Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.7150/ijms.100367
Zheng Wang, Danni Hu, Huzi Xu, Rui Zeng, Ying Yao
Background: Obstructive nephropathy (ON), resulting from hindered urine flow, significantly contributes to both acute kidney injury (AKI) and chronic kidney disease (CKD). Research has consistently highlighted increased lymphatic vessels (LVs) density in diverse kidney diseases. However, the precise involvement of LVs in ON remains unclear. Methods: Patients diagnosed with ON were enrolled in this study from January 2020 to December 2023. LVs and histological pathology in renal biopsy tissues were detected through immunohistochemistry and Periodic Acid-Schiff staining. Patients were categorized into two cohorts based on their estimated glomerular filtration rate (eGFR) levels: one cohort included patients with eGFR < 90, while the other encompassed those with eGFR ≥ 90. Univariate and multivariable logistic regression analyses were conducted to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between the two cohorts. Results: 239 patients were enrolled in the study. The density of LVs was elevated in ON, with even higher densities observed in patients with severe renal impairment. Additionally, several risk factors contributing to the deterioration of renal function in ON patients have been identified, including age, ureteral calculi (UC), alanine aminotransferase (ALT), and uric acid (UA). Furthermore, by leveraging LVs density, multiple robust models have been established to predict severe renal impairment in ON. Conclusions: Lymphatic vessels density is significantly elevated in ON, serving as an independent risk factor for the decline in renal function.
背景:尿流受阻导致的阻塞性肾病(ON)是急性肾损伤(AKI)和慢性肾病(CKD)的重要诱因。研究一直强调各种肾脏疾病中淋巴管(LV)密度的增加。然而,淋巴管在肾损伤中的确切参与程度仍不清楚。研究方法本研究从 2020 年 1 月至 2023 年 12 月招募了被诊断为 ON 的患者。通过免疫组化和高碘酸-Schiff染色检测肾活检组织中的LVs和组织病理学。根据患者的估计肾小球滤过率(eGFR)水平将其分为两组:一组包括eGFR<90的患者,另一组包括eGFR≥90的患者。我们进行了单变量和多变量逻辑回归分析,以确定两个队列之间相关性的几率比(OR)和 95% 的置信区间(CI)。结果:239 名患者参与了研究。ON 患者的左心室密度升高,严重肾功能损害患者的左心室密度甚至更高。此外,还发现了导致 ON 患者肾功能恶化的几个风险因素,包括年龄、输尿管结石(UC)、丙氨酸氨基转移酶(ALT)和尿酸(UA)。此外,通过利用左心室密度,还建立了多个稳健的模型来预测 ON 患者的严重肾功能损害。结论淋巴管密度在登革热患者中明显升高,是肾功能下降的独立风险因素。
{"title":"Increased Lymphatic Vessels: A Risk Factor for Severe Renal Function Loss in Obstructive Nephropathy Patients.","authors":"Zheng Wang, Danni Hu, Huzi Xu, Rui Zeng, Ying Yao","doi":"10.7150/ijms.100367","DOIUrl":"10.7150/ijms.100367","url":null,"abstract":"<p><p><b>Background:</b> Obstructive nephropathy (ON), resulting from hindered urine flow, significantly contributes to both acute kidney injury (AKI) and chronic kidney disease (CKD). Research has consistently highlighted increased lymphatic vessels (LVs) density in diverse kidney diseases. However, the precise involvement of LVs in ON remains unclear. <b>Methods:</b> Patients diagnosed with ON were enrolled in this study from January 2020 to December 2023. LVs and histological pathology in renal biopsy tissues were detected through immunohistochemistry and Periodic Acid-Schiff staining. Patients were categorized into two cohorts based on their estimated glomerular filtration rate (eGFR) levels: one cohort included patients with eGFR < 90, while the other encompassed those with eGFR ≥ 90. Univariate and multivariable logistic regression analyses were conducted to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between the two cohorts. <b>Results:</b> 239 patients were enrolled in the study. The density of LVs was elevated in ON, with even higher densities observed in patients with severe renal impairment. Additionally, several risk factors contributing to the deterioration of renal function in ON patients have been identified, including age, ureteral calculi (UC), alanine aminotransferase (ALT), and uric acid (UA). Furthermore, by leveraging LVs density, multiple robust models have been established to predict severe renal impairment in ON. <b>Conclusions:</b> Lymphatic vessels density is significantly elevated in ON, serving as an independent risk factor for the decline in renal function.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.7150/ijms.99236
