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ObjectiveThe purpose of this study was to predict the four cold–heat patterns in patients who have the subjective symptoms of the cold–heat pattern described in the International Classification of Diseases Traditional Medicine Conditions – Module 1 by applying a machine learning algorithm.MethodsSubjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern.ResultsWe included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold–heat pattern.ConclusionWe developed a prediction model on cold–heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold–heat pattern diagnosis by the physician.

BackgroundResearch on early psychosis has begun to identify psychiatric characteristics of the prodromal period of schizophrenia; however, subclinical characteristics of children in non-psychiatric fields have not been fully investigated. In our previous study, we developed the Child Psychosis-risk Screening System (CPSS).ObjectiveIn the present cross-sectional study, we attempted to identify the risk of developing psychosis in pediatric (n = 216) and psychiatric outpatients (n = 120), aged 6– 18 years, with the CPSS.MethodsAn analysis of variance of CPSS risk was performed in six diagnostic categories to examine specificity for each diagnosis. Receiver operating characteristic (ROC) curve analysis was conducted using the onset of schizophrenia spectrum as the outcome, and the discriminatory power and cut off values of the CPSS were determined. Logistic regression analysis was performed using clinical data to identify factors associated with the risk group (those at high risk of developing psychosis in the future) identified using the CPSS.ResultsThere were significant differences in risk variance among diagnostic categories (p

AimsThe excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD.Materials and methods99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors.ResultsFast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively).ConclusionThe current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD.

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom’s relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan–Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03–3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference −0.13, 95% CI −0.27–0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients.Clinical Trial Registration:https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020]

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.

Olfactory dysfunction in the post COVID-19 condition reported worldwide are refractory for some patients. For this reason, appropriate treatment is desired. In this article, we describe two cases of olfactory dysfunction in the post COVID-19 condition that was improved by traditional acupuncture treatment. By using the Yingxiang point (LI20), which is said to improve the sense of smell since ancient times, acupuncture treatment was performed 1–2 times a week in two patients about 6 and 7 months after the diagnosis of COVID-19. Acupuncture needles with a body length of 30 mm and a body diameter of 0.16 mm were inserted about 10 mm deep into the skin. We stimulated LI20 of the right and left sides until the patients felt the de qi sensation (acupuncture resonance), and left needles in the points for about 15 min. Immediately after the acupuncture treatment, the symptoms of olfactory dysfunction were alleviated, and the improvement in olfactory dysfunction lasted for 2–4 days. As the number of acupuncture treatments increased, the time until the flareup of olfactory dysfunction was prolonged, and the symptoms tended to decrease. In our experience, the acupuncture treatment was effective in a short period for treating residual olfactory dysfunction of the post COVID-19 condition, suggesting that acupuncture may serve as an adjunct to modern medical treatment, and it may also be a new option for patients who are resistant to Western medical treatment or unable to continue treatment because of side effects. In conclusion, acupuncture may be a new option for patients who are resistant to modern medical treatment or who are unable to continue treatment because of side effects.

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient’s physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula–pattern pairings. The present study aims to develop such pairings.Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models.Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (大柴胡湯), Dai-joki-To (大承気湯), Shigyaku-San (四逆散), Saiko-ka-ryukotsu-borei-To (柴胡加竜骨牡蛎湯), Keishi-bukuryo-Gan (桂枝茯苓丸), Hachimi-jio-Gan (八味地黄丸), Hange-shashin-To (半夏瀉心湯), Sho-saiko-To (小柴胡湯), Hochu-ekki-To (補中益気湯), Sho-kenchu-To (小建中湯), Toki-shakuyaku-San (当帰芍薬散), Ninjin-To (人参湯), and Dai-kenchu-To (大建中湯).Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education.

AimIn tongue diagnosis, a dark purple tongue and enlarged sublingual vein are important findings of Oketsu (blood stasis). However, the association between the tongue color and the sublingual vein has not been reported. This study investigated the association between the tongue color values and the sublingual vein width using tongue image analyzing system (TIAS) for the objective assessment of blood stasis.MethodsA total of 38 patients (age 68.7 ± 11.3 years, 14 men and 24 women) who visited the Department of Kampo Medicine at Chiba University Hospital were included. Physical findings, blood test results, blood stasis score from medical records, and tongue images obtained with TIAS were analyzed. The patients were classified into two groups: patients with a sublingual vein width of ≤2.5 mm (20 patients) and those with a width of >2.5 mm (18 patients). The physical findings and the blood test results of the two groups were analyzed by Wilcoxon's rank-sum test or χ2-test, whereas logistic regression analysis was used to determine the association between the tongue color values and sublingual vein width. Receiver operating characteristic (ROC) analysis was used to differentiate blood stasis.ResultsThe color values significantly related to the sublingual vein width (mm) were the P1-L* and P4-L* (darkness of the tongue edge and tongue apex) and the P1-b* and P2-b* (blueness of the tongue edge and tongue posterior). The area under the curve was greater for the combination of the tongue color values and the sublingual vein width than that for either of them.ConclusionThis study demonstrated an objective evaluation of blood stasis in the tongue of patients with dark-blue discoloration and an enlarged sublingual vein. In addition, the combination of the tongue color and the sublingual vein is expected to facilitate a more reliable diagnosis of blood stasis.

