Modern concepts and biomarkers of blood stasis in cardio- and cerebrovascular diseases from the perspectives of Eastern and Western medicine: a scoping review protocol.

OBJECTIVE: The objective of this review is to provide a modern definition and identify potential biomarkers of blood stasis in cardio- and cerebrovascular diseases by mapping, comparing, and combining Eastern and Western concepts. INTRODUCTION: Blood stasis is a pathological concept found in both Eastern and Western medical literature. In traditional East Asian medicine, blood stasis is a differential syndrome characterized by stagnant blood flow in various parts of the body. Similarly, in Western medicine, various diseases, especially cardio- and cerebrovascular diseases, are known to be accompanied by blood stasis. Numerous scientific studies on blood stasis have been conducted over the last decade, and there is a need to synthesize those results. INCLUSION CRITERIA: We will use the keywords "blood stasis," "blood stagnation," "blood stagnant," and "blood congestion" in 3 electronic databases: PubMed, Cochrane CENTRAL, and Google Scholar. In addition, we will use the keywords "어혈" and "혈어" in 4 Korean electronic databases (ie, NDSL, OASIS, KISS, and DBpia). Peer-reviewed articles published from 2010 to the present that focus on blood stasis in cardio- and cerebrovascular diseases in human subjects according to the International Classification of Diseases 11 th revision categories BA00-BE2Z, 8B00-8B2Z, 8E64, and 8E65 will be included. Reviews, opinion articles, in vivo, in vitro, and in silico preclinical studies will be excluded. METHODS: We will follow the frameworks by Arksey and O'Malley and Levac et al. as well as JBI guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Two reviewers will independently search and screen titles and abstracts followed by full-text screening of eligible studies. If there are discrepancies between the 2 reviewers, a third reviewer will be consulted to make the final decision. We will use descriptive narrative, tabular, and graphical displays, and content analysis to present the results. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/gv4ym.

Development of a patient-report pressure algometer for the quantification of abdominal examination.

BACKGROUND: Abdominal examination (AE), one of the primary diagnostic tools used in traditional Korean medicine (TKM), has a limitation of being subjective due to depending on individual practitioner's experience. Therefore, we devised a novel patient-report pressure algometer (PA) and performed a clinical trial to investigate its validity. METHODS: In total, 44 participants with functional dyspepsia and 44 healthy participants completed the study. The participants were allocated into one of two groups according to the existence of abdominal stiffness at 5 acupoints or abdominal tenderness at 12 acupoints diagnosed by TKM doctors. The pressure depth and pressure pain threshold (PPT) were evaluated using the PA at the same acupoints. We assessed the validity (sensitivity and specificity) of PA and calculated the area under the curve (AUC) and optimal cutoff value of the test variables (pressure depth and PPT) to criterion standards (abdominal stiffness and tenderness). RESULTS: Pressure depth and PPT assessed by PA showed high sensitivity and specificity in diagnosing abdominal stiffness and tenderness. The validity at CV-14 of diagnosing abdominal tenderness with PPT by PA had a sensitivity of 73.1%, specificity of 77.8%, and an AUC of 0.807 with a P value of < 0.001. CONCLUSION: This study may provide evidence of standardization and quantification of AE through PA.

Association of Cold-Heat Patterns with Tongue Features, Body Composition, Anthropometric Indices, and Blood Parameters in Tae-Eum Type.

INTRODUCTION: The purpose of this study was to elucidate the relationship between cold-heat patterns and body composition, anthropometric indices, blood parameters, and tongue features in Tae-Eum type subjects. We also sought to determine whether significant indicators could be used as risk factors for predicting cold-heat patterns in a clinic. METHODS: This prospective, case-control pilot study was conducted at a single center. The subjects were males and females aged 19 years or older who had been analyzed as the Tae-Eum type. After screening, subject allocation was performed. The body composition, 11 anthropometric indices, blood parameters, and tongue features of the subjects were measured by well-trained practitioners. An independent t-test was conducted to compare the cold- and heat-pattern groups. Binary logistic regression was performed to determine significant differences between the two groups after adjusting for age, sex, and systolic blood pressure, with a focus on identifying significant indicators. RESULTS: Eighty-nine participants were recruited, 39 of whom were excluded from the analysis. Ultimately, 20 cold-pattern and 30 heat-pattern subjects were included in the final analysis. We found that alanine aminotransferase and all anthropometric indices, except for neck and forehead circumference, were significant predictive factors in both groups according to the binary regression analysis. Additionally, the tongue body color in the cold-pattern group was significantly paler than that in the heat-pattern group. CONCLUSIONS: This study found that cold and heat patterns were significantly associated with body composition, anthropometric indices, blood parameters, and tongue features. We suggest that these factors could thus be used as objective indicators and predictors of cold-heat patterns. Our findings provide fundamental but also applicable data that will be useful for diagnosing and monitoring cold-heat patterns in Tae-Eum type patients.

