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1.
J Chin Med Assoc ; 87(5): 558-566, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38451103

ABSTRACT

BACKGROUND: According to the theory of traditional Chinese medicine (TCM), all types of body constitutions, except for the Gentleness (ie, the control group in our study), have disease susceptibility and affect the disease development process. This study attempted to investigate the relationship between TCM body constitutions and irritable bowel syndrome (IBS). METHODS: This cross-sectional study was based on Taiwan Biobank (TWB) and collected clinical data from 13 941 subjects aged 30 to 70. The results of the study showed that subjects with Yang-deficiency (N = 3161 subjects, odds ratio [OR] = 2.654, 95% CI = 1.740-3.910), Ying-deficiency (N = 3331 subjects, OR = 1.096, 95% CI = 0.627-1.782) or Stasis (N = 2335 subjects, OR = 1.680, 95% CI = 0.654-3.520) were more likely to have IBS. RESULTS: If the subjects with two or more TCM body constitutions: Yang-deficiency + Ying-deficiency (OR = 3.948, 95% CI = 2.742-5.560), Yang-deficiency + Stasis (OR = 2.312, 95% CI = 1.170-4.112), Ying-deficiency + Stasis (OR = 1.851, 95% CI = 0.828-3.567), or Yang-deficiency + Ying-deficiency + Stasis (OR = 3.826, 95% CI = 2.954-4.932) were also prone to IBS. CONCLUSION: These results confirmed the high correlation between TCM body constitutions and IBS. Because the current treatment for IBS is not entirely satisfactory, integrated traditional Chinese and Western medicine might provide patients with an alternative treatment option to alleviate IBS.


Subject(s)
Irritable Bowel Syndrome , Medicine, Chinese Traditional , Humans , Irritable Bowel Syndrome/drug therapy , Middle Aged , Female , Cross-Sectional Studies , Male , Adult , Aged , Yang Deficiency/drug therapy , Body Constitution , Yin Deficiency
2.
J Chin Med Assoc ; 87(3): 267-272, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38277620

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.


Subject(s)
Induced Pluripotent Stem Cells , Mesenchymal Stem Cells , Cell Differentiation
3.
J Chin Med Assoc ; 87(2): 163-170, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38132887

ABSTRACT

BACKGROUND: The potential of induced pluripotent stem cells (iPSCs) in revolutionizing regenerative medicine cannot be overstated. iPSCs offer a profound opportunity for therapies involving cell replacement, disease modeling, and cell transplantation. However, the widespread application of iPSC cellular therapy faces hurdles, including the imperative to regulate iPSC differentiation rigorously and the inherent genetic disparities among individuals. To address these challenges, the concept of iPSC super donors emerges, holding exceptional genetic attributes and advantageous traits. These super donors serve as a wellspring of standardized, high-quality cell sources, mitigating inter-individual variations and augmenting the efficacy of therapy. METHODS: In pursuit of this goal, our study embarked on the establishment of iPSC cell lines specifically sourced from donors possessing the HLA type (A33:03-B58:01-DRB1*03:01). The reprogramming process was meticulously executed, resulting in the successful generation of iPSC lines from these carefully selected donors. Subsequently, an extensive characterization was conducted to comprehensively understand the features and attributes of these iPSC lines. RESULTS: The outcomes of our research were highly promising. The reprogramming efforts culminated in the generation of iPSC lines from donors with the specified HLA type. These iPSC lines displayed a range of distinctive characteristics that were thoroughly examined and documented. This successful generation of iPSC lines from super donors possessing advantageous genetic traits represents a significant stride towards the realization of their potential in therapeutic applications. CONCLUSION: In summary, our study marks a crucial milestone in the realm of regenerative medicine. The establishment of iPSC lines from super donors with specific HLA types signifies a paradigm shift in addressing challenges related to iPSC cellular therapy. The standardized and high-quality cell sources derived from these super donors hold immense potential for various therapeutic applications. As we move forward, these findings provide a solid foundation for further research and development, ultimately propelling the field of regenerative medicine toward new horizons of efficacy and accessibility.