Khaled Sayar, Abdullah Bamosa, Lubna Al-Asoom, Ayad Mohammed Salem, Qassim Muaidi
Objectives: In this study, we aimed to assess the maximal oxygen uptake (VO2max) of young, healthy, non-athletic Saudi men using maximum graded exercise with instant breath-by-breath analysis and to compare this value to the predicted VO2max by international formulae. Methods: In this cross-sectional study, 88 young non-athletic normal-weight Saudi subjects were recruited from Eastern Province of Saudi Arabia with mean age (21.3 ± 1.5 years), weight: (64.7 ± 7.5 kg), height: (172.3 ± 6.1 cm) and body mass index: (21.8 ± 2.1). All subjects were interviewed and examined for eligibility, after which they performed maximum graded exercise testing on a treadmill to obtain VO2max. The predicted VO2max was also generated using the following formulae (Edvardsen, Fairbarns, FRIENDS, Hansen, and Jones). Results: The mean measured VO2max was 41.9 ± 7.2 ml/kg/min. While the predicted VO2max using the formulae were: Edvardsen = 66.8 ± 7.9, Fairbarns = 64.1 ± 4.7, FRIENDS = 53.5 ± 2.2, Hansen = 42.8 ± 0.54, and Jones = 50.9 ± 5.1 ml/kg/min. There was a significant difference between all the predicted VO2max and the measured one using the paired t-test (P < 0.001), except for the Hansen's predicted value (P = 0.212). The effect size index (Cohen's d) for the comparison of Hansen's VO2max and measured VO2max was trivial and equal to 0.13. The Bland-Altman test showed good agreement between the measured and Hansen's predicted VO2max. Conclusion: This study demonstrated the mean VO2max value of young, healthy, and non-athletic Saudi men. This value was lower than Western values, which might be due to low physical activity or racial differences. Most international formulae overestimate the VO2max in this population, except for the Hansen equation. Therefore, Hansen's predicted VO2max might be the best available reference value for the diagnosis and prognosis of young Saudi individuals undergoing maximum exercise testing.
{"title":"Validation of VO<sub>2max</sub> Prediction Using International Formulae for Young Saudi Men.","authors":"Khaled Sayar, Abdullah Bamosa, Lubna Al-Asoom, Ayad Mohammed Salem, Qassim Muaidi","doi":"10.7150/ijms.99236","DOIUrl":"10.7150/ijms.99236","url":null,"abstract":"<p><p><b>Objectives:</b> In this study, we aimed to assess the maximal oxygen uptake (VO<sub>2max</sub>) of young, healthy, non-athletic Saudi men using maximum graded exercise with instant breath-by-breath analysis and to compare this value to the predicted VO<sub>2max</sub> by international formulae. <b>Methods:</b> In this cross-sectional study, 88 young non-athletic normal-weight Saudi subjects were recruited from Eastern Province of Saudi Arabia with mean age (21.3 ± 1.5 years), weight: (64.7 ± 7.5 kg), height: (172.3 ± 6.1 cm) and body mass index: (21.8 ± 2.1). All subjects were interviewed and examined for eligibility, after which they performed maximum graded exercise testing on a treadmill to obtain VO<sub>2max</sub>. The predicted VO<sub>2max</sub> was also generated using the following formulae (Edvardsen, Fairbarns, FRIENDS, Hansen, and Jones). <b>Results:</b> The mean measured VO<sub>2max</sub> was 41.9 ± 7.2 ml/kg/min. While the predicted VO<sub>2max</sub> using the formulae were: Edvardsen = 66.8 ± 7.9, Fairbarns = 64.1 ± 4.7, FRIENDS = 53.5 ± 2.2, Hansen = 42.8 ± 0.54, and Jones = 50.9 ± 5.1 ml/kg/min. There was a significant difference between all the predicted VO<sub>2max</sub> and the measured one using the paired t-test (P < 0.001), except for the Hansen's predicted value (P = 0.212). The effect size index (Cohen's d) for the comparison of Hansen's VO<sub>2max</sub> and measured VO<sub>2max</sub> was trivial and equal to 0.13. The Bland-Altman test showed good agreement between the measured and Hansen's predicted VO<sub>2max</sub>. <b>Conclusion:</b> This study demonstrated the mean VO<sub>2max</sub> value of young, healthy, and non-athletic Saudi men. This value was lower than Western values, which might be due to low physical activity or racial differences. Most international formulae overestimate the VO<sub>2max</sub> in this population, except for the Hansen equation. Therefore, Hansen's predicted VO<sub>2max</sub> might be the best available reference value for the diagnosis and prognosis of young Saudi individuals undergoing maximum exercise testing.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.7150/ijms.97404
