1.Analysis of Related Factors that Make Daikenchuto Useful for Constipation During Pregnancy
Takeshi NAKAYAMA ; Aki MUKAI ; Kyoko SUZUKI ; Shuhei SO ; Nao MURABAYASHI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Hiroaki ITOH
Kampo Medicine 2022;73(1):1-7
		                        		
		                        			
		                        			The purpose of this study is to clarify factors related to the effect of daikenchuto on constipation during pregnancy. The subjects were 21 patients who had constipation during pregnancy and received 15 g/day of daikenchuto. Based on the constipation score that was created independently, the score values before administration, 2 weeks and 4 weeks after administration were retrospectively investigated. Furthermore, from the outcome of the oral status at 4 weeks, we divided the patients into 2 groups (12 in the improvement group and 11 in the non-improvement group), and attempted to extract factors that were considered to be related to efficacy. The total constipation score decreased significantly before and after administration of daikenchuto, and the concomitant symptoms of constipation scores were low, especially such as abdominal distension and abdominal pain. A comparison of the backgrounds of the improved group and the non-improved group revealed that the proportion of the patients with a history of surgery (laparotomy or laparoscopic surgery) was significantly higher in the improvement group. In addition, there were no particular problems with the pregnancy and delivery course of the 23 patients. Daikenchuto was considered to be highly effective against constipation during pregnancy, especially in pregnant women with a history of surgery.
		                        		
		                        		
		                        		
		                        	
2.Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles
Takuro HIRANO ; Eri ARAI ; Mao FUJIMOTO ; Yuji NAKAYAMA ; Ying TIAN ; Nanako ITO ; Takeshi MAKABE ; Wataru YAMAGAMI ; Nobuyuki SUSUMU ; Daisuke AOKI ; Yae KANAI
Journal of Gynecologic Oncology 2022;33(6):e74-
		                        		
		                        			 Objective:
		                        			The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. 
		                        		
		                        			Methods:
		                        			Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. 
		                        		
		                        			Results:
		                        			Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. 
		                        		
		                        			Conclusions
		                        			DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used. 
		                        		
		                        		
		                        		
		                        	
3.Significance of Combined Use of Kamishoyosan and Tokishakuyakusan for General Infertility Treatment
Takeshi NAKAYAMA ; Fumiko TAWARA ; Nao MURABAYASHI ; Shuhei SO ; Wakasa YAMAGUCHI ; Naomi MIYANO ; Kensuke UETA ; Kyoko SUZUKI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Aki MUKAI ; Naoaki TAMURA ; Hiroaki ITOH ; Naohiro KANAYAMA
Kampo Medicine 2021;72(4):361-367
		                        		
		                        			
		                        			We aimed to clarify the significance of using Kampo therapy centered on kamishoyosan and tokishakuyakusan together with general infertility treatment. The subjects were 41 women who visited a Kampo outpatient clinic for infertility and received general infertility treatment with Kampo therapy (Kampo group). The control group was 781 women who received only general infertility treatment at the same time (non-Kampo group). In comparing both groups, we conducted a retrospective survey on the pregnancy rate by cycle and the pregnancy rate by prescription. The pregnancy rate in the first cycle was 24.4% in the Kampo group and 8.5% in the non-Kampo group, and the pregnancy rate was higher in the Kampo group (P = 0.003). There was no difference in pregnancy rates after the second cycle. The pregnancy rate by prescription was 26.7% for kamishoyosan, 22.2% for tokishakuyakusan, and 8.5% for the non-Kampo group. In the comparison between the first cycle pregnant group and the non-pregnant group, the qi counter flow score was clearly higher in the first cycle pregnant group (P = 0.012). It is suggested that combined use of Kampo therapy including kamishoyosan and tokishakuyakusan may be effective from an early stage. Meanwhile, if pregnancy does not occur even after the combined use of Kamp therapy, it would be an opportunity to consider stepping up as Western medical therapy.
		                        		
