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Aim: We present the study protocol of a multicenter, retrospective observational study that aims to investigate the efficacy of the actual treatment (the efficacy of conventional and Kampo medicines) of patients with mild to moderate or suspected coronavirus disease (COVID-19) Methods: This study is designed as a multicenter, retrospective observational study Outpatients and inpatients will be recruited from Japanese hospitals The inclusion criteria are as follows: having or suspected to have COVID-19, mild to moderate COVID-19, symptomatic, ≥20 years of age, male or female, able to communicate in Japanese, and treated with conventional and Kampo medicine The exclusion criteria are: unable to provide informed consent due to dementia, psychosis, or psychiatric symptoms, severe COVID-19, or determined unsuitable for this study The sample size is set at 1000, as this number of people can be treated at the collaborating medical institutions during the study period Results: The main outcome is the number of days without fever, with a body temperature of less than 37°C The secondary outcome is set at common cold-like symptoms other than fever (fatigue, cough, shortness of breath, sputum, diarrhea) and severity of illness and hospitalization up to 14 days after the visit Trial registration: The trial was registered in the University Hospital Medical Information Network (Reservation No UMIN000041301) on August 4, 2020 Conclusion: Our study will explore the contribution of conventional and Kampo medicine in the treatment of patients with mild and moderate COVID-19

In this report, we present two cases in which benzodiazepines (BZDs) were able to be successfully reduced or discontinued by treatment with traditional Japanese herbal medicine (Kampo medicine), including Hangekobokuto (HKT). These two patients with long‐term use of BZDs due to mental disorders suffered epigastric symptoms. After starting Kampo therapy including HKT, their epigastric symptoms were improved and they were able to reduce or discontinue the use of BZDs. This suggests that HKT is a potentially promising substitutive pharmacotherapy for patients with long‐term use of BZDs. HKT should be considered as a treatment for patients with mental disorders who have taken BZDs for a long time and suffer from medically unexplained epigastric symptoms., In this report, we present two cases in which benzodiazepines were able to be successfully reduced or discontinued by treatment with traditional Japanese herbal medicine (Kampo medicine), including Hangekoubokutou (HKT). HKT is a potentially promising substitutive pharmacotherapy for patients with long‐term use of benzodiazepines.

In this report, we present a case in which long‐term swelling and pain because of an ankle sprain were successfully treated with the traditional Japanese herbal (Kampo) medicine Jidabokuippo. Jidabokuippo was created in Japan and has been used to treat swelling and pain associated with trauma. A 44‐year‐old woman sprained her right ankle and received the standard treatments including icing and immobilization for three weeks. However, the swelling, redness, and pain of her ankle continued for two months after the treatments. After initiating Jidabokuippo, her pain and swelling were promptly improved. This suggests that Jidabokuippo is a potentially promising pharmacotherapy for patients with ankle sprain which has not recovered smoothly. It is said that Jidabokuippo can be prescribed simply referring to pain and swelling of the affected areas; therefore, it should be considered as a treatment for trauma patients with long‐term swelling and pain., Jidabokuippo could be a useful medication for patients with ankle sprain which has not recovered quickly. Jidabokuippo can be prescribed simply referring to swelling and pain of the affected areas . his information may be valuable for primary care physicians who have to treat non‐internal medicine‐related health problems.

Objective The purpose of the present study was to compare important patient questionnaire items by creating a random forest model for predicting deficiency-excess pattern diagnosis in six Kampo specialty clinics. Design A multi-centre prospective observational study. Setting Participants who visited six Kampo specialty clinics in Japan from 2012 to 2015. Main outcome measure Deficiency-excess pattern diagnosis made by board-certified Kampo experts. Methods To predict the deficiency-excess pattern diagnosis by Kampo experts, we used 153 items as independent variables, namely, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We extracted the 30 most important items in each clinic’s random forest model and selected items that were common among the clinics. We integrated participating clinics’ data to construct a prediction model in the same manner. We calculated the discriminant ratio using this prediction model for the total six clinics’ data and each clinic’s independent data. Results Fifteen items were commonly listed in top 30 items in each random forest model. The discriminant ratio of the total six clinics’ data was 82.3%; moreover, with the exception of one clinic, the independent discriminant ratio of each clinic was approximately 80% each. Conclusions We identified common important items in diagnosing a deficiency-excess pattern among six Japanese Kampo clinics. We constructed the integrated prediction model of deficiency-excess pattern.