Yin-Han Liao, Li Chen, Bing-Hua Feng, Wei Lv, Xuan-Ping Huang, Hao Li, Cui-Ping Li
Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.
{"title":"Revelation of comprehensive cell profiling of primary and metastatic tumour ecosystems in oral squamous cell carcinoma by single-cell transcriptomic analysis.","authors":"Yin-Han Liao, Li Chen, Bing-Hua Feng, Wei Lv, Xuan-Ping Huang, Hao Li, Cui-Ping Li","doi":"10.7150/ijms.97404","DOIUrl":"10.7150/ijms.97404","url":null,"abstract":"<p><p><b>Background:</b> The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. <b>Methods:</b> Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. <b>Results:</b> A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. <b>Conclusions:</b> The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-01-01DOI: 10.7150/ijms.99992
Guangyang Cheng, Zhaokai Zhou, Shiqi Li, Zhuo Ye, Yan Wang, Jianguo Wen, Chuanchuan Ren
Background: Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. Methods: The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). Results: The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. Conclusion: In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities.
背景:在了解癌症相关生物学过程或分子功能的研究中,蛋白质信息往往被 RNA 数据所取代,而对肾透明细胞癌(KIRC)预后有重要意义的蛋白质仍有待挖掘。研究方法利用癌症基因组图谱计划(TCGA)数据筛选对肾透明细胞癌(KIRC)有预后意义的蛋白质。利用机器学习算法建立蛋白质预后模型。此外,还分析了不同蛋白质风险亚组的免疫浸润丰度、体细胞突变差异和免疫治疗反应。最后,利用在线数据库和定量实时 PCR(qRT-PCR)对蛋白编码基因进行了验证。结果:根据预后蛋白将患者分为两个风险类别,并观察到两组患者的总生存期(OS)和无进展间期(PFI)存在显著差异。高风险组的 OS 更差,两组患者的免疫浸润程度也有显著差异。此外,提名图在预测 KIRC 患者的生存率方面显示出较高的准确性。结论在这项研究中,我们从生存预测、免疫治疗反应、体细胞突变和免疫微环境等方面阐明了与预后相关的核心蛋白。此外,我们还建立了一个具有出色预测能力的可靠预后模型。
{"title":"Integration of proteomics and transcriptomics to construct a prognostic signature of renal clear cell carcinoma.","authors":"Guangyang Cheng, Zhaokai Zhou, Shiqi Li, Zhuo Ye, Yan Wang, Jianguo Wen, Chuanchuan Ren","doi":"10.7150/ijms.99992","DOIUrl":"10.7150/ijms.99992","url":null,"abstract":"<p><p><b>Background:</b> Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. <b>Methods:</b> The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). <b>Results:</b> The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. <b>Conclusion:</b> In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-01-01DOI: 10.7150/ijms.97051
Nan Wang, Muhui Lin, Wanshu Guo, Yunpeng Cao
Purpose: Cognitive dysfunction caused by chronic cerebral hypoperfusion (CCH) is the leading cause of vascular dementia. Therefore, it is necessary to explore the mechanism that causes cerebral injury and find an effective therapy. Methods: Bone marrow mononuclear cells (BMMNCs) were extracted to detect the activity by CCK-8 kit and verify the transfection efficiency using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). A CCH rat model was established. Superparamagnetic iron oxide nanoparticles (BMPs)-PEI-Slit2/BMMNCs were injected into the tail vein and intervened with an external magnetic field. Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The Slit/Robo pathway-related proteins Slit2 and Robo4 were detected by RT-qPCR and Western blotting. Results: The neurological score of the CCH group significantly increased compared with that of the sham group (P<0.05). The levels of brain injury markers S-100β and NSE were significantly higher in the CCH group than in the sham group (P<0.05). Neuronal apoptosis in the frontal cortex and hippocampus of CCH rats significantly increased compared with that of the sham group (P<0.05). The expression levels of Slit2 and Robo4 mRNAs and proteins in brain tissue of CCH rats significantly increased (P<0.05). The neurological function scores of CCH rats treated with BMP-PEI-Slit2/BMMNC significantly increased after Robo4 siRNA administration (P<0.05). Conclusion: BMP combination with the CCH-related gene Slit2 can effectively improve the efficiency of BMMNC transplantation in treatment.
