Health information needs and feedback of users in the online TCM community.

To improve the information service quality of the online Traditional Chinese Medicine (TCM) community, this study investigated users' information needs, feedback and the relationship between them. Using qualitative content analysis, the basic characteristics of users' needs were obtained. Logistic regression was used to explore the impact of different need characteristics of feedback. The main findings are as follows: 1) Disease consultation, health preservation, professional discussion, knowledge sharing and experience description are the major 5 types of information needs in the online TCM community; 2) Some users provided TCM-related information, such as the tongue image and the TCM four diagnosis; 3) A total of 78.8% of the posts received effective feedback, and the main types of feedback were answering, discussing, inquiring and emotional supporting; 4) Providing enough information can significantly and positively affect whether needs receive effective feedback, suggesting that users can present information about their condition in as many different formats as possible when articulating their needs.

Renin-angiotensin system mechanism underlying the effect of auricular acupuncture on blood pressure in hypertensive patients with phlegm-dampness constitution: Study protocol for a randomized controlled trial.

BACKGROUND: Phlegm-dampness constitution is a traditional Chinese medicine constitution typically associated with essential hypertension. Previous studies have demonstrated that auricular acupuncture effectively decreases blood pressure and adjusts the constitution. However, the mechanism underlying auricular acupuncture's effect is poorly understood. METHODS: A non-blinded, randomized controlled trial will be undertaken between September 2022 and May 2023. Eighty essential hypertensive patients with a phlegm-dampness constitution will be randomly allocated to one of two groups. The intervention group will receive eight weeks of auricular acupuncture and regular use of antihypertensive drugs, while the control group will only receive antihypertensive drugs. The primary outcome will be any mean differences in office systolic blood pressure. The secondary outcomes investigations will include proteins of the renin-angiotensin system, office blood pressure of different genotypes, and phlegm-dampness constitution scores. DISCUSSION: By demonstrating how auricular acupuncture affects the renin-angiotensin system, this research will offer significant new information on the mechanism underlying the action of auricular acupuncture in hypertension. Moreover, the results will provide crucial clinical information on the associations between renin-angiotensin system gene polymorphisms and the antihypertensive effects of auricular acupuncture. TRIAL REGISTRATION: Registered at the chictr.org.

Fine molecular structure and digestibility changes of potato starch irradiated with electron beam and X-ray.

The change of digestibility of starch irradiated with different types from the perspective of fine structure is not well understood. In this work, the change of internal structure, molecular weight and chain-length distribution, helical structure, lamellar structure, fractal structure and digestibility of native and treated potato starch with electron beam and X-ray was analyzed. Two irradiations caused the destruction of internal structure, the disappearance of growth rings and increase of pores. Irradiation degraded starch to produce short chains and to decrease molecular weight. Irradiation increased double helical content and the thickness and peak area of lamellar structure, resulting in the reorganization of amylopectin and increase of structure order degree. The protected glycosidic linkages increased starch resistance to hydrolase attack, thereby enhancing the anti-digestibility of irradiated starch. Pearson correlation matrix also verified the above-mentioned results. Moreover, X-ray more increased the anti-digestibility of starch by enhancing ability to change fine structure.

[Traditional Chinese medicine used as anti-aging agent by targeting nuclear factor erythroid 2-related factor 2 signaling pathway].

The imbalance of redox homeostasis is a major characteristic of aging and contributes to the pathogenesis of various aging-related diseases. As a regulatory hub of redox homeostasis, nuclear factor erythroid 2-related factor 2 (NRF2) can attenuate oxidative stress by activating the transcription of many antioxidant enzymes. China is the birthplace of traditional Chinese medicine (TCM) which has been wildly used as medicine for thousands of years. Recently, TCM as anti-aging medicine has attracted enormous attention. Focusing on the NRF2 signaling pathway, this paper summarizes the correlation between various anti-aging TCM and the NRF2 signaling, and discusses the common key mechanisms by which TCM slows the aging process by targeting the NRF2 signaling network.

