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Open Journal of Genetics 2012年第1期2卷 62-69页

作者： masanori Ito Department of Pharmacology School of Medicine Faculty of Medicine Toho University 5-21-16 Omori-Nishi Otaku Tokyo 143-8540 Japan

Silencing of gene expression by RNA interference (RNAi) has become a widely used tool. For the study of mammalian gene function expression vectors for short hairpin RNA (shRNA) were developed. However the standard methods of shRNA transgenic (Tg) mice production have not been established. Sry (sex-determining region on the Y chromosome) is a mammalian sex-determining gene on the Y chromosome. In mice, the transient expression of Sry in supporting cell precursor cells between 10.5 and 12.5 days post-coitus (dpc) triggers the differentiation of Sertoli cells from granulosa cells. Then high efficiency of Sry gene silencing in Tg mice should induce XY male-to-female sex reversal. An shRNA Tg mouse targeting Sry gene was attempted to be generated by pronuclear microinjection. A low rate (Tg pups/all pups born after microinjection = 2/154 to 7/178) of Tg pups was observed. These Tg mice showed no XY male-to-female sex reversal. The results suggest that exogenous expression of small RNA might exert a negative effect on embryonic development and another approach should be needed for RNAi transgenesis in mice.

关键词： Transgenic Mice Pronuclear Microinjection RNA Interference

Multikinase inhibitor-associated hand-foot skin reaction as a predictor of outcomes in patients with hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2018年第28期24卷 3155-3162页

作者： masanori Ochi Toshiro Kamoshida Atsushi Ohkawara Haruka Ohkawara Nobushige Kakinoki Shinji Hirai Akinori Yanaka Department of Gastroenterology Hitachi General Hospital Hitachi Medical Education and Research Center University of Tsukuba

AIM To investigate the relationship between the onsets of multikinase inhibitor(MKI)-associated hand-foot skin reaction(HFSR) and prognosis under intervention by pharmacists after the introduction of *** We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival(OS) after the initiation of *** The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this *** Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.

关键词： Hepatocellular carcinoma Surrogate marker Multikinase inhibitor-associated hand-foot skin reaction Sorafenib Intervention by pharmacists

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

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World Journal of Gastroenterology 2020年第33期26卷 4960-4971页

作者： Chisato Saeki Mitsuru Saito Tsunekazu Oikawa masanori Nakano Yuichi Torisu Masayuki Saruta Akihito Tsubota Division of Gastroenterology and Hepatology Department of Internal MedicineThe Jikei University School of MedicineTokyo 1058461Japan Department of Orthopaedic Surgery The Jikei University School of MedicineTokyo 1058461Japan Core Research Facilities Research Center for Medical ScienceThe Jikei University School of MedicineTokyo 1058461Japan

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)*** has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general ***,there are few reports evaluating the efficacy of denosumab in CLD *** To investigated the effects and safety of denosumab in CLD patients with *** Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 *** study period for evaluating efficacy and safety was 12 *** from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab *** turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present *** median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,*** significantly improved BMD,regardless of sex,patient age,and presence of liver *** tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient *** Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective

关键词： Chronic liver disease Denosumab Osteoporosis Bone mineral density Bone turnover Bone quality

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Ⅳ期胃癌转化治疗

Science Bulletin 2023年第7期68卷 653-656页

作者：胡灿 masanori Terashima 程向东 Department of Gastric Surgery Zhejiang Cancer HospitalInstitutes of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer Zhejiang Cancer HospitalHangzhou 310022China Division of Gastric Surgery Shizuoka Cancer CenterShizuoka 411-8777Japan

Gastric cancer(GC)is one of the most common malignant tumors and represents the fourth most common cause of cancer death *** is the optimal treatment for patients with ***,70%–80%of GC patients are diagnosed at locally advanced stages.A large number of clinical studies have shown that no existing treatment has ideal efficacy against advanced unresectable GC with No.16 lymph nodes or distant organ metastasis,and the median survival time of patients is only approximately 10 *** recent years,conversion therapy has shown great *** approach consists mainly of developing reasonable comprehensive treatment programs,including chemotherapy,radiotherapy,and targeted therapy delivered by a multidisciplinary team(MDT),to convert initially unresectable GC to resectable cancer,thus prolonging patients’survival and improving their quality of ***,we aim to discuss the treatment strategies,challenges and opportunities of conversion therapy for GC,along with our experience in conversion therapy for patients with advanced GC(Fig.1).

关键词： Surgery Gastric treatment

Thermal physiological response to local heating and cooling during sleep

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Frontiers of Architectural Research 2012年第1期1卷 51-57页

作者： Yu Hibino Shuichi Hokoi Katsuaki Yoshida Satoru Takada masanori Nakajima Miho Yamate KVOtO University Japan Kobe University Japan The Kansai Electric Power Co. Inc. Japan

For a healthy and productive life, good steep is essential, which has prompted studies on how comfortable sleep can be achieved. Understanding the relationship between thermal environment and physiological responses such as skin and core temperatures, and psychological responses such as thermal and sleep sensations is necessary to identify the most suitable thermal environment for steep. As an energy-saving and practical method of creating the most appropriate thermal environment for sleep, local heating or cooling is sometimes used, which takes into consideration the differences in local thermal responses. We performed this study to identify the most effective thermal environment for inducing comfortable sleep by identifying the physiological responses during sleep on the basis of sleep experiments conducted under local body heating or cooling conditions. We also used a human thermal model, which can be applied for predicting physiological responses. In the experiments, the feet of the subject were the primary area to be heated or cooled, which was achieved by installing a flexible duct with an outlet placed close to the subject＇s feet and inlet connected to an air conditioner. Differences in the fluctuation of body temperature and sleep stage depended on the airflow direction from the duct to the feet. When air was blown downward towards the feet, body temperature decreased and the subject was able to sleep well. Measured skin and core temperatures were calculated using an improved 27-node human thermal model that was originally developed for use in subjects who are not in steep. Although skin