{"title":"Magnetic nanomagnetic nanoparticles combining with Slit2 gene and bone marrow mononuclear cells to improve cognitive dysfunction in rats with chronic cerebral ischemia.","authors":"Nan Wang, Muhui Lin, Wanshu Guo, Yunpeng Cao","doi":"10.7150/ijms.97051","DOIUrl":"10.7150/ijms.97051","url":null,"abstract":"<p><p><b>Purpose:</b> Cognitive dysfunction caused by chronic cerebral hypoperfusion (CCH) is the leading cause of vascular dementia. Therefore, it is necessary to explore the mechanism that causes cerebral injury and find an effective therapy. <b>Methods:</b> Bone marrow mononuclear cells (BMMNCs) were extracted to detect the activity by CCK-8 kit and verify the transfection efficiency using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). A CCH rat model was established. Superparamagnetic iron oxide nanoparticles (BMPs)-PEI-Slit2/BMMNCs were injected into the tail vein and intervened with an external magnetic field. Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The Slit/Robo pathway-related proteins Slit2 and Robo4 were detected by RT-qPCR and Western blotting. <b>Results:</b> The neurological score of the CCH group significantly increased compared with that of the sham group (P<0.05). The levels of brain injury markers S-100β and NSE were significantly higher in the CCH group than in the sham group (P<0.05). Neuronal apoptosis in the frontal cortex and hippocampus of CCH rats significantly increased compared with that of the sham group (P<0.05). The expression levels of Slit2 and Robo4 mRNAs and proteins in brain tissue of CCH rats significantly increased (P<0.05). The neurological function scores of CCH rats treated with BMP-PEI-Slit2/BMMNC significantly increased after Robo4 siRNA administration (P<0.05). <b>Conclusion:</b> BMP combination with the CCH-related gene Slit2 can effectively improve the efficiency of BMMNC transplantation in treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Osteoporosis is a prevalent skeletal disorder influenced by age, hormonal changes, medication use, nutrition, and genetics. The relationship between MTHFR and osteoporosis remains unclear, especially in Asians. The aim of our study was to elucidate the impact of MTHFR on osteoporosis and fracture risk. Materials and Methods: Participants were recruited from the Taiwan Precision Medicine Initiative at Taichung Veterans General Hospital. A total of 3,503 subjects with available bone mineral density measurements were selected. Using the Axiom Genome-Wide TWB 2.0 Array, we identified the MTHFR rs1801133 variant. Among these subjects, 1,624 patients carrying the variant were included in the case group, while the remaining 1,879 patients without the variant served as the control group. Results: Overall, individuals carrying the MTHFR rs1801133 variant exhibited a significantly elevated risk of developing osteoporosis. Stratified analysis by different genotypes, the results revealed a statistically significant association between the heterozygous genotype of MTHFR rs1801133 and osteoporosis. However, there was no significant correlation between MTHFR genotypes and fracture risk. Furthermore, subgroup analysis of female patients revealed age, a known risk factor, was associated with both osteoporosis and fractures. Interestingly, the presence of the MTHFR rs1801133 variant did not confer an increased risk of osteoporosis or fractures in females. Conclusion: Our study revealed a notable increase in the prevalence of osteoporosis among individuals carrying the MTHFR rs1801133 variant. Nevertheless, these individuals did not exhibit a heightened risk of major or hip fractures compared to non-carriers. Our findings could be of value in raising awareness of the increased risk of osteoporosis among individuals with this genetic variant.