Subject(s)
Induced Pluripotent Stem Cells , Humans , Cellular Reprogramming , Cell Differentiation , Cell- and Tissue-Based Therapy
4.
Healthcare (Basel) ; 11(21)2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37957996

ABSTRACT

BACKGROUND: In situ simulation is the practice of using simulated scenarios to improve skill implementation, train critical thinking and problem-solving abilities, and enhance self-efficacy. This study aimed to enhance nursing knowledge, skills, and attitudes toward clinical work by applying in situ simulation training to improve the healthcare of critically ill patients. METHODS: This study was conducted from a medical center in northern Taiwan and included 86 trainees who received intensive care training courses from 1 June 2017 to 31 May 2019. The self-report knowledge assessment, empathetic self-efficacy scale, skill assessment, and attitudes of instructors before and after training were collected. The statistical analysis used the Wilcoxon test for knowledge and attitudes, and chi-square tests were used for skills to evaluate the learning effect. RESULTS: The results showed a statistically significant improvement in knowledge, skills, attitudes, and empathy in nursing care. CONCLUSIONS: In situ simulation learning can be an accepted method for nursing skills in the intensive care unit. Through this study, we understood that the in situ simulation method was beneficial to nurses' care and care thinking processes. It is worth developing and evaluating integrated simulation education to enhance learning, change behavior, and promote holistic care in the nursing field.

5.
J Chin Med Assoc ; 86(11): 950-959, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37801590

ABSTRACT

With the discovery of new biomarkers for the early detection of acute myocardial infarction (AMI), advancements in valid medication, and percutaneous coronary intervention (PCI), the overall prognosis of AMI has improved remarkably. Nevertheless, challenges remain which require more difficult work to overcome. Novel diagnostic and therapeutic techniques include new AMI biomarkers, hypothermia therapy, supersaturated oxygen (SSO 2 ) therapy, targeted anti-inflammatory therapy, targeted angiogenesis therapy, and stem cell therapy. With these novel methods, we believe that the infarction size after AMI will decrease, and myocardial injury-associated ventricular remodeling may be avoided. This review focuses on novel advances in the diagnosis and management of AMI.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Prognosis , Biomarkers , Treatment Outcome
6.
J Chin Med Assoc ; 86(11): 966-974, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37683135

ABSTRACT

BACKGROUND: Real-time and appropriate antigen tests play a pivotal role in preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, a previous meta-analysis reported that the antigen test had lower sensitivity for the detection of SARS-CoV-2 in children. To provide a comprehensive evaluation of diagnostic efficiency, we performed an updated meta-analysis to assess the detection accuracy of SARS-CoV-2 antigen tests stratified by days after symptom onset and specimen type in children and adolescents. METHODS: We comprehensively searched for appropriate studies in the PubMed, Embase, and Cochrane Library databases. Studies on the diagnostic accuracy of antigen tests for SARS-CoV-2 in children and adolescents were included. The relevant data of the included studies were extracted to construct a 2 × 2 table on a per-patient basis. The overall sensitivity and specificity of the SARS-CoV-2 antigen tests were estimated using a bivariate random-effects model. RESULTS: Seventeen studies enrolling 10 912 patients were included in the present meta-analysis. For the detection accuracy of SARS-CoV-2 antigen tests, the meta-analysis generated a pooled sensitivity of 77.9% (95% confidence interval [CI]: 67.3%-85.8%) and a pooled specificity of 99.6% (95% CI: 98.9%-99.8%). The subgroup analysis of studies that examined antigen tests in symptomatic participants ≦7 days after symptom onset generated a pooled sensitivity of 79.4% (95% CI: 47.6%-94.2%) and a pooled specificity of 99.4% (95% CI: 98.2%-99.8%). Another subgroup analysis of studies that evaluated nasal swab specimens demonstrated a pooled sensitivity of 80.1% (95% CI: 65.0%-89.7%) and a pooled specificity of 98.5% (95% CI: 97.3%-9.2%). CONCLUSION: Our findings demonstrated that the antigen test performed using nasal swab specimens exhibited high sensitivity for the detection of SARS-CoV-2 within 7 days after symptom onset. Therefore, antigen testing using nasal swabs may be effective in blocking SARS-CoV-2 transmission in children.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Child , Adolescent , COVID-19/diagnosis , Sensitivity and Specificity
7.
Healthcare (Basel) ; 11(15)2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37570356

