ABSTRACT
BACKGROUND: The escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD. METHODS: Medline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95â¯% confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally. RESULTS: The systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68-1.26) for cohort studies and a pooled RR of 0.97 (0.41-2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03-1.13) for ADHD in the ART group compared to the non-ART group. CONCLUSION: While this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation.
ABSTRACT
BACKGROUND: Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy. METHODS: The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights. RESULTS: We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56). CONCLUSIONS: While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy. SYSTEMATIC REVIEW REGISTRATION: CRD42022342510.
Subject(s)
Epilepsy , Humans , Cross-Sectional Studies , Epilepsy/epidemiology , Smokers , Risk Factors , Smoking/adverse effects , Smoking/epidemiologyABSTRACT
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis. METHODS: On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS. RESULTS: Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06-1.22, I2=44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03-1.21, I2=49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10-1.49, I2=66%, p<0.001) and AOR of 1.28 (95% CI: 1.10-1.48, I2=58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve. CONCLUSIONS: Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial.TRIAL REGISTRATION: The study was registered in PROSPERO.IDENTIFIER: CRD42023388822.
ABSTRACT
White blood cells (WBCs) act as mediators of inflammatory responses and are commonly measured in hospitals. Although several studies have reported a relation between WBC count and mortality, no systematic review or meta-analysis has been conducted. This study aimed to identify an association between WBC count and mortality. We conducted a systematic search on Embase using keywords such as "white blood cell" and "mortality." We analyzed the hazard ratios (HRs) for WBC count of 1.0 × 109 cells/L regarding 2 criteria: the cause of mortality and the follow-up period. A total of 13 of 222 articles comprising a total of 62,904 participants were included in this study, meeting the criteria set. A positive association was observed between WBC count and mortality, as indicated by an HR of 1.10 (95% confidence interval [CI] 1.08 to 1.13). In additionally, WBC count emerged as a significant predictor of mortality in both groups, with an HR of 1.10 (95% CI 1.07 to 1.12) for patients with cardiovascular disease and an HR of 1.12 (95% CI 1.07 to 1.17) for the general population or patients with COVID-19. Furthermore, a higher WBC count demonstrated a significant association with long-term all-cause mortality (HR 1.09, 95% CI 1.07 to 1.12) and long-term cardiovascular mortality (HR 1.05, 95% CI 1.02 to 1.07). Similarly, a significant association was found between higher WBC count and short-term all-cause mortality (HR 1.12, 95% CI 1.09 to 1.16) and cardiovascular mortality (HR 1.12, 95% CI 1.07 to 1.17). Further research is necessary to explore the relation between WBC count and disease progression or death and to establish causality between elevated WBC count and disease progression.
Subject(s)
COVID-19 , Cardiovascular Diseases , Humans , Prognosis , Leukocyte Count , Disease ProgressionABSTRACT
OBJECTIVES: Despite advances in the maintenance of arteriovenous fistulas (AVFs), the patency rates remain suboptimal. Most AVFs fail due to outflow vein stenosis; however, the underlying mechanism of AVF stenosis remains unclear. The present study aimed to identify key factors associated with AVF outflow stenosis. METHODS: We obtained gene expression profiling data for the outflow vein of AVF from three Gene Expression Omnibus database datasets (GSE39488, GSE97377, and GSE116268) and analyzed the common differentially expressed genes (DEGs). We evaluated a common DEG in an aortocaval mouse model and the stenotic outflow veins of AVFs collected from patients. Furthermore, we isolated vascular smooth muscle cells (VSMCs) from the inferior vena cava (IVC) of wild-type (WT) and osteopontin (Opn)-knockout (KO) mice and assessed the proliferation of VSMCs following stimulation with platelet-derived growth factors (PDGFs). RESULTS: OPN was the only common upregulated DEG among all datasets. OPN was expressed in the medial layer of the outflow vein of AVF in aortocaval mouse models and co-stained with the VSMC marker (α-smooth muscle actin). OPN expression was markedly increased in the VSMCs of stenotic outflow veins of AVF collected from patients undergoing hemodialysis compared to presurgical veins acquired during AVF formation surgery. PDGF-induced VSMC proliferation was significantly increased in the VSMCs isolated from the IVC of WT mice but not in those isolated from the IVC of Opn-KO mice. CONCLUSIONS: OPN may be a key gene involved in VSMC proliferation in the AVF outflow veins and a therapeutic target to improve the AVF patency rate.
Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Mice , Animals , Muscle, Smooth, Vascular/metabolism , Arteriovenous Shunt, Surgical/adverse effects , Osteopontin/genetics , Osteopontin/metabolism , Constriction, Pathologic/metabolism , Platelet-Derived Growth Factor , Cell Proliferation , Arteriovenous Fistula/metabolismABSTRACT
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (GSE28829, GSE43292, GSE100927, and GSE120521), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis.
Subject(s)
Atherosclerosis , Phosphoenolpyruvate Carboxykinase (ATP) , Plaque, Atherosclerotic , Animals , Atherosclerosis/metabolism , Cell Movement , Cell Proliferation/genetics , Cells, Cultured , Disease Models, Animal , Humans , Hyperplasia/metabolism , Hyperplasia/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Neointima/genetics , Neointima/metabolism , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/metabolismABSTRACT
The surgical workforce, like the rest of the population, is ageing. This has raised concerns about the association between the age of the surgeon and their surgical outcomes. We performed a systematic review and meta-analysis of cohort studies on postoperative mortality and major morbidity according to the surgeons' age. The search was performed on February 2021 using the Embase, Medline and CENTRAL databases. Postoperative mortality and major morbidity were evaluated as clinical outcomes. We categorized the surgeons' age into young-, middle-, and old-aged surgeons. We compared the differences in clinical outcomes for younger and older surgeons compared to middle-aged surgeons. Subgroup analyses were performed for major and minor surgery. Ten retrospective cohort studies on 29 various surgeries with 1,666,108 patients were considered. The mortality in patients undergoing surgery by old-aged surgeons was 1.14 (1.02-1.28, p = 0.02) (I2 = 80%) compared to those by middle-aged surgeon. No significant differences were observed according to the surgeon's age in the major morbidity and subgroup analyses. This meta-analysis indicated that surgeries performed by old-aged surgeons had a higher risk of postoperative mortality than those by middle-aged surgeons. Thus, it necessitates the introduction of a multidisciplinary approach to evaluate the performance of senior surgeons.
Subject(s)
Surgeons , Aged , Cohort Studies , Humans , Middle Aged , Morbidity , Postoperative Complications/epidemiology , Retrospective StudiesABSTRACT
BACKGROUND: Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Although a positive association between alcohol consumption and epilepsy has been demonstrated in previous meta-analyses of case-control studies, the results of several recently published large cohort studies are contradictory. Therefore, we conducted an updated meta-analysis that included more recent data to clarify the association between alcohol consumption and epilepsy. METHODS: The search was performed on 25 January 2021 using the Embase and MEDLINE databases. Cohort or case-control studies were eligible for inclusion in this study. We used restricted cubic spline analysis to perform a dose-response meta-analysis. RESULTS: A total of eight studies, including three cohort and five case-control studies, were included in our meta-analysis. The pooled risk of epilepsy was 1.70 (1.16-2.49) in alcohol users compared to non-drinkers. Subgroup analysis of 50 g units showed that the epilepsy risk increased as alcohol intake increased. The pooled risk of cohort studies was 1.00 (0.65-1.54), and the pooled risk of case-control studies was 2.61 (1.29-5.29). According to the dose-response analysis, the regression coefficient was 1.009 (1.004-1.014), indicating a significant positive dose-response relationship. CONCLUSION: Unlike the case-control studies, the cohort studies did not reveal a significant association between alcohol consumption and epilepsy. Further large cohort studies for the general population are required to assert a definite causal relationship between alcohol consumption and epilepsy and to identify a potential threshold.
Subject(s)
Alcohol Drinking , Epilepsy , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Case-Control Studies , Cohort Studies , Epilepsy/epidemiology , Humans , Risk Factors , Seizures/epidemiologyABSTRACT
BACKGROUND: Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed. METHODS: We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay. RESULTS: Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN (pâ=â0.0328), whereas serum SLPI levels did not differ (pâ=â0.9651). CONCLUSION: In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN.
ABSTRACT
PURPOSE: Intensive care unit (ICU) bed availability is key to critical patient care. In many countries, older patients generally account for a significant proportion of hospitalizations and ICU admissions. Therefore, considering the rapidly increasing aging population in South Korea, it is important to establish whether the demand for critical care is currently met by available ICU beds. MATERIALS AND METHODS: We evaluated a 9-year trend in ICU bed supply and ICU length of stay in South Korea between 2011 and 2019 in a population-based cross-sectional analysis, using data from the Korean Health Insurance Review & Assessment Service and Statistics database. We described the changes in ICU bed rates in adult (≥20 years) and older adult (≥65 years) populations. ICU length of stay was categorized similarly and was used to predict future ICU bed demands. RESULTS: The ICU bed rate per 100000 adults increased from 18.5 in 2011 to 19.5 in 2019. In contrast, the ICU bed rate per 100000 older adults decreased from 127.6 in 2011 to 104.0 in 2019. ICU length of stay increased by 43.8% for adults and 55.6% for older adults. In 2019, the regional differences in the ICU bed rate nearly doubled, and the ICU length of stay increased six-fold. The ICU bed occupancy rate in South Korea is expected to rise to 102.7% in 2030. CONCLUSION: The discrepancy between the demand and supply of ICU beds in South Korea requires urgent action to anticipate future ICU demands.