{"title":"Association of Methylenetetrahydrofolate Reductase rs1801133 Polymorphism with osteoporosis and fracture risk in Taiwan.","authors":"Meng-Hua Li, I-Chieh Chen, Hui-Wen Yang, Hsin-Chien Yen, Yu-Yuan Ke, Yi-Ming Chen, Chia-Chi Hsu","doi":"10.7150/ijms.97524","DOIUrl":"10.7150/ijms.97524","url":null,"abstract":"<p><p><b>Introduction:</b> Osteoporosis is a prevalent skeletal disorder influenced by age, hormonal changes, medication use, nutrition, and genetics. The relationship between MTHFR and osteoporosis remains unclear, especially in Asians. The aim of our study was to elucidate the impact of MTHFR on osteoporosis and fracture risk. <b>Materials and Methods:</b> Participants were recruited from the Taiwan Precision Medicine Initiative at Taichung Veterans General Hospital. A total of 3,503 subjects with available bone mineral density measurements were selected. Using the Axiom Genome-Wide TWB 2.0 Array, we identified the MTHFR rs1801133 variant. Among these subjects, 1,624 patients carrying the variant were included in the case group, while the remaining 1,879 patients without the variant served as the control group. <b>Results:</b> Overall, individuals carrying the MTHFR rs1801133 variant exhibited a significantly elevated risk of developing osteoporosis. Stratified analysis by different genotypes, the results revealed a statistically significant association between the heterozygous genotype of MTHFR rs1801133 and osteoporosis. However, there was no significant correlation between MTHFR genotypes and fracture risk. Furthermore, subgroup analysis of female patients revealed age, a known risk factor, was associated with both osteoporosis and fractures. Interestingly, the presence of the MTHFR rs1801133 variant did not confer an increased risk of osteoporosis or fractures in females. <b>Conclusion:</b> Our study revealed a notable increase in the prevalence of osteoporosis among individuals carrying the MTHFR rs1801133 variant. Nevertheless, these individuals did not exhibit a heightened risk of major or hip fractures compared to non-carriers. Our findings could be of value in raising awareness of the increased risk of osteoporosis among individuals with this genetic variant.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Total knee replacement (TKR) is a common surgical procedure for osteoarthritis (OA) patients. TKR may increase susceptibility to herpes zoster (HZ) by inducing immunosuppression, surgical stress, and nerve injury. However, limited data exist on the relationship between TKR and HZ. This study examined the risk of HZ over time among OA patients who underwent TKR and those who did not, using a large population-based cohort. Method: Utilizing the TriNetX research network, people with OA and underwent TKR were recruited as case group. After 1:1 propensity score matching, OA patients who never experienced TKR were included as control group. Covariates, including demographics, comorbidities, and laboratory data, were balanced using propensity score matching. A 5-year follow-up assessed the hazard ratio of incident HZ and related complications. Results: Compared to the control group, a significantly elevated risk of HZ was observed in the TKR cohort across 5-year follow-up period, with the hazard ratio of 1.223 (95% CI: 1.089-1.373). Zoster without complications presented 1.173-fold risk in TKR patients while comparing with non-TKR controls. However, most other secondary outcomes related to HZ complications-such as encephalitis, neurological involvement, ocular disease, and disseminated zoster-did not show a significant increase in risk. The risk of HZ was statistically significant for females and older adults in the TKR cohort than in the control cohort. Conclusions: OA patients who underwent TKR had an increased risk of HZ compared to those who did not receive the procedure, especially females and older adults. These findings highlight the need for HZ monitoring/prevention protocols and further research on mitigating viral reactivation after major joint surgery.