ABSTRACT

(1) Background: Patients who are critically ill or undergo major surgery are admitted to intensive care units (ICUs). Prolonged immobilization is the most likely cause of pressure injuries (PrIs) in the ICU. Previous studies of Western populations found that effective protocols could reduce the incidence of PrIs, and the efficacy of systemic targeted intervention protocols in preventing PrIs in the Chinese population needs to be surveyed. (2) Methods: We reviewed cases of PrIs in the ICUs of Taipei Veterans General Hospital from 2014 to 2019. The ICU nurses at the hospital began to implement targeted interventions in January 2017. The incidence density of PrIs was calculated by dividing the number of PrIs by person days of hospitalizations in the pre-bundle (2014-2016) and post-bundle (2017-2019) stages. Poisson regression was performed to compare the trend of incidence densities. (3) Results: The incidence density of PrIs was 9.37/1000 person days during the pre-bundle stage and 1.85/1000 person days during the post-bundle stage (p < 0.001). The relative risk (RR) was 0.197 (95% confidence interval: 0.149-0.26). The incidence densities of iatrogenic PrIs and non-iatrogenic PrIs decreased as the RRs decreased. (4) Conclusions: Targeted interventions could significantly reduce the incidence of PrIs. Healthcare providers must follow the bundle care protocol for PrI prevention to improve the quality of healthcare and promote patient health.

8.
J Chin Med Assoc ; 86(9): 842-849, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37458375

ABSTRACT

BACKGROUND: Kidney transplantation is the most important treatment for end-stage renal disease. Immunosuppressive therapies can prevent acute rejection for kidney transplant recipients. Tacrolimus is usually administered to prevent graft rejection after transplantation. Previous studies have indicated that once-daily tacrolimus may improve medication adherence. Therefore, this meta-analysis aimed to compare clinical outcomes between once-daily and twice-daily tacrolimus in de novo renal transplant patients. METHODS: Eligible studies were identified from the Cochrane Library Database, PubMed, and Embase until July 2022. Those randomized controlled trials (RCTs) evaluating once-daily versus twice-daily tacrolimus formulations in de novo renal transplantation were included. A summary risk ratio (RR) and standardized mean difference (SMD) with the 95% confidence interval (CI) were estimated using a random-effects model. RESULTS: In total, nine RCTs were included. There were no differences in biopsy-confirmed acute rejection rates between patients with once-daily and those with twice-daily tacrolimus (RR, 0.91; 95% CI, 0.73-1.13) in 12 months. Regarding renal function, there was no significant difference between the once-daily and twice-daily tacrolimus groups (SMD, -0.03; 95% CI, -0.12 to 0.07). In addition, the risk of graft failure, death, and adverse events in the first year was similar for the once-daily and twice-daily tacrolimus groups. CONCLUSION: Our major findings suggest that de novo renal transplantation recipients receiving once-daily tacrolimus immediately after transplantation have comparable efficacy and safety with those recipients who received twice-daily tacrolimus. Therefore, once-daily tacrolimus medication can be an alternative for de novo renal transplantation recipients.


Subject(s)
Kidney Transplantation , Tacrolimus , Humans , Tacrolimus/therapeutic use , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney , Transplant Recipients
9.
Article in English | MEDLINE | ID: mdl-36052556

