Circulating myokine levels in different stages of glucose intolerance

Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients.A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups.Irisin level showed a tendency to increase in prediabetes group compared to normal group (P < .1) but showed a significant decrease when comparing diabetes from prediabetes group (P < .001). IL-13 decreased in diabetes group compared to prediabetes and normal group (P < .001, P < .05, respectively). FSTL-1 of diabetes group was lower than that of prediabetes group (P < .05), and fractalkine was higher in diabetes group compared to that of prediabetes and normal group (P < .01, P < .01, respectively).Irisin, IL-13, and FSTL-1 levels were reduced in diabetes group compared to normal or prediabetes group while fractalkine showed a progressive increase from normal to diabetes group. Further studies are warranted to study the roles of various myokine in diabetes through a larger prospective study.ope

Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. Methods: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. Results: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. Conclusion: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.ope

향상된 NGS 분석 방법을 사용한 순환 종양 DNA 분석

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 2. 묵인희.Introduction: Interrogation of circulating tumor (ct)DNA using next-generation sequencing (NGS)-based methods have been proposed as a way to track the dynamics of tumor in real time. However, there was no standard guideline for ctDNA sequencing that I have evaluated the procedure from end-to-end to propose the optimal analysis methods for ctDNA sequencing. Chapter 1* emphasizes the importance of the recovery of unique DNA molecule from the minimal amount of starting material. After that, the systematic evaluation of each step highlights the error-prone step in the sequencing process. In Chapter 2, the utility of ctDNA sequencing has evaluated through the monitoring of tumor genomic in multi-cancer samples. Method: To maximize the recovery rate of unique DNA molecule, I approached the ligation step during the library preparation in sequencing protocol by optimizing the temperature, time and adapter concentration. Identification of technical errors was conducted with the comparison of background error distribution from the acoustically sheared germline DNA and naturally fragmented cell-free DNA. The utility of ctDNA sequencing analysis was assessed by comparing the standard protein biomarker and imaging changes during the patients therapeutic intervention. Results: The modified ligation conditions for the minimal amount of starting material able to increase the recovery rate of unique DNA molecule by 20% compared to the standard conditions. A comparison of the characteristic of acoustically sheared gDNA and naturally fragmented cfDNA revealed that gDNA constituted with 64% of C: G> A: T and 39% of C: G> G: C substitution class changes. Through testing of the series of the mild sheared conditions, the reduction of error rate was observed with an average of 40%. Furthermore, the analysis of the vicinity at the ends of the DNA fragments revealed that A> G and A> T preferentially fragmented. The enhanced analytical performance in NGS method able to establish diagnostic utility with the detection sensitivity of 100% and specificity of 97.1% as applied to cancer plasma samples. The level of ctDNA was not only highly correlated with the therapeutic response but also showed an average of two months earlier reaction than the standard protein biomarker and imaging changes. Finally, the determination of tumor heterogeneity was observed through ctDNA analysis, which was not discovered in the matched tumor biopsies. Conclusions: Overall, the unique characterization of cfDNA could not only emphasize the underlying cause of technical errors but also demonstrate opportunities for early detection of cancer using NGS-based technology. Ultimately, the combined approach of ctDNA and NGS sequencing analysis is believed to address unmet needs in cancer research.GENERAL INTRODUCTION 1 Cell-free DNA 3 Circulating tumor DNA 4 Current detection methods for ctDNA 4 Digital PCR 4 Next generation sequencing 5 NGS-based ctDNA analysis 7 Potential misdiagnosis from background errors 8 CHAPTER1 Practical guidelines for cell-free DNA analysis using enhanced analytical performance of NGS-based method 15 INTRODUCTION 15 MATERIALS AND METHODS 18 RESULTS 22 Comparison of blood collection tubes 22 Optimization of library preparation 22 Optimizing statistical modeling for cfDNA analysis 24 Performance of optimized TDS on cfDNA and PBL DNA 24 Estimation of errors derived by TDS 25 From sequencing reaction 25 Distribution of background errors 25 Sample preparation caused background errors 26 Breakpoint preferences 27 Multi-statistical adjustment for removing the background errors 29 DISCUSSION 31 CHAPTER 2 Ultrasensitive interrogation of circulating tumor DNA from cancer patients using enhanced analytical performance of the NGS-based method 51 INTRODUCTION 58 MATERIALS AND METHODS 54 RESULTS 61 Evaluation of LOD with single mutation 61 KRAS mutations 61 Evaluation of LOD with multi-mutations 61 With primary mutation 61 Biopsy-free manner 62 Monitoring tumor burden by measuring ctDNA 63 Diagnostic utility 65 DISCUSSION 67 GENERAL DISCUSSION 94 REFERENCES 95Docto

