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암관련섬유모세포 유래 GAS6가 위암 세포의 AXL/STAT3/ABCG1 신호 전달을 통해 항암화학요법 저항성 증가에 관여하는 기전과 그 억제방안에 대한 연구
No full textDoctorI. INTRODUCTION 1
II. MATERIALS AND METHODS 4
1. Cell lines and cell culture 4
2. Preparation of conditioned media (CM) 4
3. Co-culture with GC cells and treatment 4
4. Transwell migration assay 5
5. Cell viability assay 5
6. RNA isolation and quantitative reverse transcriptase PCR (qRT-PCR) 6
7. Reverse transcriptase PCR (RT-PCR) 6
8. Enzyme-linked immunosorbent assay (ELISA) 7
9. Flow cytometry 8
10. Western blotting 8
11. Drug efflux assay 9
12. Luciferase assay 10
13. Immunocytochemistry (ICC) 11
14. Immunohistochemical staining (IHC) 11
15. Small interfering RNA (siRNA) 12
16. Animal model study 12
17. Microarray 13
18. Public data 13
19. Statistical analysis 14
III. RESULTS 15
1. 9im inhibits activation of AXL by CAFs-derived GAS6 in GC cells 15
2. Comparison between the effects of BGB324 and 9im in the viability of non- cancerous cells and inhibition of AXL activation in GC cells 23
3. The GAS6/AXL axis signaling pathway was essential in CAFs-induced migration of GC cells 26
4. Combined treatment of 9im and chemotherapeutic agents suppressed the CAFs-induced chemoresistance in GC cells 29
5. Genetic inhibition of GAS6/AXL axis suppresses the CAFs-induced chemoresistance in GC cells 39
6. ABCG1 is a key molecule of CAFs-induced chemoresistance in GC cells 50
7. ABCG1 and GAS6 expression is associated with poor prognosis in GC patients 67
IV. DISCUSSION 72
V. REFERENCES 76
국문요약 8
플레이오트로핀과 senescence의 연관성
No full textMasterⅠ. 소개 1
1. 노화의 중요성 1
2. 노화의 정의 2
3. 플레이오트로핀의 정의 6
4. 플레이오트로핀의 유전자 발현 조절자 7
Ⅱ. 플레이오트로핀의 수용체 9
1. PTPRZ 12
2. 신데칸 13
3. 뉴클레오린 15
4. 인테그린 αVβ3 16
5. 인테그린 αMβ2 (Mac-1) 17
Ⅲ. 플레이오트로핀의 기능들 18
1. 뉴런 발달 21
2. 희소돌기아교세포 분화 22
3. 혈관신생 23
4. 염증 및 상처 23
5. 뼈 발달 24
6. 지방세포 분화 25
7. 유방 상피세포 분화 25
Ⅳ. 플레이오트로핀과 senescence와의 연관성 27
1. 플레이오트로핀의 항산화 효과 29
2. 플레이오트로핀의 역노화 효과 30
3. 플레이오트로핀과 알츠하이머 병 30
4. 플레이오트로핀과 혈관계 31
5. 플레이오트로핀과 골관절염 33
6. 플레이오트로핀과 당뇨병 34
Ⅴ. 플레이오트로핀과 암 36
1. 교모세포종 38
2. 유방암 39
3. 폐암 39
4. 난소암 40
5. 췌장암 40
6. 플레이오트로핀과 암의 전이 41
7. 플레이오트로핀과 암의 예후 42
Ⅵ. 플레이오트로핀의 조절을 통한 연구 44
1. 플레이오트로핀의 억제제의 개발 44
2. 플레이오트로핀의 과발현을 통한 fruit fly의 수명연장 44
Ⅶ. 토론 45
Ⅷ. 결론 46
Ⅸ. 참고문헌 4
Non-invasive PCO₂ Monitoring during Polysomnography: Transcutaneous versus End-tidal Measurement
No full textMasterAbstract I
Table of Contents III
List of Figures IV
List of Tables V
I. Introduction 1
II. Methods 3
A. Ethics statements 3
B. Study design and subjects 3
C. Data collection 3
D. Statistical analysis 4
III. Results 5
IV. Discussion 7
A. Principal results and strengths of the study 7
B. Measuring PEtCO₂ 8
C. Measuring PTcCO₂ 9
D. Comparison with other studies 10
V. Conclusions 12
VI. Figures 13
VII. Tables 20
References 29
국문초록 3
Usefulness of digital single-operator cholangioscopy for biliary diseases: a look back to move forward
No full textMasterI. INTRODUCTION 1
II. METHODS 2
A. Patients 2
B. Endoscopic procedure 2
C. Outcome measurements and definition 2
D. Statistical analyses 3
III. Results 4
IV. Discussion 6
V. References
Hip, Abdomen and Paraspinal Muscle Morphology and its Effect on Pain and Disability in Patients with Degenerative Lumbar Scoliosis
No full textMasterI . Introduction 1
I I . Methods 3
A. Study design 3
B. Evaluation of pain and disability 4
C. Evaluation of coronal and sagittal radiographic parameters 4
D. Evaluation of core muscle morphology 5
E. Statistical analysis 9
I I I . Results 10
A. Patient demographics 10
B. Effect of core muscle morphology on pain and disability scores 13
C. Association of core muscle morphology with radiographic parameters 16
IV. Discussion 18
V. Conclusion 2
Mechanical versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 to 70 Years
No full textBACKGROUND: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. METHODS: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. RESULTS: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07-1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28-0.67; p<0.001) and anticoagulation- related bleeding (sHR, 0.35; 95% CI, 0.23-0.53; p<0.001) in the bioprosthetic AVR group. Conversely, the risk of aortic valve (AV) reintervention was higher in the bioprosthetic AVR group (sHR, 6.14; 95% CI, 3.17-11.93; p<0.001). CONCLUSION: Among patients aged 50 to 70 years who underwent surgical AVR, those receiving mechanical valves showed better survival than those with bioprosthetic valves. The mechanical AVR group exhibited a higher risk of stroke and anticoagulation-related bleeding, while the bioprosthetic AVR group showed a higher risk of AV reintervention
기능의학 의사가 고려해야 할 고코르티솔증의 임상적 평가 및 치료