Effects of Bu-Zhong-Yi-Qi-Tang for the treatment of functional dyspepsia: a feasibility study protocol.

BACKGROUND: Bu-Zhong-Yi-Qi-Tang (BZYQT) has long been used for the treatment of severe weakness caused by general fatigue, loss of appetite, or indigestion. The aim of this feasibility study is to assess the effectiveness and safety of BZYQT for the treatment of functional dyspepsia (FD) with spleen qi deficiency. METHODS: This study will be conducted at a single center as a prospective, nonrandomized, nonblinded, single-arm feasibility study. A total of 30 participants diagnosed with FD in accordance with the Rome III criteria will be enrolled. All patients will receive BZYQT for 4 weeks. The primary outcome is the change in the Nepean Dyspepsia Index-Korean version (NDI-K) scores between the baseline and 4-week images. The secondary outcomes include the tongue coating thickness, blood parameters, and BZYQT Questionnaire score. The NDI-K score will be acquired four times, at Weeks 0 (baseline), 2 (during treatment), 4 (after treatment), and 8 (after follow-up). Written informed consent will be obtained from all study participants prior to enrollment. This study has been approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital. This study protocol is registered with the national clinical trial registry of the World Health Organization International Clinical Trials Registry Platform. Results will be published in a journal and will be disseminated both electronically and in print. DISCUSSION: The results of this study may serve as a guide for researchers seeking to effectively evaluate the effects of BZYQT. TRIAL REGISTRATION NO: KCT0002114 (date of registration: October 21, 2016).

Differences in the Tongue Features of Primary Dysmenorrhea Patients and Controls over a Normal Menstrual Cycle.

BACKGROUND: The aims of this study were to investigate the relationships between tongue features and the existence of menstrual pain and to provide basic information regarding the changes in tongue features during a menstrual cycle. METHODS: This study was conducted at the Kyung Hee University Medical Center. Forty-eight eligible participants aged 20 to 29 years were enrolled and assigned to two groups according to their visual analogue scale (VAS) scores. Group A included 24 females suffering from primary dysmenorrhea (PD) caused by qi stagnation and blood stasis syndrome with VAS ≥ 4. In contrast, Group B included 24 females with few premenstrual symptoms and VAS < 4. All participants completed four visits (menses-follicular-luteal-menses phases), and the tongue images were taken by using a computerized tongue image analysis system (CTIS). RESULTS: The results revealed that the tongue coating color value and the tongue coating thickness in the PD group during the menstrual phase were significantly lower than those of the control group (P = 0.031 and P = 0.029, resp.). CONCLUSIONS: These results suggest that the tongue features obtained from the CTIS may serve as a supplementary means for the differentiation of syndromes and the evaluation of therapeutic effect and prognosis in PD. TRIAL REGISTRATION: This trial was registered with Clinical Research Information Service, registration number KCT0001604, registered on 27 August 2015.

Validation of the qi blood yin yang deficiency questionnaire on chronic fatigue.

BACKGROUND: Chronic fatigue (CF) reflects an imbalance of inter-organ functions or of the four essential physiological components qi, blood (xue), yin, and yang. CF can be subdivided into different patterns. However, there are no diagnostic methods for CF. This study aimed to clinically validate a pattern identification method by identifying correlations between CF and responses to the qi blood yin yang deficiency questionnaire (QBYY-Q). METHODS: Participants were recruited between May and June 2014 through the Kyung Hee University Korean Medicine hospital website and via posters and comprised 129 CF patients diagnosed with the United States Centers for Disease Control and Prevention (1994) criteria. Participants who had organic diseases that explained the CF were excluded. A total of 159 participants were asked to complete the QBYY-Q, the fatigue severity scale, and the Chalder fatigue scale. The latter two questionnaires were used to assess convergent validity with the QBYY-Q. Among the 129 CF participants, 70 and 59 had chronic fatigue syndrome and idiopathic chronic fatigue, respectively. Two Korean medical doctors independently assessed participants' qi, blood, yin, and yang deficiency patterns using QBYY deficiency pattern identification guidelines. Based on the results of a preliminary study of the QBYY-Q, we selected 32 reliable items for symptoms corresponding to each deficiency pattern. The items were used to estimate internal consistency and construct validity. Multinomial logistic regression analysis was performed for scores on each deficiency pattern. RESULTS: The data were means and standard deviations or numbers of participants and proportions for continuous and categorical variables, respectively. A statistical significance level of P < 0.05 was assumed. The QBYY-Q showed satisfactory internal consistency. Explanatory factor analysis extracted two factors for each deficiency pattern. The percentages of explained variance for qi, blood, yin, and yang deficiency were 45.1, 58.0, 52.2, and 63.4 %, respectively. Each QBYY-Q deficiency score was positively associated with each corresponding deficiency pattern. Qi deficiency was used as a reference category. Odds ratios of blood, yin, and yang deficiency were 10.97, 10.69, and 14.64, respectively. CONCLUSION: The QBYY-Q was suitable for estimating the influences of qi, blood, yin, and yang deficiencies in CF. Trial registration This trial was registered with the Korean Clinical Trial Register (KCT0001199).