Relationship Between Natural Killer Cell Activity and Glucose Control in Patients With Type 2 Diabetes and Prediabetes

Aims/introduction: Natural killer (NK) cells are cytotoxic lymphocytes critical to human immunity. Previous studies showed correlations between NK cell function and blood glucose concentrations. The purpose of the present study was to assess the NK cell activity and various metabolic parameters in people with type 2 diabetes, prediabetes and normal glucose tolerance. Materials and methods: A total of 49 participants were enrolled in the study. Anthropometric and biochemical parameters including age, sex, body mass index, smoking status, blood pressure, fasting plasma glucose, C-peptide, insulin, glycated hemoglobin, total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were assessed. The 75 g oral glucose tolerance test was carried out for 2-h postload glucose level. Homeostatic model assessment was calculated for insulin resistance and β-cell function. NK cell activity was measured by detecting the circulating interferon-gamma level secreted from NK cells. Results: NK cell activity was lower in patients with type 2 diabetes (768.01 ± 650.35) compared with those with prediabetes (2,396.08 ± 653.76, P < 0.001) and normal glucose tolerance (2,435.31 ± 633.22, P < 0.001). In patients with type 2 diabetes, there was a significant inverse linear relationship between NK cell activity and fasting plasma glucose, glycated hemoglobin, and 2-h postload glucose level (all P < 0.001). Multiple regression analysis showed glycated hemoglobin to be an independent predictor of NK cell activity in patients with type 2 diabetes. Conclusions: Compared with individuals with normal glucose tolerance or prediabetes, type 2 diabetes patients have a reduced NK cell activity, and it is significantly related to glucose control.ope

Association between atherogenic index of plasma and coronary artery calcification progression in Korean adults

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and few cross sectional studies have demonstrated a relationship between AIP and coronary artery disease. The present study investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. Methods: A total of 1124 participants who had undergone CAC measurement at least twice by multi-detector computed tomography (CT) at a health check-up center were enrolled. Their anthropometric measurements and various cardiovascular risk factors were assessed. AIP was defined as the base 10 logarithm of the ratio of the concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). CAC progression was defined as either incident CAC in a CAC-free population at baseline, or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) in subjects with detectable CAC at baseline. Results: CAC progression was observed in 290 subjects (25.8%) during the mean follow-up of 4.2 years. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with rising AIP tertiles. In logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of AIP (95% CI: 1.61-3.19; P for trend < 0.01). However, this association was attenuated after adjustment for multiple risk factors (P for trend = 0.67). Conclusions: There is a significant correlation between AIP and the progression of CAC in subjects without CVD. Although AIP was not an independent predictor of CAC progression, AIP should be considered when estimating the current as well as future CVD risk, along with other traditional risk factors.ope

Triglyceride Glucose Index Is Superior to the Homeostasis Model Assessment of Insulin Resistance for Predicting Nonalcoholic Fatty Liver Disease in Korean Adults

BACKGROUND: Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults. METHODS: Participants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography. RESULTS: Significant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend <0.01), respectively. According to the receiver operating characteristic analysis, the TyG index was superior to HOMA-IR in predicting NAFLD. CONCLUSION: The TyG index and prevalence of NAFLD were significantly related and the TyG index was superior to HOMA-IR in predicting NAFLD in Korean adults.ope