Subject(s)
Bed Occupancy , Intensive Care Units , Aged , Critical Care , Cross-Sectional Studies , Humans , Length of Stay , Republic of KoreaABSTRACT
A recent meta-analysis addressed increased risk of death following revascularization with paclitaxel-coated devices in femopopliteal artery. We evaluated differences in all-cause mortality and amputation free survival between peripheral arterial disease (PAD) patients who were treated with paclitaxel-coated devices and non-paclitaxel-coated devices. This was retrospective population-based cohort study from the National Health Insurance Service claims in South Korea from 2015 to 2019. Multivariate Cox regression analyses after propensity score matching were applied to identify all-cause mortality and amputation-free survival. After propensity score matching, there were 6090 patients per group. The median follow-up days was 580 days (interquartile range [IQR] 240-991 days) and 433 days (IQR 175-757 days) for the non-paclitaxel-coated device group and paclitaxel-coated device group, respectively. Multivariate analysis adjusted for age, sex, diabetes, hypertension, warfarin, and new oral anticoagulants showed that the mortality rate associated with paclitaxel-coated devices was not significantly higher than non-paclitaxel-coated devices (hazard ratio [HR] 0.992; 95% CI 0.91-1.08). The rate of amputation events was higher in patients with paclitaxel-coated devices than those with non-paclitaxel-coated devices (HR 1.614; 95% CI 1.46-1.78). In this analysis, the mortality rate in patients with PAD was not associated with the use of paclitaxel-coated devices, despite a higher amputation rate.
Subject(s)
Angioplasty, Balloon/adverse effects , Paclitaxel/adverse effects , Peripheral Arterial Disease/surgery , Postoperative Complications/mortality , Aged , Aged, 80 and over , Amputation, Surgical/statistics & numerical data , Angioplasty, Balloon/methods , Comorbidity , Female , Humans , Leg , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/surgery , Stents/adverse effectsABSTRACT
BACKGROUND: Ultrasound-guided regional anesthesia has gained popularity over the last decade. This study aimed to assess whether YouTube videos sufficiently serve as an adjunctive tool for learning how to perform an ultrasound-guided brachial plexus block (BPB). METHODS: All YouTube videos were classified, based on their sources, as either academic, manufacturer, educational, or individual videos. The metrics, accuracy, utility, reliability (using the Journal of American Medical Association Score benchmark criteria (JAMAS)), and educational quality (using the Global Quality Score (GQS) and Brachial Plexus Block Specific Quality Score (BSQS)) were validated. RESULTS: Here, 175 videos were included. Academic (1.19 ± 0.62, mean ± standard deviation), manufacturer (1.17 ± 0.71), and educational videos (1.15 ± 0.76) had better JAMAS accuracy and reliability than individual videos (0.26 ± 0.67) (p < 0.001). Manufacturer (11.22 ± 1.63) and educational videos (10.33 ± 3.34) had a higher BSQS than individual videos (7.32 ± 4.20) (p < 0.001). All sources weakly addressed the equipment preparation and post-procedure questions after BSQS analysis. CONCLUSIONS: The reliability and quality of ultrasound-guided BPB videos differ depending on their source. As YouTube is a useful educational platform for learners and teachers, global societies of regional anesthesiologists should set a standard for videos.
ABSTRACT
Opioid prescribing data can guide regulation policy by informing trends and types of opioids prescribed and geographic variations. In South Korea, the nationwide data on prescribing opioids remain unclear. We aimed to evaluate an 11-year trend of opioid prescription in South Korea, both nationally and by administrative districts. A population-based cross-sectional analysis of opioid prescriptions dispensed nationwide in outpatient departments between January 1, 2009, and December 31, 2019, was conducted for this study. Data were obtained from the Health Insurance Review & Assessment Service. The types of opioids prescribed were categorized into total, strong, and extended-release and long-acting formulation. Trends in the prescription rate per 1000 persons were examined over time nationally and across administrative districts. There are significant increasing trends for total, strong, and extended-release and long-acting opioid prescriptions (rate per 1000 persons in 2009 and 2019: total opioids, 347.5 and 531.3; strong opioids, 0.6 and 15.2; extended-release and long-acting opioids, 6.8 and 82.0). The pattern of dispensing opioids increased from 2009 to 2013 and slowed down from 2013 to 2019. The rate of opioid prescriptions issued between administrative districts nearly doubled for all types of opioids. Prescription opioid dispensing increased substantially over the study period. The increase in the prescription of total opioids was largely attributed to an increase in the prescription of weak opioids. However, the increase in prescriptions of extended-release and long-acting opioids could be a future concern. These data may inform government organizations to create regulations and interventions for prescribing opioids.
