspective of universal life presented in "Changes"].

This paper aimed to expand the paradigm of nursing and expand the essential factors of nursing theories beyond "environment" to encompass universal life. While individuals live between the sky and earth, we are an inseparable part of the universe. "Health" is derived from a oneness that embraces the body, mind and spirit. The human body contains the wisdom of the universe, known in Chinese philosophy as the wisdom of "Changes". The body has its own consciousness and possesses great powers of self-healing. Healthiness is the original condition of life. Modern medicine assumes sickness to be a natural phenomenon, with the essential nature of "Changes" neglected as a universal law for maintaining health. Dr. Sun, a renowned physician from the Tang Dynasty, was quoted as saying "Knowing Changes is the prerequisite of knowing medicine." Another saying holds that, "Every word and every sentence in the Book of Changes is an indicator of medicine." Much emphasis has been placed on the relationship between "Changes" and "medicine" in the past. This paper elaborates the relationship between nature and human health in order to provide a clear understanding of the nature of true health, described from the perspectives of medicine and "Changes", an evaluation of modern medical science and the oneness of body-mind-spirit, which is the reality of health. The human body is thus a reflection of the mind and spirit, while the mind and spirit is the "inner body". The body is a highly intelligent organism that truly reflects our inner world. Our inner world is also displayed through physical symptoms. As human suffering is caused by separation from our inner life, the only path to enjoying a healthy and joyful life is to achieve a oneness between our body-mind-spirit. Such is a universal law, which is called "Changes" or "Oneness".

Toll-like receptor-4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome.

Atherosclerosis is an inflammatory disease in which dendritic cells have been suggested to play an essential role. The underlying signalling mechanisms are unknown thus far. The family of Toll-like receptors (TLRs) initiates innate immune responses, and Toll-like receptor-4 (TLR4) has been considered to be an important player in the initiation and progression of atherosclerotic disease. The highly conserved mitogen-activated protein kinase (MAPK) family is one of the major kinase families that regulate cells by transducing extracellular into cellular responses. Three important members of this family are the extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The aim of the study was to investigate the expression of TLR4 and MAPK families on dendritic cells (DC) in patients with coronary arteriosclerosis disease. We have examined the expression of TLR4 protein and mRNA by flow cytometry and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of MAPK family proteins have been determined by Western blot analysis. We examined the expression level of CD80 to value the maturation state of DC. We compared the levels of cytokines in DC in response to lipopolysaccharide (LPS). The results showed that the expression of TLR4 and MAPK families are increased in the patients with acute coronary syndrome (ACS), compared with it in the patients with stable angina and controls. DC in ACS are activated evaluated by its mature marker and cytokine secreting responding to LPS. We suggest that TLR4 and MAPK families maybe involved in activation of circulating DC of ACS patients.

Changes of CD4+CD25+ regulatory T cells in patients with acute coronary syndrome and the effects of atorvastatin.

The function of CD4(+)CD25(+) regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-beta1 and IFN-gamma) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P<0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P<0.01), IFN-gamma levels were increased and IL-10 and TGF-beta1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-gamma was decreased significantly, while IL-10 and TGF-beta1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-beta1, but negatively with serum IFN-gamma and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.

A study of nurses' spiritual intelligence: a cross-sectional questionnaire survey.

BACKGROUND: Nurse's spiritual well-being may assure a positive attitude toward spiritual care, and assist patients in overcoming spiritual distress. Spirituality is often related to one's belief system. Spirituality on the part of nurses is yet largely unheard of in a society with materialism which is one of the most destructive belief systems on the world. OBJECTIVES: The objective of the study was to explore the profile of spiritual intelligence among nurses, and to examine the effect of religions on nurses' spiritual intelligence in China. DESIGN: This is a cross-sectional descriptive and inferential designed study. SETTINGS: The study was carried out in a medical center in China. Subjects were widely distributed, throughout seven provinces, with 16 hospital settings. PARTICIPANTS: A total of 130 registered hospital nurses, who were taking part in a 3-day, national nursing quality conference held by the target medical center in China, were recruited by convenience sampling. METHODS: Wolman's (2001) four-point Likert-type Psycho-Matrix Spirituality Inventroy (PSI) was distributed collaboratively during the period of the conference. Upon receiving oral approval from nursing administrators, the author ensured that subjects' responses would remain confidential and that filling out the questionnaire was to be construed as willingness to participate in this study. RESULTS: 1. The majority of nurses (90%) tended to experience numerous instances of physical emotional pain and suffering throughout life. 2. Among the 130 subjects, only seven nurses clearly specified their religions, and religious beliefs accounted for most of the variance in the criterion variable in the study. CONCLUSIONS: Exploring nurses' spiritual profiles, especially for those who seem to be unfamiliar with spiritual matters, is a starting point on the journey to delivering spiritual care. Chinese nurses' spiritual intelligence is only to be excavated. The study draws attention to the diverse culture of the nurses' concepts of spirituality, which is fundamental to the delivery of truly holistic care of humans in a multi-faith society.

The spiritual intelligence of nurses in Taiwan.

The purposes of the study included: (1) defining the profile of nurses' spiritual intelligence; (2) examining the relationship between nurses' demographic characteristics and spiritual intelligence; and (3) exploring the mode of nurses' spiritual intelligence and related factors, among nurses in Taiwan. A cross-sectional descriptive study was designed and administered to 299 hospital registered nurses, who were distributed throughout metropolitan Taipei. Wolman's (2001) PsychoMatrix Spirituality Inventory, a 4-point scaled, self-reported, 49-item questionnaire covering seven spiritual factors (divinity, mindfulness, extrasensory perception, community, intellectuality, trauma, and childhood spirituality) was used to measure nurses' spiritual intelligence. Results showed that nurses' spiritual intelligence was centralized in a moderate degree, while trauma and childhood spirituality were either moderate or high. Age and childhood spirituality were the most significant variables affecting nurses' spiritual intelligence, accounting for 61.4% of the variance in nurses' spiritual intelligence. This study may contribute to a better understanding of the spiritual intelligence profile of nurses and may also help facilitate a program for nurses' spiritual development as well as improve the quality of spiritual care.