Conjoint Analysis for increasing precision of the response

컨조인트 분석은 기업의 마케팅 담당자들이 신제품의 선호도를 조사해서 신제품의 컨셉을 정하고자 할 때 주로 사용된다. 설문지 문항을 구성할 때 실험계획법의 요인설계를 사용할 수 있다. 블록화 혼합수준 요인설계를 사용하고 응답자를 블록으로 간주하면 응답자간에 설문지 문항이 다르게 된다. 즉 블록이 응답자가 되고 블록크기가 응답자별 문항수가 된다. 이 때 고려하고자 하는 속성들이 많으면 한 문항 당 묻게 되는 속성의 수가 많아지고 응답자들은 자신의 선호도를 정확하게 점수화하기 어려워질 수 있다. 즉 비표본오차가 생길 수 있다. 본 논문에서는 컨조인트 분석에서 속성들의 수가 많은 블록화 혼합수준 요인설계를 사용할 때, 속성들의 병합을 통해 문항당 묻는 속성의 수를 줄여 응답의 정확도를 높일 수 있는 방법에 대해 제안한다. 수준수가 서로 다른 속성 두 개와 ‘묻지 않음’을 병합하여 새로운 수준으로 간주해서 설계를 생성하고 원래의 수준으로 다시 풀어서 설계를 완성한다. 이후의 절차는 기존의 블록화 혼합수준 요인설계의 절차와 동일하다. 제안한 방법을 사용할 경우 한 문항에서 묻게 되는 속성의 수가 전체 속성의 수의 절반이하로 줄어들기 때문에 응답자에게 더욱 일관된 응답을 기대할 수 있다. 본 논문에서는 블록화 혼합수준 요인설계 중 속성이 8개인 경우인 블록화 2^(4)x3^(4) 설계와 블록화 3^(4)x5^(4) 설계에 대해 각각 제안한 설계를 만드는 방법과 적절한 변수선택법을 통해 유의한 효과를 찾는 방법을 설명하고, 시뮬레이션을 통해 제안하는 방법의 효율성을 평가한다.;Conjoint analysis is often used by corporate marketers to explore the preferences of new products and to define new product concepts. When you configure questionnaire items, the factorial design of the design of experiment can be used. If the blocked mixed level factorial design is used and the respondents are regarded as blocks, the questionnaire items are different among the respondents. If there are many attributes to be considered, there will be more attributes to be asked per question, and respondents will have difficulty scoring their preferences accurately. That is, non-sampling error may occur. In this paper, we propose a method to increase the accuracy of response when using blocked mixed level factorial design with a large number of attributes in conjoint analysis. The design is completed by merging two attributes with different levels and &amp;apos;not asking&amp;apos;, considering them as a new level, creating the design and releasing it back to its original level. The subsequent procedure is identical to the procedure of original blocked mixed level factorial design. Using the proposed method, the number of attributes to be asked in one question is reduced to less than half of the total number of attributes, so more consistent response can be expected to the respondent. In this paper, we describe how to create the proposed designs of the blocked 2^(4)x3^(4) design and the blocked 3^(4)x5^(4) design and find out the meaningful effects through the appropriate variable selection method, evaluate the effectiveness of the proposed method through simulation.Ⅰ. 서론 1 A. 연구의 목적 1 B. 컨조인트 분석에서 기존의 블록화 혼합수준 요인설계 2 Ⅱ. 블록화 혼합수준 요인설계시 속성병합 방법 3 A. 제안하는 방법 3 B. 실험점 생성 방법 7 1. 블록화 2^(4)x3^(4) 설계분석을 위한 블록화 6^(4) 설계 9 2. 블록화 3^(4)x5^(4) 설계분석을 위한 블록화 9^(4) 설계 13 Ⅲ. 시뮬레이션을 통한 제안한 방법의 효율성 15 A. 유의한 효과 선택방법 15 B. 시뮬레이션 가정 20 1. 블록화 2^(4)x3^(4) 설계 20 2. 블록화 3^(4)x5^(4) 설계 21 C. 시뮬레이션 결과 및 비교 22 1. 제안한 블록화 2^(4)x3^(4) 설계 23 2. 제안한 블록화 3^(4)x5^(4) 설계 25 Ⅳ. 결론 28 참고문헌 29 부록1. 설계를 생성하는 SAS 코드 30 부록2. 변수선택법함수 R-code 34 부록3. 시뮬레이션 R-code 38 ABSTRACT 4