Designing and Evaluating an Emotionally Responsive Virtual Patient Simulation.

INTRODUCTION: Virtual patient (VP) simulations have been widely used for healthcare training, education, and assessment. However, few VP systems have integrated emotion sensing and analyzed how a user's emotions may influence the overall training experience. This article presents a VP that can recognize and respond to 5 human emotions (anger, disgust, fear, joy, and sadness), as well as 2 facial expressions (smiling and eye contact). METHODS: The VP was developed by combining the capabilities of a facial recognition system, a tone analyzer, a cloud-based artificial intelligence chatbot, and interactive 3-dimensional avatars created in a high-fidelity game engine (Unity). The system was tested with healthcare professionals at Changzhou Traditional Chinese Medicine Hospital. RESULTS: A total of 65 participants (38 females and 27 males) aged between 23 and 57 years (mean = 38.35, SD = 11.48) completed the survey, and 19 participants were interviewed. Most participants perceived that the VP was useful in improving their communication skills, particularly their nonverbal communication skills. They also reported that adding users' affective states as an additional interaction increased engagement of the VP and helped them build connections with the VP. CONCLUSIONS: The emotionally responsive VP seemed to be functionally complete and usable. However, some technical limitations need to be addressed before the system's official implementation in real-world clinical practice. Future development will include improving the accuracy of the speech recognition system, using more sophisticated emotion sensing software, and developing a natural user interface.

Traditional Chinese Medicine constitution types of high-normal blood pressure: A meta-analysis.

Objective: We determined the distribution of constitutional types of high-normal blood pressure in Traditional Chinese Medicine (TCM) and provided evidence for the prevention of high-normal blood pressure and hypertension. Methods: Eight digital databases were searched from January 2011 to November 2022, including PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP. We performed a meta-analysis with the random-effects model or fixed-effects model to describe the distribution of constitutional types of high-normal blood pressure in TCM. The studies were assessed based on heterogeneity testing and the potential for publication bias. The meta-analysis was performed on Stata software 15.0. Results: A total of 17 studies with 8118 participants were included in this meta-analysis. The proportion of the biased constitution (82.3%; 95% CI: 75.6%-89.1%, p < 0.001) was higher than the balanced constitution (17.3%; 95% CI: 10.7-23.8%, p < 0.001). Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution accounted for 16.0% (95%CI: 10.5-21.5%, p < 0.001), 14.8% (95% CI: 11.0-18.6%, p < 0.001), 11.3% (95% CI: 8.0-14.5%, p < 0.001) of the total high-normal blood pressure cases, respectively. The subgroup analyses performed that region, age and gender were positively associated with the distribution of constitution types of high-normal blood pressure in TCM. Compared with the general population, the risk of high-normal blood pressure in people with the phlegm-dampness constitution, Yin-deficiency constitution, and blood-stasis constitution was 2.665 (95%CI: 2.286-3.106, p < 0.001), 2.378 (95%CI: 1.197-4.724, p = 0.013), 1.965 (95%CI: 1.634-2.363, p < 0.001) times of the general population, respectively. Meanwhile, the risk of high-normal blood pressure was lower in people with a balanced constitution (0.248, 95%CI: 0.165-0.372, p < 0.001). Conclusions: Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution were the common constitution types of high-normal blood pressure. There might also be differences in the distribution characteristics of TCM constitution among people with high-normal blood pressure in different regions, ages, and genders. Finally, a balanced constitution might be a protective factor for hypertensive people.

Obtaining EQ-5D-3L utility index from the health status scale of traditional Chinese medicine (TCM-HSS) based on a mapping study.