{"title":"Herpes Zoster Risk After Total Knee Replacement: a multicenter, propensity-score-matched cohort study in the United States.","authors":"Wen-Chieh Liao, Shao-Wei Lo, Chih-Lung Wu, Sin-Ei Juang, Hui-Chin Chang, Shuo-Yan Gau, Chen-Pi Li","doi":"10.7150/ijms.97654","DOIUrl":"10.7150/ijms.97654","url":null,"abstract":"<p><p><b>Background:</b> Total knee replacement (TKR) is a common surgical procedure for osteoarthritis (OA) patients. TKR may increase susceptibility to herpes zoster (HZ) by inducing immunosuppression, surgical stress, and nerve injury. However, limited data exist on the relationship between TKR and HZ. This study examined the risk of HZ over time among OA patients who underwent TKR and those who did not, using a large population-based cohort. <b>Method:</b> Utilizing the TriNetX research network, people with OA and underwent TKR were recruited as case group. After 1:1 propensity score matching, OA patients who never experienced TKR were included as control group. Covariates, including demographics, comorbidities, and laboratory data, were balanced using propensity score matching. A 5-year follow-up assessed the hazard ratio of incident HZ and related complications. <b>Results:</b> Compared to the control group, a significantly elevated risk of HZ was observed in the TKR cohort across 5-year follow-up period, with the hazard ratio of 1.223 (95% CI: 1.089-1.373). Zoster without complications presented 1.173-fold risk in TKR patients while comparing with non-TKR controls. However, most other secondary outcomes related to HZ complications-such as encephalitis, neurological involvement, ocular disease, and disseminated zoster-did not show a significant increase in risk. The risk of HZ was statistically significant for females and older adults in the TKR cohort than in the control cohort. <b>Conclusions:</b> OA patients who underwent TKR had an increased risk of HZ compared to those who did not receive the procedure, especially females and older adults. These findings highlight the need for HZ monitoring/prevention protocols and further research on mitigating viral reactivation after major joint surgery.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The early detection of arteriovenous (AV) access dysfunction is crucial for maintaining the patency of vascular access. This study aimed to use deep learning to predict AV access malfunction necessitating further vascular management. Methods: This prospective cohort study enrolled prevalent hemodialysis (HD) patients with an AV fistula or AV graft from a single HD center. Their AV access bruit sounds were recorded weekly using an electronic stethoscope from three different sites (arterial needle site, venous needle site, and the midpoint between the arterial and venous needle sites) before HD sessions. The audio signals were converted to Mel spectrograms using Fourier transformation and utilized to develop deep learning models. Three deep learning models, (1) Convolutional Neural Network (CNN), (2) Convolutional Recurrent Neural Network (CRNN), and (3) Vision Transformers-Gate Recurrent Unit (ViT-GRU), were trained and compared to predict the likelihood of dysfunctional AV access. Results: Total 437 audio recordings were obtained from 84 patients. The CNN model outperformed the other models in the test set, with an F1 score of 0.7037 and area under the receiver operating characteristic curve (AUROC) of 0.7112. The Vit-GRU model had high performance in out-of-fold predictions, with an F1 score of 0.7131 and AUROC of 0.7745, but low generalization ability in the test set, with an F1 score of 0.5225 and AUROC of 0.5977. Conclusions: The CNN model based on Mel spectrograms could predict malfunctioning AV access requiring vascular intervention within 10 days. This approach could serve as a useful screening tool for high-risk AV access.