Praising behavior is considered to be verbal and nonverbal behaviors that expresses praise the behavior and character of the target. However, how one should use verbal and nonverbal behaviors to successfully praise a target has not been clarified. Therefore, we focus on attempts to analyze praising behavior in Japanese dialogue using verbal and nonverbal behaviors. In this study, we attempted to analyze the relationship between praising skills and human behaviors in Japanese dialogue by focusing on voice, head, and face behaviors. First, we created a new dialogue corpus in Japanese containing voice, head, and face behaviors from individuals giving praise (praiser) and receiving praise (receiver), as well as the degree of success of praising (praising score). Second, we developed machine learning models that uses features related to voice, head, and face behaviors to estimate praising skills to clarify which features of the praiser and receiver are important for estimating praising skills. Evaluation resulte showed that some audio features of the praiser are particularly important for estimation of praising skills. Our analysis results demonstrated the importance of features related to the zero-crossing rate, MFCCs of the praiser. Analyzing the features of high importance revealed that the praiser should praise with specific words that mean amazing or great in Japanese and the voice quality of the praiser is considered to be important for praising successfully.

Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model’s pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.

Coronavirus disease 2019 (COVID-19) spread to Japan in 2020, where the number of infected patients exceeded 250,000 and COVID-related deaths exceeded 3,500 in one year. Basic guidelines for infection control were implemented in Japan, and research and development of effective drugs and vaccines were promoted. This included considering Kampo medicine, which has a long history of treating recurring emerging viral infections. Considering the characteristics of the disease (inflammation of the upper and lower respiratory tract as well as potential neural damage and vasculitis), Kampo medicine could be considered as a treatment strategy due to its antiviral and anti-inflammatory effects induced by multiple active substances that could aid in disease prevention and recovery. In this study, case reports on the management of COVID-19 with Kampo medicine, which were published until March 31, 2021, were reviewed. The search strategy involved the use of Medline and hand-searching. Twenty two patients were treated using Kampo medicines with or without Western medicine, based on individual conditions. On the other hand, the effects of Kampo medicines as a potential preventive treatment (pre-infection), active treatment (especially in the acute and subacute stage), or treatment of sequelae to aid recovery (after infection) in the different stages of COVID-19 are being studied as research projects in the Japan Society for Oriental Medicine (JSOM). JSOM has also organized a pioneering project of clinical trials for COVID-19, some of which are now in progress.

Liquorice is usually used as crude drug in traditional Japanese Kampo medicine and traditional Chinese medicine. Liquorice-containing glycyrrhizin (GL) can cause pseudohyperaldosteronism as a side effect. Previously, we identified 18β-glycyrrhetyl-3-O-sulfate (3) as a GL metabolite in Eisai hyperbilirubinuria rats (EHBRs) with the dysfunction of multidrug resistance-related protein (Mrp2). We speculated that 3 was associated with the onset of liquorice-induced pseudohyperaldosteronism, because it was mainly detected in serum of patients with suspected to have this condition. However, it is predicted that other metabolites might exist in the urine of EHBRs orally treated with glycyrrhetinic acid (GA). We explored other metabolites in the urine of EHBRs, and investigated the pharmacokinetic profiles of the new metabolite in EHBRs and normal Sprague-Dawley rats. We further analyzed the serum concentrations of the new metabolite in the patients of pseudohyperaldosteronism. Finally, we developed the analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA). We isolated a new GL metabolite, 18β-glycyrrhetyl-3-O-sulfate-30-O-glucuronide (4). Compound 4 significantly inhibited rat type-2 11β-hydroxysteroid dehydrogenase (11β-HSD2) and was a substrate of both organic anion transporter (OAT) 1 and OAT3. Compound 4 was also detected in the serum of patients with suspected pseudohyperaldosteronism at an approximately 10-fold lower concentrations than 3, and these concentrations were positively correlated. Compound 4 showed a lower serum concentration and weaker inhibitory titer on 11β-HSD2 than 3. We developed an enzyme-linked immunosorbent assay system using an anti-18β-glycyrrhetyl-3-O-glucuronide (3MGA) monoclonal antibody to measure the serum concentration of 3 to facilitate the measurement of biomarkers to predict the onset of pseudohyperaldosteronism. Although we found 4 as the secondary candidate causative agent, 3 could be the main potent preventive biomarker of liquorice-induced pseudohyperaldosteronism. Compound 3 was detected in serum at a higher concentration than GA and 4, implying that 3 may be a pharmacologically active ingredient mediating not only the development of pseudohyperaldosteronism but anti-inflammatory effects in humans administered GL or other liquorice-containing preparations.

The effect of near-fault ground displacement is a significant factor when structures straddle a fault, because the fault produces both static step-like deformations and dynamic pulse-like ground motions. It has been observed that the static displacements measured up to 10 m and strong ground motion velocity pulses exceed 100 cm/s. As there is no concrete method for the seismic design of near-fault structures based on earthquake-induced fault displacement, the numerical simulation of near-fault ground motions is of great significance. In this paper, we describe a hybrid method combining stochastic and theoretical Green’s functions for synthesizing near-fault ground motions. Our approach considers the complete waveforms (far-, intermediate-, and near-field terms) of both the dynamic and static terms. To demonstrate the hybrid method, two simple examples of strike-slip and dip-slip fault models are simulated. The results exhibited dynamic displacement with the fling-step of near-fault movement. Furthermore, the 1999 Chi-Chi earthquake in Taiwan is also simulated, and the results showed good agreement with the observed recordings. Thus, the proposed method is a useful tool for evaluating near-fault ground motions for designing bridges and other structures.