테넬리글립틴 투여가 고지방식이로 유발된 당뇨비만 생쥐의 다양한 대사기관에서의 DNA 손상에 미치는 영향

Both diabetes mellitus (DM) and obesity are characterized by hyperinsulinemia and higher incidence of microvascular complication, cardiovascular disease, and many kinds of cancer. Obesity and constant hyperglycemia increase oxidative stress and inflammation, resulting in loss of balance between DNA double strand break (DSB) and DNA damage response (DDR), and various clinical diseases such as diabetic complication, cardiovascular disease and cancer can occur. When cells are exposed to harmful stimuli, DSB occurs and DDR begins. Mammalian eukaryotic cells repair DSBs primarily by two mechanisms of DDR; non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ, which appears at the time of metabolic damage, use many proteins such as Ku, DNA-dependent protein kinase catalytic subunit, XRCC4, DNA ligase IV, and XRCC4-like factor. Glucagon-like peptide-1 (GLP-1) not only shows anti-diabetic effect, but also shows multiple organ protective effects such as neuroprotection in brain and kidney protection in recent studies. Dipeptidyl peptidase-IV (DPP-IV) inhibitor, which inhibits DPP-IV and prolongs GLP-1 effect, is more widely used around the world than GLP-1 receptor agonist, but the study on DPP-IV inhibitor’s organ protective effects has not conducted yet. In this study, we aimed to investigate not only glycemic control effect but also organ protective effects of DPP-IV inhibitor, using teneligliptin to high fat diet (HFD)- induced diabetic obese mice. Mice were classified into five groups according to HFD and dose of teneligliptin administration. Teneligliptin showed improvement of glucose regulation capacity, and this is assumed to be because of attenuated hepatic gluconeogenesis increase and protected insulin secretion capacity. HFD-induced obese mice showed higher levels of NHEJ proteins in multiple metabolic organs, indicating more DNA damage occurred in diabetic obese condition compared to normal control group. Furthermore, we showed decreased DNA damage in multiple metabolic organs and kidney which is an important target organ after teneligliptin administration, and proved teneligliptin’s organ protective effects.open박

Analysis on Factors of China's Non-alliance: Protection Sovereignty and Past Alliance Experience