BACKGROUND: Almost all traditional Chinese medicine (TCM) quality of life measures are non-preference-based measures (non-PBMs), which do not provide utilities for cost-utility analysis in pharmacoeconomic evaluation. Whereas the mapping has become a new instrument to obtain utilities, which builds a bridge between non-PBMs and PBMs. PURPOSE: To develop mapping algorithms from the health status scale of traditional Chinese medicine (TCM-HSS) onto the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L). METHODS: The cross-sectional data were collected by questionnaire survey from a tertiary hospital visit population and community residents in China, and randomly divided into training and validation set by 2:1. Based on the training set, direct and indirect mapping methods (7 regression methods and 4 model specifications) were conducted to establish alternative models, which were comprehensively evaluated based on the validation set by mean absolute error, root mean square error, and Spearman correlation coefficient between predicted and observed values. Based on the whole sample, the preferred mapping algorithm was developed. RESULTS: A total of 639 samples were included, with an average age of 45.24 years and 61.66% of respondents were female. The mean EQ-5D-3L index was 0.9225 [SD = 0.1458], and the mean TCM-HSS index was 3.4144 [SD = 3.1154]. The final mapping algorithm was a two-part regression model including the TCM-HSS subscales, interaction terms, and demographic covariates (age and gender). The prediction performance was good. The mean error was 0.0003, the mean absolute error was 0.0566, the root mean square error was 0.1039, and 83.10% of the prediction errors were within 0.1; the Spearman correlation coefficient between predicted and observed EQ-5D-3L values was 0.6479. CONCLUSION: It is the first study to develop a mapping algorithm between the TCM-HSS and EQ-5D-3L, which demonstrates excellent prediction accuracy and estimates utility value for economic evaluation from TCM quality of life measures.

A WeChat-based self-compassion training to improve the treatment adherence of patients with schizophrenia in China: Protocol for a randomized controlled trial.

Background: At present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated that increasing a patient's level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia. Methods: The protocol for the randomized controlled trial (RCT) is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline (T0), immediately after the intervention (T1), and 3 weeks after the intervention (T2). Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention (T1). Expected results: The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients' desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries.

Infant exposure to trace elements in breast milk, infant formulas and complementary foods from southern China.

Excessive intake of essential trace elements or exposure to potentially toxic elements above certain thresholds may cause adverse health effects in humans. To date, there is scarce evidence concerning Chinese infant exposure to trace elements and the associated risks. In this study, we collected 61 breast milk, 54 infant formula and 90 complementary food samples from southern China to investigate the levels of cobalt (Co), chromium (Cr), copper (Cu), selenium (Se), zinc (Zn), arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb). The concentrations of these elements in the breast milk samples ranged from under the limit of detection (

Sensitivity Enhancement of Group Refractive Index Biosensor through Ring-Down Interferograms of Microring Resonator.

In recent years, silicon-on-insulator substrates have been utilized for high-speed and low-power electronic components. Because of the high refractive index contrast of the silicon wire, its photonic device footprint can be significantly reduced. Moreover, the silicon photonic process is compatible with a complementary metal-oxide-semiconductor fabrication, which will benefit the high-density optoelectronic integrated circuits development. Researchers have recently proposed using the microring resonator (MRR) for label-free biosensing applications. The high-quality factor caused by the substantial electric field enhancement within the ring makes the MRR a good candidate for biomolecule detection under low analyte concentration conditions. This paper proposes an MRR chip to be a biosensor on the silicon platform through the relative displacement between the spatial ring-down interferograms at various cladding layers. The higher-order ring-down of the spatial interference wave packet will enhance the biosensing sensitivity after optimizing the coupling, MRR length, and the optical source bandwidth at the fixed optical waveguide loss. Finally, a typical sensitivity of 642,000 nm per refractive index unit is demonstrated under 0.1 µW minimum optical power detection for an MRR with a 100 µm radius. Higher sensitivity can be executed by a narrow bandwidth and lower silicon wire propagation loss.

Traditional Chinese Medicine is effective for COVID-19: A systematic review and meta-analysis.