		                        		
		                        		
		                        	
4.The Physicians’ Barriers to Practice of Advance Care Planning:A Single Facility Questionnaire Survey
Tomohiro NAKAYAMA ; Takeshi YOSHIDA ; Masanori MORI
Palliative Care Research 2021;16(1):19-25
		                        		
		                        			
		                        			Background: Although practicing advanced care planning (ACP) has recently been recommended, little is known about physicians’ practice of ACP, and barriers to ACP in Japan. We aimed to clarify the proportion of physicians practicing ACP and explore barriers to ACP. Methods: We conducted a cross-sectional survey among physicians at a tertiary hospital (934 beds) in 2019, and asked them about their practice and awareness of ACP as well as beliefs regarding end-of-life discussions. A multivariate logistic regression analysis was conducted to explore barriers to their practice of ACP. Results: In total, 90 of 186 physicians responded (response rate, 48%). Forty-two (46%; 95% confidence interval=37-57%) reported that they practiced ACP. In multivariate analysis, determinants of “not” practicing ACP included the lack of awareness of ACP and physicians’ greater beliefs regarding the lack of resources as well as the lack of time and perception of burden. Conclusion: Even at the tertiary hospital, only less than a half of physicians practiced ACP, and the lack of their awareness of ACP and various beliefs served as barriers to their practice. Initiatives to raise awareness of ACP and optimize the management to ensure sufficient time and resources for physicians may be promising to promote ACP.
		                        		
		                        		
		                        		
		                        	
5.A Case of Secondary Amenorrhea with Polycystic Ovary Syndrome Successfully Treated with Shokenchuto
Takeshi NAKAYAMA ; Aki MUKAI ; Kyoko SUZUKI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Hiroaki ITOH
Kampo Medicine 2021;72(2):177-181
		                        		
		                        			
		                        			Here, we report a case of adolescent woman with secondary amenorrhea complicated with polycystic ovary syndrome, which had a normal menstrual period after prescribed shokenchuto under the therapy based on Kampo diagnosis. The case is 14-year-old woman, who had already hormonal therapy due to the secondary amenorrhea, and was difficult to treat because of edema and weight gain. Secondary amenorrhea, multiple cysts in the ovary, and hypertestosteroneemia were confirmed, and the patient was diagnosed with polycystic ovary syndrome. Abdominal pattern was weak and the abnormalities of the abdominal strength were prominent. Therefore, we administered her shokenchuto. After two weeks, menstruation began, and thereafter the menstruation had progressed without any irregularities. Blood examination also showed normal testosterone level. It was suggested that it would be important to focus on the preparation for digestive function and to treat the secondary amenorrhea of adolescent women.
		                        		
		                        		
		                        		
		                        	
6.Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.
Keisuke HIOKI ; Yuki ITO ; Naoko OYA ; Shoji F NAKAYAMA ; Tomohiko ISOBE ; Takeshi EBARA ; Kanemitsu SHIBATA ; Naomi NISHIKAWA ; Kunihiko NAKAI ; Tomota KAMIDA ; Jun UEYAMA ; Mayumi SUGIURA-OGASAWARA ; Michihiro KAMIJIMA
Environmental Health and Preventive Medicine 2019;24(1):7-7
		                        		
		                        			BACKGROUND:
		                        			Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan.
		                        		
		                        			METHODS:
		                        			Urine samples were collected from 62 non-smoking pregnant women (12-22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses.
		                        		
		                        			RESULTS:
		                        			For all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points.
		                        		
		                        			CONCLUSION
		                        			This study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Chromatography, Liquid
		                        			;
		                        		
		                        			Creatinine
		                        			;
		                        		
		                        			urine
		                        			;
		                        		
		                        			Environmental Exposure
		                        			;
		                        		
		                        			analysis
		                        			;
		                        		
		                        			Environmental Monitoring
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Environmental Pollutants
		                        			;
		                        		
		                        			urine
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Japan
		                        			;
		                        		
		                        			Mass Spectrometry
		                        			;
		                        		
		                        			Organophosphates
		                        			;
		                        		
		                        			urine
		                        			;
		                        		
		                        			Pesticides
		                        			;
		                        		
		                        			urine
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Pregnant Women
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
7.ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture system.
Masaharu NOI ; Ken-Ichi MUKAISHO ; Saori YOSHIDA ; Shoko MURAKAMI ; Shinya KOSHINUMA ; Takeshi ADACHI ; Yoshisato MACHIDA ; Masashi YAMORI ; Takahisa NAKAYAMA ; Gaku YAMAMOTO ; Hiroyuki SUGIHARA
International Journal of Oral Science 2018;10(4):30-30
		                        		
		                        			
		                        			To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase (ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbed with a structure resembling the loose connective tissue morphology in a novel 3D culture system. We confirmed that the 3D system using Cellbed accurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3D-cultured tongue cancer cell lines than in 2D cultures. Typically, under conventional 2D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells. However, in the 3D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3D culture systems using Cellbed™ are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.
		                        		