{"title":"Prediction of Arteriovenous Access Dysfunction by Mel Spectrogram-based Deep Learning Model.","authors":"Tung-Ling Chung, Yi-Hsueh Liu, Pei-Yu Wu, Jiun-Chi Huang, Yi-Chun Tsai, Yu-Chen Wang, Shan-Pin Pan, Ya-Ling Hsu, Szu-Chia Chen","doi":"10.7150/ijms.98421","DOIUrl":"10.7150/ijms.98421","url":null,"abstract":"<p><p><b>Background:</b> The early detection of arteriovenous (AV) access dysfunction is crucial for maintaining the patency of vascular access. This study aimed to use deep learning to predict AV access malfunction necessitating further vascular management. <b>Methods:</b> This prospective cohort study enrolled prevalent hemodialysis (HD) patients with an AV fistula or AV graft from a single HD center. Their AV access bruit sounds were recorded weekly using an electronic stethoscope from three different sites (arterial needle site, venous needle site, and the midpoint between the arterial and venous needle sites) before HD sessions. The audio signals were converted to Mel spectrograms using Fourier transformation and utilized to develop deep learning models. Three deep learning models, (1) Convolutional Neural Network (CNN), (2) Convolutional Recurrent Neural Network (CRNN), and (3) Vision Transformers-Gate Recurrent Unit (ViT-GRU), were trained and compared to predict the likelihood of dysfunctional AV access. <b>Results</b>: Total 437 audio recordings were obtained from 84 patients. The CNN model outperformed the other models in the test set, with an F1 score of 0.7037 and area under the receiver operating characteristic curve (AUROC) of 0.7112. The Vit-GRU model had high performance in out-of-fold predictions, with an F1 score of 0.7131 and AUROC of 0.7745, but low generalization ability in the test set, with an F1 score of 0.5225 and AUROC of 0.5977. <b>Conclusions:</b> The CNN model based on Mel spectrograms could predict malfunctioning AV access requiring vascular intervention within 10 days. This approach could serve as a useful screening tool for high-risk AV access.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyperbaric oxygen (HBO) therapy can attenuate neurological impairment after traumatic brain injury (TBI) and alleviate intestinal dysfunction. However, the role and mechanism of HBO therapy in intestinal dysfunction following TBI remain unclear. Herein, by establishing a mouse model of controlled cortical impact (CCI), we found that HBO therapy reduced histopathological lesions and decreased the levels of inflammatory and oedema proteins in the intestinal tissues of mice 10 days after TBI. We also showed that HBO therapy improved microbiome abundance and probiotic (particularly g_Bifidobacterium) colonisation in mice post-CCI. Then, we identified that the m6A level imcreased notably in injured cortical tissue of CCI+HBO group compared with the CCI group following CCI. Thus, our results suggested that HBO therapy could alleviate TBI-induced intestinal dysfunction and m6A might participate in this regulation process, which provides new insights for exploring the specific mechanism and targets of HBO in the treatment of intestinal dysfunction after TBI, thereby improving the therapeutic effect of HBO.