Traditional Chinese Medicine (TCM) has played crucial roles in treating COVID-19 in China. But its effectiveness has not yet been widely realized/recognized over the world. We performed a systematic review and meta-analysis to investigate the clinical efficacy of TCM medicine in the treatment for COVID-19. We obtained the data of COVID-19 and traditional Chinese medicine from PubMed, MEDLINE, Web of Science and other databases, and searched from January 1, 2020 to January 26, 2022 to determine the randomized controlled trials (RCTs) without language restrictions. The review includes 26 randomized clinical trials including 2981 patients. The treatment of COVID-19 by TCM combined with conventional treatment is more effective than by pure conventional treatment in many aspects, including increasing of the effective rate [OR â€‹= â€‹2.47, 95%CI (1.85, 3.30), P â€‹< â€‹0.00001], fever disappearance rate [OR â€‹= â€‹3.68, 95%CI (1.95, 6.96), P â€‹< â€‹0.0001], fatigue disappearance rate [OR â€‹= â€‹3.15, 95%CI (1.60, 6.21), P â€‹= â€‹0.0009], cough disappearance rate [OR â€‹= â€‹2.89, 95%CI (1.84, 4.54), P â€‹< â€‹0.00001], expectoration disappearance rate [OR â€‹= â€‹5.94, 95%CI (1.98, 17.84), P â€‹= â€‹0.001], disappearance rate of shortness of breath [OR â€‹= â€‹2.57, 95%CI (1.13, 5.80), P â€‹= â€‹0.02], improvement rate of CT image [OR â€‹= â€‹2.43, 95%CI (1.86, 3.16), P â€‹< â€‹0.00001], and reduction of the hospitalization time [MD â€‹= â€‹-3.16, 95%CI (-3.75, -2.56), P â€‹< â€‹0.00001], and deterioration rate [OR â€‹= â€‹0.49, 95%CI (0.29, 0.83), P â€‹= â€‹0.007]. The findings of this meta-analysis suggest that TCM can effectively relieve symptoms, boosted patients' recovery, cut the rate of patients developing into severe conditions, and reduce the deterioration rate.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF-κB/NLRP3 Axis.

BACKGROUND: Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. METHODS: In vitro and in vivo models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry. RESULTS: Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats. CONCLUSION: Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/NLRP3 axis, indicating a potential therapeutic function in DN.

Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 ß/ß-Catenin Pathway by Restoring Autophagic Activity.

BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the result of high glucose-induced pathological changes in podocytes, such as epithelial-mesenchymal transition (EMT). Autophagy is an important mechanism of podocyte repair. Ginsenoside Rg1, the active ingredient of ginseng extract, has antifibrotic and proautophagic effects. Therefore, we hypothesized that ginsenoside Rg1 can reverse podocyte EMT via autophagy and alleviate DN. AIM: This study aimed to investigate the effect of ginsenoside Rg1 on DN rats and high glucose-induced podocyte EMT by regulating the AKT/GSK3ß/ß/. METHODS: Diabetic rats induced by STZ injection were treated with 50 mg/kg ginsenoside Rg1 for 8 weeks, and the renal functional, metabolic, and histopathological indices were evaluated. DN was simulated in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed in vivo and in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed. RESULTS: Ginsenoside Rg1 significantly alleviated renal fibrosis and podocyte EMT in diabetic rats, and podocytes exposed to high glucose levels, which was abolished by the autophagy inhibitor 3-MA. Furthermore, ginsenoside Rg1 regulated the AKT/GSK3 ß/ß/. CONCLUSION: Ginsenoside Rg1 alleviated podocyte EMT by enhancing AKT/GSK3ß/ß-catenin pathway-mediated autophagy, indicating its therapeutic potential for DN and other glomerular diseases.ß/ß/.

Ligustrum robustum Intake, Weight Loss, and Gut Microbiota: An Intervention Trial.