Subject(s)
Opioid Epidemic/trends , Opioid-Related Disorders/epidemiology , Practice Patterns, Physicians'/trends , Analgesics, Opioid/therapeutic use , Drug Prescriptions/statistics & numerical data , Epidemics/prevention & control , Epidemics/statistics & numerical data , Humans , Republic of KoreaABSTRACT
Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell-cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.
Subject(s)
Aortic Aneurysm, Abdominal/genetics , Blood Vessels/pathology , Intracellular Signaling Peptides and Proteins/genetics , Aged , Animals , Aortic Aneurysm, Abdominal/pathology , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Open Reading Frames , Zebrafish/embryologyABSTRACT
PURPOSE: Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. MATERIALS AND METHODS: We downloaded clinical and genomic data from The Cancer Genome Atlas. We used Kaplan-Meier with a log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. RESULTS: In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistical significance. In the Cox regression, thyroid carcinoma and glioblastoma multiforme and ccRCC showed significant results. Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. CONCLUSION: Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.
Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , Antihypertensive Agents/administration & dosage , COVID-19 Drug Treatment , COVID-19 , Carcinoma, Renal Cell , Gene Expression Regulation, Neoplastic/drug effects , Kidney Neoplasms , Neoplasm Proteins/biosynthesis , COVID-19/metabolism , COVID-19/mortality , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Disease-Free Survival , Female , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Male , Survival RateABSTRACT
BACKGROUND/AIM: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer. MATERIALS AND METHODS: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model. RESULTS: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis. CONCLUSION: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway.
Subject(s)
Biomarkers, Tumor/genetics , Ovarian Neoplasms/genetics , Proteins/genetics , Tumor Suppressor Protein p53/genetics , Aged , Apoptosis/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Gene Knockdown Techniques , Humans , Intercellular Signaling Peptides and Proteins , Middle Aged , Ovarian Neoplasms/pathology , PrognosisABSTRACT
Adolescent idiopathic scoliosis is the most common spinal deformity during puberty, especially in females. It is characterized by aberrant skeletal growth and generalized reduced bone density, which is associated with impaired bone mineral metabolism. Despite recent progress in multidisciplinary research to support various hypotheses, the pathogenesis of Adolescent idiopathic scoliosis is still not clearly understood. One of the hypothesis is to study the role of mesenchymal stem cells due to its involvement in the above-mentioned bone metabolic abnormalities. In this review, we will summarize reported literatures on the role of mesenchymal stem cells, particularly in the pathogenesis of Adolescent idiopathic scoliosis. In addition, we will describe the research on mesenchymal stem cells of Adolescent idiopathic scoliosis performed using bioinformatics tools.
ABSTRACT
BACKGROUND: High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis. METHODS: A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR = 1.61, 95% CI: 1.35-1.92, p < 0.0001) and disease-free survival (DFS) (HR = 1.52, 95% CI: 1.31-2.18, p < 0.001) were observed. In the subgroup analysis for DFS, high cathepsin D was significantly associated with poor prognosis in node-positive patients (HR = 1.38, 95% CI: 1.25-1.71, p < 0.00001), node-negative patients (HR = 1.78, 95% CI: 1.39-2.27, p < 0.0001), early stage patients (HR = 1.73, 95% CI: 1.34-2.23, p < 0.0001), and treated with chemotherapy patients (HR = 1.60, 95% CI: 1.21-2.12, p < 0.001). Interestingly, patients treated with tamoxifen had a low risk of relapse when their cathepsin D levels were high (HR = 0.71, 95% CI: 0.52-0.98, p = 0.04) and a high risk of relapse when their cathepsin D levels were low (HR = 1.50, 95% CI: 1.22-1.85, p = 0.0001). CONCLUSIONS: Our meta-analysis suggests that high expression levels of cathepsin D are associated with a poor prognosis in breast cancer. Based on our subgroup analysis, we believe that cathepsin D can act as a marker for poor breast cancer prognosis and also as a therapeutic target for breast cancer.