Quantification of the parameters of twisting-rotating acupuncture manipulation using a needle force measurement system.

BACKGROUND: To date, much research has been conducted to measure needle manipulation quantitatively and objectively. This study was performed to quantitatively measure the differences in the amount of stimulation caused by various rotation frequencies and angles in twisting-rotating acupuncture needle manipulation. METHODS: The torque Z force exerted on a tissue was measured at various rotation frequencies and angles by rotating a needle with a needle force measurement system attached to a needle insertion tissue model. RESULTS: The results show that with rotation frequency at 60°, the torque Z force increased significantly from 0.023 N mm to 0.118 N mm as the rotation angle increased (p < 0.05). In addition, the torque Z force was significantly increased from 0.082 N mm to 0.292 N mm when the rotation angle increased from 60° to 180° at 0.15 Hz. (p < 0.05). A strong linear positive relationship between the torque Z force and rotation angle or frequency was obtained [Pearson correlation coefficient (r) > 0.88; p < 0.001]. CONCLUSION: The change in needle-tissue interaction force by rotating angles showed a tendency to be higher than those by rotation frequency. Further quantitative research on various manipulations will be required for a standardized education on manipulation and stimulation as well as on needle model development to become possible.

Protocol for the evaluation and validation of Qi Blood Yin Yang deficiency pattern questionnaire: prospective observational study.

BACKGROUND: The aim of this study is to validate the pattern identification standard of qi, blood, yin, and yang deficiency patterns diagnosis. The current study will investigate the usefulness of the Qi Blood Yin Yang deficiency pattern questionnaire as a diagnostic tool for qi, blood, yin, and yang deficiencies by assessing the agreement between the scores and a gold standard established by assessors. METHODS: This protocol is for a single center, prospective, observational study. A total of 248 eligible patients with unexplained chronic fatigue will be assigned to four groups in a 1:1:1:1 ratio as the qi deficiency group, blood deficiency group, yin deficiency group, and yang deficiency group. The primary outcome will be measured using the score of the Qi Blood Yin Yang deficiency pattern questionnaire and the secondary outcomes will be measured using the fatigue severity scale, Korean-translated chalder fatigue scale, computerized tongue image analysis system, and three types of pattern identification questionnaires (cold-heat, food accumulation, and seven emotions patterns). The safety of the clinical study will be assessed after measurements at every visit. All statistical analysis will be performed using the R Statistics program. Statistics experts will analyze the relationship between clinical data using the Pearson's Chi-squared test and independent t-test. DISCUSSION: This study will provide reference data and good evidence that are applicable to future studies. Furthermore, the results of the present study are useful to improve the care of patients with unexplained chronic fatigue and unexplained chronic fatigue-related disorders.

Color distribution differences in the tongue in sleep disorder.

Introduction. According to traditional East Asian medicine (TEAM) theory, the tongue represents conditions of qi and blood. In the present study, the relationship between the tongue and the qi and blood in conditions with no apparent disease was investigated. Methods. A total of 454 elderly people with no apparent disease were recruited. Two Korean oriental medicine doctors classified subjects into a normal group (n = 402) and a sleep disorder group (n = 52). Three to five weeks after the experiment, 153 subjects were rerecruited for a second experiment. Two-dimensional color histograms, whose seven variables represent the color distribution in Commission Internationale de l'Éclairage 1976 (L∗, a∗, b∗) color space, were produced from tongue images. Results. The color of the tongue body in the sleep disorder group appeared paler than that in the normal group, and the tongue coating in the normal group was less widely distributed compared with that in the sleep disorder group. The differences in tongue color between the normal at first experiment and sleep disorder at second experiment conditions were similar to the differences between the normal and the sleep disorder groups. Conclusions. The tongue states in the sleep disorder group indicate a qi and blood deficiency according to TEAM theory.