학위논문 (석사)-- 서울대학교 대학원 : 정치외교학부(외교학전공), 2013. 8. 정재호.국제정치에서 강대국들은 약소국을 효율적으로 관리하기 위하여 동맹조약을 활용하며 대부분의 강대국들은 보편적으로 동맹을 결성하고 있다. 그러나 중국은 1949년 건국 이후부터 2013년 현재까지 소련과 북한을 제외하고 어느 국가와도 동맹을 맺지 않고 있다. 이와 같은 양상은 1982년 독립자주의 대외정책과 1984년 동맹 불체결(不結盟)을 발표하면서 더욱 명확하게 드러났다. 본 연구에서는 이처럼 중국이 보편적인 강대국과 달리 동맹을 결성하지 않고 있는 것에 문제의식을 갖고 중국의 동맹 불체결의 요인을 살펴보았다. 중국은 1950년 2월에 소련과 『중소우호동맹호조조약』을 체결하였으며 1961년 7월에는 북한과 『중조우호협력호조조약』을 맺었다. 중국은 중·북 동맹 결성 이후 현재까지 어떠한 동맹도 결성하지 않은 것은 물론 1984년에 동맹 불체결을 선언한 이후 전국대표대회 보고서와 국방백서 등을 통해 지속적으로 이에 대한 자국의 입장을 명확히 표명하였고 그 원칙을 고수하고 있다. 이처럼 중국이 동맹을 결성하지 않은 원인으로 본 연구에서는 다음의 두 가지 요인을 검토하였다. 첫째, 동맹 결성으로 인해 주권이 침해당할 수 있으며 주권 침해를 최소화하려는 중국의 다양한 모습들을 살펴볼 수 있다. 중국은 주권 수호에 대하여 강한 의지를 보이는데 동맹을 결성하면 주권이 위협받을 가능성이 높아지기 때문에 동맹조약을 체결하지 않는다는 것이다. 동맹을 결성할 경우 동맹 체결국 간에는 상호 정책 결정에 영향력을 행사할 수 있는 기제가 마련되며 이러한 양상은 비대칭 동맹에서 더욱 뚜렷하게 나타난다. 중국은 과거 중·소 동맹으로 인해 자국의 주권이 침해받았다고 여겼으며 이와 같은 중국의 인식은 중국 지도자들의 발언을 통해 알 수 있다. 중국이 동맹을 결성하지 않는 두 번째 요인으로 동맹 와해의 경험을 살펴볼 수 있으며 본 연구에서는 과거 중·소 동맹의 와해를 중심으로 이를 검토하였다. 대부분의 동맹에서는 동맹 딜레마가 발생하는데 중국은 중·소 동맹을 통하여 이러한 딜레마를 겪게 되었다. 중국은 다른 국가와 군사적 충돌이 발생하였을 때 동맹국에 기대하였던 충분한 지지를 확보하지 못하였으며 오히려 동맹 파트너가 자국에 적대적인 국가와 협력을 도모하는 등 여러 차례에 걸쳐 동맹으로부터 이익을 얻지 못했다. 또한 중국은 동맹을 통해 외부의 위협을 제거하려 했지만 이러한 목표 역시 달성되지 않았고, 1960년대 후반에는 소련과 군사적 충돌을 겪기도 하였다. 이와 같은 경험은 중국에게 동맹이 여러 가지 측면에서 국익을 도모하는 데 결코 효율적인 수단이 아님을 인식시켰다. 본 연구에서 살펴본 중국의 동맹 불체결 요인은 중국의 유일한 동맹국인 북한과의 관계를 이해하는 데에도 일정 부분 함의를 준다. 북한은 중국보다 상대적으로 약소국이기 때문에 중국의 주권을 침해할 가능성은 매우 낮으며 중·북 동맹이 체결된 이후 중국은 북한으로부터 연루와 방기를 경험하지 않았다. 이를 종합하여 보았을 때 지금까지 중·북 동맹이 유지되고 있는 것은 본 연구에서 검토한 요인들이 작용한 결과라고 유추해볼 수 있다. 중국과 같이 주권 수호의 의지가 강한 국가는 극심한 위협에 처해 있지 않은 이상, 주권이 훼손될 여지가 있는 동맹을 결성할 가능성이 낮다. 또한 과거에 동맹의 와해를 경험한 적이 있는 국가라면 이를 반면교사로 삼을 것이고 이후 동맹조약을 체결할 유인은 더욱 줄어들 것이다. 주권 침해의 가능성과 동맹의 딜레마라는 동맹의 본질적인 문제가 있기에 중국이 동맹 불체결의 원칙에서 탈피하여 동맹을 결성할 가능성은 낮은 것으로 보인다. 이와 같은 중국의 동맹 불체결 요인에 대한 분석은 향후 중·북 관계에 대해 일정 부분 시사점을 제공한다고 볼 수 있다.The purpose of this research is to explain why China have not aligned with any country. Most great powers forged alliance that regarded as a universal phenomenon in international politics. Since the establishment of the China in 1949, China aligned with both Soviet Union and North Korea. These aspects appeared by announcing the so-called independent and autonomous diplomacy in 1982 and non-alliance in 1984. This study analyzed on Sino-Soviet alliance and Sino-North Korean alliance. The Sino-Soviet Treaty of Friendship, Alliance and Mutual Assistance was signed on February, 1950. In July, 1961, when the China and the North Korea signed a treaty of friendship, cooperation and mutual assistance. From that time onward China have not aligned with any country which aspects could confirmed through the official document of Chinas National Peoples Congress or White Paper on Chinas National Defense. Two factors can be identified for Chinas non-alliance. First, China has a strong will to protect their sovereignty and thus China is very hesitant to sign an alliance treaty. When it comes to forming an alliance involved party countries in the alliance will have a certain mechanism to influence on domestic policy makings. This will be more distinct in asymmetrical alliance relations. In Chinese perspective, Sino-Soviet alliance was the one which severely interfered Chinas sovereignty, which can be clearly indicated in utterance of Chinas sovereignty, which can be clearly indicated in utterance of Chinese politicians. In this research, Chinas strong will to protect their sovereignty is shown both in frequency of utterance and contents analysis of it, by closely analyzing the official document of National Congress of Communist Party of China and National Peoples Congress. The second factor in Chinas non-alliance is the experience of collapse of the