		                        		
		                        		
		                        			Carcinoma in Situ
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Carcinoma, Squamous Cell
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Cell Culture Techniques
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Cell Movement
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Cytoskeletal Proteins
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Extracellular Signal-Regulated MAP Kinases
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Neoplasm Invasiveness
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Phosphorylation
		                        			;
		                        		
		                        			Podosomes
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Silicon Dioxide
		                        			;
		                        		
		                        			Tongue Neoplasms
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Tumor Cells, Cultured
		                        			
		                        		
		                        	
8.Brain information processing of high performance football players during decision Making -a study of event-related potentials and electromyography reaction time-
Takahiro MATSUTAKE ; Takayuki NATSUHARA ; Masaaki KOIDO ; Kensuke SUZUKI ; Yusuke TABEI ; Masao NAKAYAMA ; Takeshi ASAI
Japanese Journal of Physical Fitness and Sports Medicine 2018;67(1):107-123
		                        		
		                        			
		                        			In this study, observing football players under simulated playing conditions to measure event-related potentials (ERPs, i.e. P300), electromyography reaction time (EMG-RT), and reaction time (RT), we investigated neural correlates of information processing during selective reaction challenges. A high performance group included 13 collegiate football players who had previously won the All Japan University Championships. A low performance group included 13 collegiate football players who never competed at the national level or played in prefectural or regional competitions. We conducted a 4 vs. 2 ball possession task (i.e. a Go/NoGo task) under simulated playing conditions that required situational assessment. Our results showed that the high-performance group had a significantly higher correct response rate than did the low-performance group in 4 vs. 2 ball possession tasks. Moreover, the EMG-RT and RT of the high-performance group were significantly shorter than that of the low-performance group. Furthermore, the P100 and P300 latencies of the high-performance group was significantly shorter than those of the low-performance group. These findings indicated that high-performance football players could perform the task-relevant stages of information processing (such as visual information processing, stimulus evaluation, and motor response output) in a short time. There was no correlation between EMG-RT and P100 (Go, NoGo stimulation), indicating that initial visual information processing did not contribute to the execution of the final motor response. There was no correlation between EMG-RT and Go P300 latency, whereas a significant correlation with NoGo P300 latency was shown. This suggested that the stimulus evaluation system by NoGo stimuli (response inhibition) is strongly involved in the final motor output reaction.
		                        		
		                        		
		                        		
		                        	
9.Rikkunshito Improves the Nausea, Vomiting and Anorexia Induced with the Hyperemesis Gravidarum
Takeshi NAKAYAMA ; Tomijiro NISHIHARA ; Serino FUKADA
Kampo Medicine 2017;68(2):105-110
The aim of this study is to retrospectively examine the efficacy of rikkunshito in comparison with shohangekabukuryoto and metoclopramide, administered to patients with hyperemesis gravidarum, using with the emesis index (EI) proposed by Kitagawa, et al. Total EI score for all groups was decreased with the passage of time, although EI in the rikkunshito group at day 7 was significantly lower than that of the other shohangekabukuryoto and metoclopramide groups. All nausea, vomiting and anorexia, scores were significantly lower in the rikkunshito group. These results suggest that rikkunshito is as effective in hyperemesis gravidarum as shohangekabukuryoto and metoclopramide are, and more effective for the gastrointestinal symptoms of nausea and vomiting, anorexia. The group in which rikkunshito was ineffective tended have a higher qi counterflow score, thus treatment modifications with qi circulating medicine would be required in accordance with sho patterns.
10.Study on Six Cases of Infertile Women with Clomiphene-Resistant Polycystic Ovary Syndrome Successfully Treated with Concomitant Saireito Therapy
Kampo Medicine 2015;66(2):83-88
		                        		
		                        			
		                        			Polycystic ovary syndrome (PCOS) occurs in 5 to 8% of females of reproductive age and is one of the leading causes of menstrual abnormalities and infertility. The treatment of PCOS varies, depending on the patient's age and background, particularly on the presence/absence of a desire to have children. In those desiring to have children, clomiphene therapy is the first-line treatment for PCOS. However, the anti-estrogen action of clomiphene may lead to a thinning of the endometrium and decreased cervical mucus production, while some patients show a poor response to the agent. In this study, saireito was administered to clomiphene-resistant PCOS patients, and the ovulation cycle improved in 6. Effective cases of saireito tended to have higher oketsu (blood stagnation) and suitai (water stagnation) statescores before treatment, also serum LH levels and LH/FSH ratios were lower due to the concurrent saireito medication. Furthermore, these effective cases had lower levels of serum testosterone than the non-effective and clomiphene-effective cases. This clinical report suggests the appropriateness of performing this therapy in accordance with sho (oriental patterns or symptoms), before second-line treatments such as gonadotropin therapy or laparoscopic surgery.
		                        		
		                        		
		                        		
		                        	
            

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