Objective The purpose of this study was to extract important patient questionnaire items by creating random forest models for predicting pattern diagnosis considering an interaction between deficiency-excess and cold-heat patterns. Design A multi-centre prospective observational study. Setting Participants visiting six Kampo speciality clinics in Japan from 2012 to 2015. Main outcome measure Deficiency–excess pattern diagnosis made by board-certified Kampo experts. Methods We used 153 items as independent variables including, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We sampled training data with an equal number of the different patterns from a 2 × 2 factorial combination of deficiency–excess and cold–heat patterns. We constructed the prediction models of deficiency–excess and cold–heat patterns using the random forest algorithm, extracted the top 10 essential items, and calculated the discriminant ratio using this prediction model. Results BMI and blood pressure, and subjective symptoms of cold or heat sensations were the most important items in the prediction models of deficiency–excess pattern and of cold–heat patterns, respectively. The discriminant ratio was not inferior compared with the result ignoring the interaction between the diagnoses. Conclusions We revised deficiency–excess and cold–heat pattern prediction models, based on balanced training sample data obtained from six Kampo speciality clinics in Japan. The revised important items for diagnosing a deficiency–excess pattern and cold–heat pattern were compatible with the definition in the 11th version of international classification of diseases.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

The joint international symposium of the 22nd Hiroshima Cancer Seminar and the 4th Japanese Association for RNA Interference focused on a pivotal role of microRNAs in carcinogenesis, progression and therapy of human cancer. Mammalian immune regulator MCPIP1 (Zc3h12a) RNase acts as a novel suppressor of microRNA activity and biogenesis, suggesting the involvement of MCPIP1 in the alteration of microRNA biogenesis in tumorigenesis. Gene set enrichment analysis and functional assignment of microRNAs via enrichment analysis enable the prediction of microRNA activities from mRNA expression data by combining rank-based enrichment analysis and weighted evaluation of microRNA-mRNA interactions. MiR-124 and miR-203 function as tumor-suppressor microRNAs silenced by DNA methylation in hepatocellular carcinoma. Stella-induced DNA hypomethylation would confer the pathogenic function of DNA hypomethylation in cancer. Senescence-associated microRNA, miR-22, suppresses tumor growth and metastasis in vivo in a murine breast cancer model, and exosomal senescence-associated microRNA may affect the tumor microenvironment. The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics. MiR-1 and miR-133a cluster may function as tumor suppressors regulating novel pathways in human cancers. The down-regulation of miR-148a is implicated in invasion of gastric cancer, while high miR-21 expression in colorectal cancer is associated with poor survival. Neutral sphingomyelinase 2 regulates exosomal microRNA secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis; in particular, the exosomal miR-210 secretion by neutral sphingomyelinase 2 confers the formation of the tumor vessel network.

Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049–0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual patients. This paper was done to assess the risk of hepatotoxicity by the coumarin contained in Kampo medicines and to clarify whether or not the Kampo preparations in general use that contain cinnamon bark may be safely used in clinical practice.

The 21st Hiroshima Cancer Seminar focused on recent progress of carcinogenesis, progression and management of upper gastrointestinal cancers. β-Catenin and p120 mediate peroxisome proliferator-activated receptor δ-dependent proliferation induced by Helicobacter pylori in gastric epithelia. Helicobacter pylori CagA plays an important role in stomach carcinogenesis via altered signal transduction and cell polarity by interactions with several host proteins. Inflammation caused by H. pylori infection is responsible for inducing aberrant DNA methylation. The gastric gland mucin-specific αGlcNAc plays dual roles in preventing gastric cancer, inhibition of H. pylori infection and suppression of tumor-promoting inflammation. Information obtained from transcriptome dissection greatly contributes to understanding the molecular character of each mucin phenotype of gastric cancer. The standardized biomarkers will serve as good predictive and prognostic markers for gastric cancer. A microRNA expression profile may be useful for the diagnosis of gastric cancer. Bone marrow-derived mesenchymal stem cells may provide an advantageous microenvironment for re-acquisition of stemness of gastric cancer cells. Recent progress in molecular biology research has enabled the clinical development of molecular targeting agents for gastric cancer, such as trastuzumab. The target molecule-based inhibition of the stromal reaction in the microenvironment may hold promise as an effective anti-tumor therapy. Since robotic surgery is feasible and safe, and provides adequate and precise lymph node dissection, it may be one of the good options for gastric cancer in the near future.