Ligustrum robustum (LR) shows antiobesity effects in animal studies. However, little is known about the effect on human. The present study aimed to investigate the effect of LR intake on weight change in obese women and the role of gut microbiota. Thirty overweight and obese female participants (BMI ≥24 kg/m2) were recruited in the current study. The participants drank LR 10g/d for 12 wks. Their body composition and related biomarkers were assessed. Alterations of the gut microbiota were analyzed using 16S rRNA sequencing. The primary outcome was the change in body weight. LR intake resulted in 2.5% weight loss over 12 wks (P<0.01). Change in body fat at 12 wk was -1.77 ± 1.19 kg (P<0.01). In addition, decreased Firmicutes-to-Bacteroidetes ratio (P=0.03), increased richness (the ACE estimator, P<0.01; the Chao1 estimator, P<0.01), and altered representative taxa of the gut microbiota were observed. Bacteroidaceae, Bacteroides, Bacilli, and Lactobacillales were higher while Ruminococcaceae, Enterobacteriaceae, Enterobacteriales, Lachnospiraceae, Clostridia, and Clostridiales were lower at 12 wk. Moreover, LR intervention decreased fasting glucose (P<0.01), serum leptin (P<0.01), and IL8 (P=0.02) and increased HOMA-ß (P<0.01). LR intervention moderately decreased the body weight in overweight and obese women and such effect might be due to modulation of gut microbiota.

Multi-technical analysis on the antioxidative capacity and total phenol contents of 94 traditional Chinese dietary medicinal herbs.

Dietary medicinal herbs (DMHs) are superior reservoirs for natural antioxidants and safe for long-term consumption. Chinese government recently announced an official list of traditional Chinese DMHs to support civil health promotion. However, antioxidative capacity (AOC) and total phenol contents (TPC) of these listed herbs were not comprehensively and systematically evaluated. In this study, AOC of 94 listed DMHs in water extract were investigated by three techniques including radical scavenging and ferric reducing antioxidative power. The results showed that emblic leafflower, rose, and clove possessed the highest AOC, while TPC was significantly correlated with AOC. While traditional Chinese medicines are categorized by the nature of Yin-Yang, this study demonstrated that Yin DMHs are statistically correlated with high AOC. Practical application: In this study, AOC and TPC of 94 traditional Chinese DMHs were documented systematically. Emblic leafflower, rose and clove were shown to possess the highest AOC. TPC in traditional Chinese DMHs was significantly correlated with the AOC, while DMHs with Yin characteristic might be used as an indicator to identify potential antioxidative herbs.

A new Secondary metabolites of the crinoid (Comanthina schlegeli) associated fungus Alternaria brassicae 93.

Fungus Alternaria brassicae 93 isolated from crinoid (Comanthina schlegeli), which was collected from the South China Sea. Six compounds were isolated from A. brassicae 93, including one new compound (1), along with five known compounds, ochratoxin A methyl ester (2), cis-4-hydroxym-ellein (3), (R)-7-hydroxymellein (4), trans-2-anhydromevalonic (5) and protocatechuic acid (6). Their structures were determined by spectroscopic methods and comparison with reported data. Cytotoxicity against two human cancer cell lines and antibacterial activity against twelve aquatic bacteria of compound 1 were also tested.

Identification and structure-activity relationships of chromene-derived selective estrogen receptor modulators for treatment of postmenopausal symptoms.

As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), novel chromene scaffolds, benzopyranobenzoxapanes, were discovered. Many compounds showed binding affinity as low as 1.6-200 nM, displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line as well in Ishikawa cell line with IC(50) values in the range 0.2-360 nM. On the basis of the side chain substitution, various compounds demonstrated strong inhibitory activity in anti-uterotropic assay. Compound 7-(R) and its major metabolites 5-(R) and 6-(R) were evaluated in several in vivo models of estrogen action. Relative to a full estrogen agonist (ethynyl estradiol) and the SERM raloxifene, 7-(R) was found to be a potent SERM that behaved as antagonist in the uterus and exhibited estrogen agonistic activity on bone, plasma lipids, hot flush, and vagina. The overall pharmacokinetic profile and stability were significantly improved compared to those of the phase 2 development compound 9-(R).