关键词： Sleep Thermal environ-ment Local air conditioning Physiologicalresponse Human thermal mode[

Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis

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World Journal of Hepatology 2018年第1期10卷 82-87页

作者： Hiroya Iida Masaki Kaibori Kosuke Matsui Morihiko Ishizaki masanori Kon Department of Surgery Kansai Medical University

AIM To provide a simple surrogate marker predictive of liver cirrhosis(LC).METHODS Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using MannWhitney U-test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression *** There were significant differences between the LC group(n = 100) and non-LC group(n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type Ⅳ collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99 m diethylene triamine pentaacetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count(MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78,with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%.CONCLUSION The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

关键词： Mean platelet volume Platelet count Liver cirrhosis Hepatic functional reserve Liver fibrosis

Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

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World Journal of Hepatology 2015年第25期7卷 2590-2596页

作者： Katsuhisa Nakatsuka masanori Atsukawa Masumi Shimizu Hidemi Takahashi Chiaki Kawamoto Division of Gastroenterology and Hepatology Department of Internal MedicineNippon Medical School Microbiology and Immunology Nippon Medical School

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are *** up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 *** of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 *** effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead *** findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected *** an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.

关键词： Ribavirin Forkhead box-P3 T helper 1/2cell balance T-regulatory lymphocytes Inducible costimulator Interleukin-10 Hepatitis C virus infection

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流动加速腐蚀引起的管壁减薄分析及验证

金属学报 2011年第7期47卷 784-789页

作者： masanori Naitoh 陈耀东 Shunsuke Uchida Hidetoshi Okada The Institute of Applied Energy Tokyo 105-0003Japan 中国核电工程有限公司北京100840

针对危害电站安全运行的流动加速腐蚀(FAC)现象,结合专用分析程序包DRAWTHREE的模型和结构.阐明了FAC的发生机理及其决定性因素,提出了用于评估FAC和管壁减薄速率的方法和步骤,并将上述程序分析结果与实验及电厂实际测量数据进行了比较... 详细信息

针对危害电站安全运行的流动加速腐蚀(FAC)现象,结合专用分析程序包DRAWTHREE的模型和结构.阐明了FAC的发生机理及其决定性因素,提出了用于评估FAC和管壁减薄速率的方法和步骤,并将上述程序分析结果与实验及电厂实际测量数据进行了比较,结果吻合较好.最后给出了用于缓解FAC的一些措施.

关键词：流动加速腐蚀管壁减薄电化学双氧化层评价程序DRAWTHREE

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新型排列组合高压缩多载波调制系统

通信学报 2007年第1期28卷 69-74页

作者：侯亚飞 HAMAMURA masanori 张世永复旦大学计算机与信息技术系上海200433 高知工科大学情报信息系

提出一种基于高压缩多载波调制(HC-MCM,high compaction multi-carrier modulation)技术和排列组合正交频分复用(PC-OFDM,parallel combinatory OFDM)技术的新型调制系统,即排列组合高压缩多载波调制(PC/HC-MCM)系统。同PC-OFDM系统相比,PC/HC-MCM能够大幅度提高系统的带宽效率。同时给出了2种PC/HC-MCM系统的仿真性能。PC/HC-MCM系统稍加改造可以应用于不同的多载波系统。

关键词：正交频分复用排列组合正交频分复用带宽效率高压缩多载波调制

Endoscopic findings can predict the efficacy of leukocytapheresis for steroid-naive patients with moderately active ulcerative colitis

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World Journal of Gastroenterology 2008年第34期14卷 5316-5321页

作者： Yasushi Umehara Masatoshi Kudo masanori Kawasaki Division of Gastroenterology and Hepatology Department of Internal Medicine Kinki University School of Medicine

AIM:To investigate the therapeutic usefulness of leukocytapheresis (LCAP; Cellsoba) in steroid-naive patients with moderately active ulcerative colitis (UC). METHODS: Eighteen steroid-naive patients with moderately active UC received one LCAP session every week for fi ve consecutive weeks. RESULTS: The remission rate 8 weeks after the last LCAP session was 61.1% (11/18). All three patients with deep ulcers showed worsening after LCAP. For the remaining 15 patients, who had erosions or geographic ulcers, the average clinical activity index (CAI) score dropped significantly from 9.4 to 3.8 eight weeks after the last LCAP session (t = 4.89, P = 0.001). The average C-reactive protein (CRP) levels before and after LCAP were 1.2 mg/dL and 1.0 mg/dL, respectively. Of the patients with erosions, geographic ulcers, and deep ulcers, 100% (9/9), 33.3% (2/6), and 0% (0/3) were in remission 8 weeks after the last LCAP session, respectively (χ2 = 7.65, P < 0.005). Forty- eight weeks after the last LCAP session, the remission rates for patients with erosions and geographic ulcers were 44.4% (4/9) and 16.7% (1/6), respectively. Only one patient suffered a mild adverse event after LCAP (nausea). CONCLUSION: LCAP is a useful and safe therapyfor steroid-naive UC patients with moderate disease activity. Moreover, the effi cacy of the treatment can be predicted on the basis of endoscopic fi ndings.

关键词： Ulcerative colitis Steroid-naive Leukocytapheresis Efficacy Endoscopic findings