물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가

김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

Ginsenoside Rg1 alleviates A deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice

Han Zhang,Yong Su,Zhenghao Sun,Ming Chen,Yuli Han,Yan Li,Xianan Dong,Shixin Ding,Zhirui Fang,Weiping Li,Weizu Li 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for thetreatment of Alzheimer’s disease (AD). However, the protective effect of Rg1 on neurodegeneration in ADand its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence,western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used toexamine postsynaptic density 95 (PSD95) expression, amyloid beta (Ab) deposition, Tau and phosphorylatedTau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2(NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronaldamage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Ab generation inAPP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression inthe hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Ab deposition byinhibiting NOX2 activation in APP/PS1 mice.

Dysregulated Fatty Acid Metabolism in Hepatocellular Carcinoma

( Ming-da Wang ),( Jun Han ),( Hao Xing ),( Han Zhang ),( Zheng Wang ),( Zhen-li Li ),( Liang Lei ),( Chao Li ),( Feng Shen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Studies are urgently needed on it molecular pathogenesis and biological characteristics of hepatocellular carcinoma (HCC). Dysregulation of fatty acid (FA) metabolism, in which aberrant activation of oncogenic signaling pathways alters the expression and activity of lipid-metabolizing enzymes, is an emerging hallmark of cancer cells, and it may be involved in HCC development and progression. Methods: We summarize the characteristics of FA metabolism in HCC, focusing on the pathways of FA synthesis, oxidation, uptake and transport. We also provide a brief review of the relationship between NAFLD and HCC development. Results: The current review summarizes the dysregulated FA metabolism in HCC and pathways through which this dysregulation may regulate HCC survival and growth. Aberrant activation of oncogenic signaling pathways regulates the expression and activity of lipid-metabolizing enzymes, thus reprogramming FA metabolism to promote HCC development and progression. Intracellular FAs are required for biosynthesis of most biological membrane lipids and signaling molecules, and are also used to provide energy to support HCCs survival and proliferation, when necessary, through β-oxidation process. HCC cells can employ appropriate metabolic pathways as different situation demands. Intrahepatic cholangiocarcinoma (ICC) and HCC exhibits differential requirement for de novo lipogenesis and distinct response to therapeutic approaches focusing on inhibition of exogenous FA uptake. Non-alcoholic fatty liver disease related obesity and diabetes have increasingly emerged as two major factors responsible for the rise in prevalent of HCC. Conclusions: Our understanding of dysregulated FA metabolism and associated signaling pathways may contribute to the development of novel and efficient anti-tumor approaches for patients with HCC.

Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: An Australian Institution’s Experience

Ming Han Lim,Anton R. Lord,Lisa A. Simms,Katherine Hanigan,Aleksandra Edmundson,Matthew J.F.X. Rickard,Russell Stitz,David A. Clark,Graham L. Radford-Smith 대한대장항문학회 2021 Annals of Coloproctolgy Vol.37 No.5

Purpose: We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who had restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at an Australian institution over 26 years.Methods: Data including clinical characteristics, preoperative medical therapy, and surgical outcomes were collected. We divided eligible patients into 3 period arms (period 1, 1990 to 1999; period 2, 2000 to 2009; period 3, 2010 to 2016). Outcomes of interest were IPAA leak and pouch failure.Results: A total of 212 patients were included. Median follow-up was 50 (interquartile range, 17 to 120) months. Rates of early and late complications were 34.9% and 52.0%, respectively. Early complications included wound infection (9.4%), pelvic sepsis (8.0%), and small bowel obstruction (6.6%) while late complications included small bowel obstruction (18.9%), anal stenosis (16.8%), and pouch fistula (13.3%). Overall, IPAA leak rate was 6.1% and pouch failure rate was 4.8%. Eighty-three patients (42.3%) experienced pouchitis. Over time, we observed an increase in patient exposure to thiopurine (P=0.0025), cyclosporin (P=0.0002), and anti-tumor necrosis factor (P<0.00001) coupled with a shift to laparoscopic technique (P<0.00001), stapled IPAA (P<0.00001), J pouch configuration (P<0.00001), a modified 2-stage procedure (P=0.00012), and a decline in defunctioning ileostomy rate at time of IPAA (P=0.00002). Apart from pouchitis, there was no significant difference in surgical and chronic inflammatory pouch outcomes with time.Conclusion: Despite greater patient exposure to immunomodulatory and biologic therapy before surgery coupled with a significant change in surgical techniques, surgical and chronic inflammatory pouch outcome rates have remained stable.

Real-time online optimal control of current-fed dual active bridges based on machine learning

Han, Ming,Liu, Xiaosheng,Pu, Honghong,Zhao, Liang,Wang, Kaixuan,Xu, Dianguo The Korean Institute of Power Electronics 2020 JOURNAL OF POWER ELECTRONICS Vol.20 No.1

This paper proposes a real-time online optimal (RT-OPT) control method based on machine learning for a current-fed dual active bridge (CF-DAB). The basis of this control strategy is the linear quadratic optimal control, which designs the sliding surface and realizes power control based on sliding mode control (SMC). For the parameters of Q and R in the objective function of the linear quadratic regulator (LQR), a genetic algorithm is used to find the optimal value, and the optimal value is taken as the sample data. Through machine learning offline training, a neural network is obtained and run online to realize real-time online optimal control. The control method was verified by simulations in MATLAB/Simulink. The RT-OPT method achieves the expected functionality, and has better dynamic and steady-state performance than the PI controller.