{"title":"Hyperbaric oxygen therapy alleviates intestinal dysfunction following traumatic brain injury via m<sup>6</sup>A regulation.","authors":"Xuelai Yu, Wei Zhao, Yunyun Liu, Jingchuan Lv, Xiang Zhong, Peizan Huang","doi":"10.7150/ijms.97682","DOIUrl":"10.7150/ijms.97682","url":null,"abstract":"<p><p>Hyperbaric oxygen (HBO) therapy can attenuate neurological impairment after traumatic brain injury (TBI) and alleviate intestinal dysfunction. However, the role and mechanism of HBO therapy in intestinal dysfunction following TBI remain unclear. Herein, by establishing a mouse model of controlled cortical impact (CCI), we found that HBO therapy reduced histopathological lesions and decreased the levels of inflammatory and oedema proteins in the intestinal tissues of mice 10 days after TBI. We also showed that HBO therapy improved microbiome abundance and probiotic (particularly <i>g_Bifidobacterium</i>) colonisation in mice post-CCI. Then, we identified that the m<sup>6</sup>A level imcreased notably in injured cortical tissue of CCI+HBO group compared with the CCI group following CCI. Thus, our results suggested that HBO therapy could alleviate TBI-induced intestinal dysfunction and m<sup>6</sup>A might participate in this regulation process, which provides new insights for exploring the specific mechanism and targets of HBO in the treatment of intestinal dysfunction after TBI, thereby improving the therapeutic effect of HBO.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13eCollection Date: 2024-01-01DOI: 10.7150/ijms.100127
Yehai Li, Min Zhang, Jinchuan Lin, Hang Guo, Hao Zhou, Yong Jin, Zhao Yang
In the realm of this study, obtaining a comprehensive understanding of ischemic brain injury and its molecular foundations is of paramount importance. Our study delved into single-cell data analysis, with a specific focus on sub-celltypes and differentially expressed genes in the aftermath of ischemic injury. Notably, we observed a significant enrichment of the "ATP METABOLIC PROCESS" and "ATP HYDROLYSIS ACTIVITY" pathways, featuring pivotal genes such as Pbx3, Dguok, and Kif21b. A remarkable finding was the consistent upregulation of genes like Fabp7 and Bcl11a within the MCAO group, highlighting their crucial roles in regulating the pathway of mitochondrial ATP synthesis coupled proton transport. Furthermore, our network analysis unveiled pathways like "Neuron differentiation" and "T cell differentiation" as central in the regulatory processes of sub-celltypes. These findings provide valuable insights into the intricate molecular responses and regulatory mechanisms that govern brain injury. The shared differentially expressed genes among sub-celltypes emphasize their significance in orchestrating responses post-ischemic injury. Our research, viewed from the perspective of a medical researcher, contributes to the evolving understanding of the molecular landscape underlying ischemic brain injury, potentially paving the way for targeted therapeutic strategies and improved patient outcomes.
{"title":"Mitochondrial ATP Synthesis and Proton Transport Synergistically Mitigate Oligodendrocyte Progenitor Cell Dysfunction Following Transient Middle Cerebral Artery Occlusion via the Pbx3/Dguok/Kif21b Signaling Pathway.","authors":"Yehai Li, Min Zhang, Jinchuan Lin, Hang Guo, Hao Zhou, Yong Jin, Zhao Yang","doi":"10.7150/ijms.100127","DOIUrl":"10.7150/ijms.100127","url":null,"abstract":"<p><p>In the realm of this study, obtaining a comprehensive understanding of ischemic brain injury and its molecular foundations is of paramount importance. Our study delved into single-cell data analysis, with a specific focus on sub-celltypes and differentially expressed genes in the aftermath of ischemic injury. Notably, we observed a significant enrichment of the \"ATP METABOLIC PROCESS\" and \"ATP HYDROLYSIS ACTIVITY\" pathways, featuring pivotal genes such as Pbx3, Dguok, and Kif21b. A remarkable finding was the consistent upregulation of genes like Fabp7 and Bcl11a within the MCAO group, highlighting their crucial roles in regulating the pathway of mitochondrial ATP synthesis coupled proton transport. Furthermore, our network analysis unveiled pathways like \"Neuron differentiation\" and \"T cell differentiation\" as central in the regulatory processes of sub-celltypes. These findings provide valuable insights into the intricate molecular responses and regulatory mechanisms that govern brain injury. The shared differentially expressed genes among sub-celltypes emphasize their significance in orchestrating responses post-ischemic injury. Our research, viewed from the perspective of a medical researcher, contributes to the evolving understanding of the molecular landscape underlying ischemic brain injury, potentially paving the way for targeted therapeutic strategies and improved patient outcomes.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}