No full textHypercortisolism is a phenomenon identified in traditional medicine for Cushing's syndrome, an endocrine disease, but is commonly discovered during clinical evaluation in functional medicine. Endogenous Cushing's syndrome itself is an uncommon disease, but if not properly evaluated, it can cause various complications in patients, so early detection and treatment are important. Additionally, pseudo-Cushing's syndrome, which may appear to be Cushing's syndrome, is often closely related to mental illness and stress reactions. As a functional medicine physician, it is important to understand cortisol metabolism and testing methods to evaluate hypercortisolism, and it is necessary to consider various patient’s conditions and solutions when hypercortisolism is confirmed.고코르티솔증은 전통의학적으로 내분비질환인 쿠싱증후군에서 확인되는 현상이나 기능의학적 임상적 평가과정에서 흔히 발견되는 현상이다. 내인성 쿠싱증후군자체는 흔하지 않은 질환이나 평가되지 않은 경우 환자에게 다양한 합병증을 갖게 되어 조기 발견 및 치료가 중요하다. 또한 쿠싱증후군으로 보일 수 있는 많은 가성 쿠싱 증후군의 경우 정신질환 및 스트레스 반응과 밀접한 관련이 되어 있다. 기능의학 의사로서 고코르티솔증의 평가에 대한 코르티솔 대사 및 검사방법에 대한 이해가 중요하며 고코르티솔증을 확인하였을 때 감별해야 할 환자의 상태와 그 해결법에 대한 다양한 고민이 반드시 필요하다
Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021
Get PDFBackground: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. Funding: Bill & Melinda Gates Foundation
Determining the Optimal Dosage of Dexmedetomidine for Smooth Emergence in Older Patients Undergoing Spinal Surgery: A Study of 44 Cases
Get PDFBackground: Emergence agitation, or delirium, occurs during early recovery from general anesthesia and involves disorientation, excitation, and uncontrolled physical movements. Dexmedetomidine is an alpha agonist that has sedative, anxiolytic, analgesic, and sympatholytic activities and is used as a continuous infusion to prevent emergence agitation. This study aimed to evaluate patients aged 65 years and older undergoing general anesthesia to determine the 90% effective dose (ED90) of dexmedetomidine continuous intraoperative infusion to prevent emergence agitation. Material/Methods: We enrolled 44 patients aged 65 years and older undergoing spinal surgery under general anesthesia. Dexmedetomidine administration commenced 30 minutes before surgery completion, with a predetermined infusion dose (μg/kg/h), without a loading dose. The initial dose was 0.2 μg/kg/h, and subsequent step size was ±0.05 μg/kg/h. We tried to find ED90 of dexmedetomidine using the biased-coin design. Vital signs, extubation quality scores, extubation-related complications, and postoperative outcomes were monitored. Results: Dexmedetomidine ED90 for smooth emergence in older patients was 0.34 μg/kg/h. Peri-extubation vital signs remained within 20% of baseline values, without requiring pharmacological intervention. No hypoxia, hypoventilation, or post-extubation agitation occurred. In the recovery room, 1 patient briefly exhibited excitement but quickly calmed. Nine patients initially unresponsive in the recovery room fully awoke and were promptly discharged. Conclusions: For older patients who are vulnerable to adverse effects of anesthetics and opioids, dexmedetomidine enables gentle awakening without adverse vital sign changes, respiratory depression, excessive sedation, or emergence agitation (ED90=0.34 μg/kg/h). Further studies should involve a larger patient cohort, considering diverse medical conditions in older individuals
Changes in the expression of cell interaction-related pathways during brain metastasis in lung adenocarcinoma: Gene expression and immunohistochemical analysis
No full textBackground: Brain metastasis (BM) is a prevalent prognostic event in the development of lung adenocarcinoma (LUAD) with a poor prognosis. Alterations in gene or protein expression during various phases of BM remain unclear. Methods: We performed gene expression and pathway analyses using a metastasis-related gene panel on 12 lung tissues from patients with confirmed BM, 12 lung tissues from patients without BM, and 12 matched brain tissues from patients with confirmed BM during follow-up after LUAD surgery. The results of the gene expression analysis were validated by immunohistochemistry. Results: Cell interaction-related pathways (such as focal adhesion, extracellular matrix-receptor interaction, and proteoglycans in cancer) showed the greatest differences among the three groups. Expression of the cell interaction-related pathway was highest in the lung sample of BM group and lowest in the matched brain tissue. Using a machine learning model, a signature of 20 genes from cell interaction-related pathways accurately predicted BM (area under the curve score of 0.792 and an accuracy rate of 0.875). Immunohistochemical analysis showed higher expression of proteins associated with cell interaction-related genes and a mesenchymal phenotype in the lung sample of BM group than in those without BM or matched brain tissue. Conclusions: LUAD acquires the characteristics of the cell interaction-related pathway that leads to the development of BM, with a significant decrease in expression following brain colonization