Effective temperature concept evaluated in an active colloid mixture

Han, Ming,Yan, Jing,Granick, Steve,Luijten, Erik National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.29

<P>Thermal energy agitates all matter, and its competition with ordering tendencies is a fundamental organizing principle in the physical world; this observation suggests that an effective temperature might emerge when external energy input enhances agitation. However, despite the repeated proposal of this concept based on kinetics for various nonequilibrium systems, the value of an effective temperature as a thermodynamic control parameter has been unclear. Here, we introduce a two-component system of driven Janus colloids, such that collisions induced by external energy sources agitate the system, and we demonstrate quantitative agreement with hallmarks of statistical thermodynamics for binary phase behavior: the archetypal phase diagram with equilibrium critical exponents, Gaussian displacement distributions, and even capillarity. The significance is to demonstrate a class of dynamical conditions under which thermodynamic analysis extends quantitatively to systems that are decidedly nonequilibrium except that the effective temperature differs from the physical temperature.</P>

Design of A Semi-spherical Microphone Array Based Sound Localization System

Ming-Yuan Shieh,Ming-Hung Tsai,Chin-Chien Chen,Jeng-Han Li 제어로봇시스템학회 2009 제어로봇시스템학회 국제학술대회 논문집 Vol.2009 No.8

This paper proposes a semi-spherical microphone array based sound localization system for a service robot. The hardware of the proposed system basically contains 12 capacitor microphones disposed in two layers on the semi-sphere of 19 cm diameter. It aims to estimate the degree relationship between the main speaker and the robot and provides the robot useful information for more effective human-robot interactions. The proposed system can determine the location of the voice according to energy information between the main speaker and robot not only in normal environment but also in blatant and/or reverberative spaces. The experimental results show that the proposed system has obtained satisfactory recognition efficiency, moreover, raised the robotic friendliness and adaptability.

An Assessment of Qualified Lifeguards’ Knowledge and Attitudes towards Automated External Defibrillator

Ming Han Lim(림밍한),Chanmin Park(박찬민) 한국웰니스학회 2018 한국웰니스학회지 Vol.13 No.2

익사는 사람이 물에 잠겨 호흡기의 장애를 겪는 상황에서 발생하며, 이는 전 세계적으로 의도하지 않은 부상의 원인 중에 3번째로 큰 비중을 차지한다. 대부분의 익사 상황에서 급성심정지 상황은 물에 잠긴 상태로 15분 안에 발생한다. 자동 제세동기는 급성심정지 상태의 환자에게 기본적인 생명 유지 장치이다. 총 3주 동안 12개 시설의 현장 방문을 통해 156부의 설문응답을 바탕으로 싱가포르 인명구조요원들의 자동제세동기에 대한 지식과 태도에 대한 평가를 실시하였다. 본 연구를 통하여 얻어진 결과에 따르면, 싱가포르 인명구조요원들은 일반적으로 자동제세동기에 대한 지식이 부족하고, 자동제세동기의 사용에 대하여 부정적인 태도를 가지고 있으며, 관련 법률에 대하여서도 잘 알지 못하였다. 인명구조요원에게 자동제세동기 운용 자격증을 의무화 하는 것이 자동제세동기를 사용함에 자신감을 높일 수 있게 할 것이다. 아울러, 법률적 책임으로부터 명확하게 보호 받을 수 있는 제도적 장치는 인명구조요원들의 자동제세동기 사용에 대한 의지를 높일 수 있게 할 것이다. Drowning occurs when a person suffers respiratory impairment from being submersed in liquid, and it is the 3rd largest cause of unintentional injury death globally. In most drowning situations, cardiac arrest occurs within 15 minutes of being submerged. The Automated External Defibrillator (AED) is a fundamental equipment for basic life support for sudden cardiac arrest victims. Total 156 valid surveys were collected through on-site visits carried out at 12 facilities over a 3-week period to access of qualified lifeguards’ knowledge and attitudes towards AEDs in Singapore. Results show that lifeguards in Singapore generally had poor knowledge on AEDs, a negative attitude towards AED usage and were poorly informed on AED and lifesaving legislation. Making AED certification compulsory for lifeguards would likely increase their confidence in using AEDs. Moreover, clarification regarding protection from legal liability should be provided to increase lifeguards’ willingness to use AEDs.

Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer

Hou Ming-Feng,Ou-Yang Fu,Li Chung-Liang,Chen Fang-Ming,Chuang Chieh-Han,Kan Jung-Yu,Wu Cheng-Che,Shih Shen-Liang,Shiau Jun-Ping,Kao Li-Chun,Kao Chieh-Ni,Lee Yi-Chen,Moi Sin-Hua,Yeh Yao-Tsung,Cheng Chi 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory

Zhao, Ming-Gao,Toyoda, Hiroki,Lee, Yong-Seok,Wu, Long-Jun,Ko, Shanelle W.,Zhang, Xue-Han,Jia, Yongheng,Shum, Fanny,Xu, Hui,Li, Bao-Ming,Kaang, Bong-Kiun,Zhuo, Min Elsevier 2005 Neuron Vol.47 No.6

<P><B>Summary</B></P><P>Cortical plasticity is thought to be important for the establishment, consolidation, and retrieval of permanent memory. Hippocampal long-term potentiation (LTP), a cellular mechanism of learning and memory, requires the activation of glutamate N-methyl-D-aspartate (NMDA) receptors. In particular, it has been suggested that NR2A-containing NMDA receptors are involved in LTP induction, whereas NR2B-containing receptors are involved in LTD induction in the hippocampus. However, LTP in the prefrontal cortex is less well characterized than in the hippocampus. Here we report that the activation of the NR2B and NR2A subunits of the NMDA receptor is critical for the induction of cingulate LTP, regardless of the induction protocol. Furthermore, pharmacological or genetic blockade of the NR2B subunit in the cingulate cortex impaired the formation of early contextual fear memory. Our results demonstrate that the NR2B subunit of the NMDA receptor in the prefrontal cortex is critically involved in both LTP and contextual memory.</P>