alliance. Sino-Soviet alliance collapse is one of representative examples of it. Most of alliance almost inevitably brings alliance dilemma: not only cannot a nation in alliance with another receive enough support in international conflict or security, but also it cannot get rid of external threats completely. Additionally, experience of political and military conflicts with Soviet Union made China perceive alliance is not an efficient mean to defend against hostile country or improve status of nation in international politics. Closely observing the factors of Chinas non-alliance gives certain implication, though partial, in the relationship between North Korea and China. North Korea, with its weaker status than that of China, has lower probability to interfere Chinas sovereignty. China did not experience any entrapment or abandonment with/from North Korea. These two factors explains why North Korea-China alliance is still in effect. A nation with a definitely strong will go guard their sovereignty such as China shows low probability to form an alliance which would interfere its sovereignty unless faced with critical threats. Especially when a nation already has a great deal of experience of alliance collapse, the lesson they had learned would have had lingering effects in their policy making, reducing the incentive to go into alliance treaty. With sovereignty interference problem and alliance dilemma unresolved, China is highly unlikely to commit themselves to non-alliance principle.Ⅰ. 서론 ……………………………………………………………‥‥ 1 1. 연구질문의 규명 ………………………………………………‥ 1 2. 기존연구 분석 …………………………………………………‥ 9 a)중국의 동맹 불체결 요인에 대한 기존연구 ………… 9 b)중·소 동맹과 중·북 동맹에 대한 기존연구 …………‥ 14 3. 연구 설계: 연구 시기와 가설 설정 ………………………… 17 a) 연구 대상 및 시기 ……………………………………‥‥ 17 b) 가설 설정 ………………………………………………‥‥ 19 4. 논문의 구성 …………………………………………………… 23 Ⅱ. 주권에 대한 집착과 동맹 불체결 …………………………… 25 1. 동맹과 주권의 관계 …………………………………………… 25 2. 중국의 주권 수호에 대한 의지 ……………………………… 31 3. 중·소 동맹과 주권 침해 …………………………………‥ 40 4. 소결 ……………………………………………………………… 47 Ⅲ. 동맹 와해의 경험과 동맹 불체결 …………………………‥ 51 1. 동맹 파트너로부터의 방기 …………………………………‥ 51 2. 동맹국으로부터의 군사 위협의 증대 ……………………… 61 3. 동맹 딜레마의 부재와 동맹의 유지 ……………………… 67 4. 소결 ……………………………………………………………… 72 Ⅳ. 결론 ……………………………………………………………… 77 1. 연구 요약 …………………………………………………‥‥ 77 2. 연구의 함의 …………………………………………………‥ 80 참 고 문 헌 …………………………………………………………… 83Maste

The effect of Korean Red Ginseng on sarcopenia biomarkers in type 2 diabetes patients

Background: The elderly population is growing rapidly worldwide and sarcopenia, which is considered as a new geriatric syndrome has become an important issue. In particular, diabetes is known to be an important risk factor for sarcopenia. In this study, we investigated the effects of Korean Red Ginseng (KRG) on biomarkers of sarcopenia in middle and old age diabetes patients. Patients and methods: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in sarcopenia biomarkers at week 24. Secondary outcomes were changes in inflammatory and antioxidant markers and lean body mass at week 24. Results: Fifty-nine patients completed the study. Follistatin and sex hormone binding globulin (SHBG) were significantly improved in KRG group. In the subgroup analysis, female postmenopausal patients over the age of 55 showed a significant improvement in serum SHBG, follistatin, and growth differentiation factor 15 (GDF-15) and an attenuated reduction in Troponin T (TNT) after the administration of KRG. Conclusion: Twenty-four week administration of KRG in diabetes patients resulted in a significant improvement in follistatin and SHBG levels, especially in old postmenopausal women. A further, larger population study with a longer follow-up period is warranted to verify and understand the effects of KRG on sarcopenia.restrictio