Constitution-specific features of perspiration and skin visco-elasticity in SCM.

BACKGROUND: Human skin properties have been used as an important diagnostic component in traditional medicine as they change with health conditions. Sasang constitutional medicine (SCM) puts emphasis on the recognition of the constitution-specific skin features prior to the diagnostic decision of health. In this work, in search of skin-characteristics effectively reflecting SCM features, we compared several skin properties such as perspiration, visco-elasticity, elasticity, and elasticity hysteresis, in several candidate body parts. METHODS: We conducted a clinical study in which a total of 111 healthy females aged 50 - 70 years participated with their Sasang constitution (SC) types determined objectively by the Sasang constitutional analytic tool. Perspiration on the skin surface was estimated by using a capacitance sensor to measure the amount of moisture on the palm, forehead, and philtrum before and after a heating stimulus. We acquired the visco-elasticity, elasticity, and elasticity hysteresis at the forearm by Dermalab's elasticity sensing device. An analysis of covariance (ANCOVA) was conducted to evaluate the effect of SC on the nine skin features acquired. RESULTS: The visco-elasticity of the forearm of the Soeum-in (SE) group was significantly lower than that of the Taeeum-in (TE) group (F = 68.867, p < 0.001), whereas the elasticity hysteresis of the SE group was higher than that of the TE group (F = 10.364, p < 0.01). The TE group had more perspiration on the forehead than the SE group (F = 9.050, p < 0.01). The SE group had a large perspiration difference between the philtrum and the forehead compared with the TE group (F = 7.892, p < 0.01). CONCLUSIONS: We found four significant skin features that reflect the inherent constitutional attributes of the TE and SE groups in accordance with SCM literature; the visco-elasticity, elasticity hysteresis, perspiration on the forehead and philtrum. Our findings are based on a novel interpretation of the SCM literature and will contribute to developing the constitutional health status evaluation system in SCM.

A practical approach to Sasang constitutional diagnosis using vocal features.

BACKGROUND: Sasang constitutional medicine (SCM) is a type of tailored medicine that divides human beings into four Sasang constitutional (SC) types. Diagnosis of SC types is crucial to proper treatment in SCM. Voice characteristics have been used as an essential clue for diagnosing SC types. In the past, many studies tried to extract quantitative vocal features to make diagnosis models; however, these studies were flawed by limited data collected from one or a few sites, long recording time, and low accuracy. We propose a practical diagnosis model having only a few variables, which decreases model complexity. This in turn, makes our model appropriate for clinical applications. METHODS: A total of 2,341 participants' voice recordings were used in making a SC classification model and to test the generalization ability of the model. Although the voice data consisted of five vowels and two repeated sentences per participant, we used only the sentence part for our study. A total of 21 features were extracted, and an advanced feature selection method-the least absolute shrinkage and selection operator (LASSO)-was applied to reduce the number of variables for classifier learning. A SC classification model was developed using multinomial logistic regression via LASSO. RESULTS: We compared the proposed classification model to the previous study, which used both sentences and five vowels from the same patient's group. The classification accuracies for the test set were 47.9% and 40.4% for male and female, respectively. Our result showed that the proposed method was superior to the previous study in that it required shorter voice recordings, is more applicable to practical use, and had better generalization performance. CONCLUSIONS: We proposed a practical SC classification method and showed that our model having fewer variables outperformed the model having many variables in the generalization test. We attempted to reduce the number of variables in two ways: 1) the initial number of candidate features was decreased by considering shorter voice recording, and 2) LASSO was introduced for reducing model complexity. The proposed method is suitable for an actual clinical environment. Moreover, we expect it to yield more stable results because of the model's simplicity.

The concept of sasang health index and constitution-based health assessment: an integrative model with computerized four diagnosis methods.

SASANG CONSTITUTIONAL MEDICINE (SCM) SHARES ITS PHILOSOPHY WITH THAT OF PERSONALIZED MEDICINE: it provides constitution-specific treatment and healthcare individualized for each patient. In this work, we propose the concept of the Sasang Health Index (SHI) as an attempt to assess the individualized health status in the framework of SCM. From the target population of females in their fifties and older, we recruited 298 subjects and collected their physiological data, including complexion, radial pulse, and voice, and their questionnaire responses. The health status of each subject was evaluated by two Korean medical doctors independently, and the SHI model was obtained by combining all the integrative features of the phenotype data using a regression technique. As a result, most subjects belonged to either the healthy, subhealthy, or slightly diseased group, and the intraclass correlation coefficient between the two doctors' health scoring reached 0.95. We obtained an SHI model for each constitution type with adjusted R-squares of 0.50, 0.56, and 0.30, for the TE, SE, and SY constitution types, respectively. In the proposed SHI model, the significant characteristics used in the health assessment consisted of constitution-specific features in accordance with the classic literature and features common to all the constitution types.

Study of a vocal feature selection method and vocal properties for discriminating four constitution types.

The voice has been used to classify the four constitution types, and to recognize a subject's health condition by extracting meaningful physical quantities, in traditional Korean medicine. In this paper, we propose a method of selecting the reliable variables from various voice features, such as frequency derivative features, frequency band ratios, and intensity, from vowels and a sentence. Further, we suggest a process to extract independent variables by eliminating explanatory variables and reducing their correlation and remove outlying data to enable reliable discriminant analysis. Moreover, the suitable division of data for analysis, according to the gender and age of subjects, is discussed. Finally, the vocal features are applied to a discriminant analysis to classify each constitution type. This method of voice classification can be widely used in the u-Healthcare system of personalized medicine and for improving diagnostic accuracy.

Review on the current trends in tongue diagnosis systems.

Tongue diagnosis is an essential process to noninvasively assess the condition of a patient's internal organs in traditional medicine. To obtain quantitative and objective diagnostic results, image acquisition and analysis devices called tongue diagnosis systems (TDSs) are required. These systems consist of hardware including cameras, light sources, and a ColorChecker, and software for color correction, segmentation of tongue region, and tongue classification. To improve the performance of TDSs, various types TDSs have been developed. Hyperspectral imaging TDSs have been suggested to acquire more information than a two-dimensional (2D) image with visible light waves, as it allows collection of data from multiple bands. Three-dimensional (3D) imaging TDSs have been suggested to provide 3D geometry. In the near future, mobile devices like the smart phone will offer applications for assessment of health condition using tongue images. Various technologies for the TDS have respective unique advantages and specificities according to the application and diagnostic environment, but this variation may cause inconsistent diagnoses in practical clinical applications. In this manuscript, we reviewed the current trends in TDSs for the standardization of systems. In conclusion, the standardization of TDSs can supply the general public and oriental medical doctors with convenient, prompt, and accurate information with diagnostic results for assessing the health condition.

Novel diagnostic algorithm for the floating and sunken pulse qualities and its clinical test.

We propose a novel classification algorithm for the floating pulse and the sunken pulse using a newly defined coefficient (C(fs)). To examine the validity of the proposed algorithm, we carried out a clinical test in which 12 oriental medical doctors made pairwise diagnoses on the pulses of volunteering subjects. 169 subjects were simultaneously diagnosed by paired doctors, and the diagnoses in 121 subjects were concordant, yielding an accuracy of 72% and a Matthews correlation coefficient of 0.42, which indicates reasonable agreement between doctors. Two sample T-tests showed that subjects in the sunken pulse group had significantly higher BMI and C(fs) (P < .05) than those in the floating pulse group. The pulse classification by the algorithm converged with the diagnoses of paired doctors with an accuracy up to 69%. With these results, we confirm the validity of the novel classification algorithm for the floating and sunken pulses.

Feature selection from a facial image for distinction of sasang constitution.

Recently, oriental medicine has received attention for providing personalized medicine through consideration of the unique nature and constitution of individual patients. With the eventual goal of globalization, the current trend in oriental medicine research is the standardization by adopting western scientific methods, which could represent a scientific revolution. The purpose of this study is to establish methods for finding statistically significant features in a facial image with respect to distinguishing constitution and to show the meaning of those features. From facial photo images, facial elements are analyzed in terms of the distance, angle and the distance ratios, for which there are 1225, 61 250 and 749 700 features, respectively. Due to the very large number of facial features, it is quite difficult to determine truly meaningful features. We suggest a process for the efficient analysis of facial features including the removal of outliers, control for missing data to guarantee data confidence and calculation of statistical significance by applying ANOVA. We show the statistical properties of selected features according to different constitutions using the nine distances, 10 angles and 10 rates of distance features that are finally established. Additionally, the Sasang constitutional meaning of the selected features is shown here.