ABSTRACT

PURPOSE: Endotracheal intubation and central venous catheterization are essential procedures in clinical practice. Simulation-based technology such as smart glasses has been used to facilitate medical students' training on these procedures. We investigated medical students' self-assessed efficacy and satisfaction regarding the practice and training of these procedures with smart glasses in Taiwan. METHODS: This observational study enrolled 145 medical students in the 5th and 6th years participating in clerkships at Taipei Veterans General Hospital between October 2020 and December 2021. Students were divided into the smart glasses or the control group and received training at a workshop. The primary outcomes included students' pre- and post-intervention scores for self-assessed efficacy and satisfaction with the training tool, instructor's teaching, and the workshop. RESULTS: The pre-intervention scores for self-assessed efficacy of 5th- and 6th-year medical students in endotracheal intubation and central venous catheterization procedures showed no significant difference. The post-intervention score of self-assessed efficacy in the smart glasses group was better than that of the control group. Moreover, 6th-year medical students in the smart glasses group showed higher satisfaction with the training tool, instructor's teaching, and workshop than those in the control group. CONCLUSION: Smart glasses served as a suitable simulation tool for endotracheal intubation and central venous catheterization procedures training in medical students. Medical students practicing with smart glasses showed improved self-assessed efficacy and higher satisfaction with training, especially for procedural steps in a space-limited field. Simulation training on procedural skills with smart glasses in 5th-year medical students may be adjusted to improve their satisfaction.


Subject(s)
Catheterization, Central Venous , Smart Glasses , Students, Medical , Clinical Competence , Control Groups , Humans , Intubation, Intratracheal , Personal Satisfaction , Taiwan
10.
Biomedicines ; 10(9)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36140271

ABSTRACT

The with-no-lysine (WNK) kinase family, comprising four serine-threonine protein kinases (WNK1-4), were first linked to hypertension due to their mutations in association with pseudohypoaldosteronism type II (PHAII). WNK kinases regulate crucial blood pressure regulators, SPAK/OSR1, to mediate the post-translational modifications (PTMs) of their downstream ion channel substrates, such as sodium chloride co-transporter (NCC), epithelial sodium chloride (ENaC), renal outer medullary potassium channel (ROMK), and Na/K/2Cl co-transporters (NKCCs). In this review, we summarize the molecular pathways dysregulating the WNKs and their downstream target renal ion transporters. We summarize each of the genetic variants of WNK kinases and the small molecule inhibitors that have been discovered to regulate blood pressure via WNK-triggered PTM cascades.

11.
J Chin Med Assoc ; 85(4): 409-413, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35383703

ABSTRACT

Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Drug Resistance, Neoplasm/genetics , Epidermal Growth Factor , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Phosphatidylinositol 3-Kinases , Protein Kinase Inhibitors/therapeutic use , Signal Transduction
12.
J Chin Med Assoc ; 85(6): 667-671, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35385421

ABSTRACT

The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.


Subject(s)
Mesenchymal Stem Cells , Stem Cells , Autophagy , Cell Differentiation , Osteogenesis
14.
Cancers (Basel) ; 14(3)2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35158774

ABSTRACT

Peptide drugs that target protein-protein interactions have attracted mounting research efforts towards clinical developments over the past decades. Increasing reports have indicated that expression of Musashi 1 (MSI1) is tightly correlated to high grade of cancers as well as enrichment of cancer stem cells. Treatment failure in malignant tumors glioblastoma multiform (GBM) had also been correlated to CSC-regulating properties of MSI1. It is thus imperative to develop new therapeutics that could effectively improve current regimens used in clinics. MSI1 and AGO2 are two emerging oncogenic molecules that both contribute to GBM tumorigenesis through mRNA regulation of targets involved in apoptosis and cell cycle. In this study, we designed peptide arrays covering the C-terminus of MSI1 and identified two peptides (Pep#11 and Pep#26) that could specifically interfere with the binding with AGO2. Our Biacore analyses ascertained binding between the identified peptides and AGO2. Recombinant reporter system Gaussian luciferase and fluorescent bioconjugate techniques were employed to determine biological functions and pharmacokinetic characteristics of these two peptides. Our data suggested that Pep#11 and Pep#26 could function as decoy peptides by mimicking the interaction function of MSI1 with its binding partner AGO2 in vitro and in vivo. Further experiments using GMB animal models corroborated the ability of Pep#11 and Pep#26 in disrupting MSI1/AGO2 interaction and consequently anti-tumorigenicity and prolonged survival rates. These striking therapeutic efficacies orchestrated by the synthetic peptides were attributed to the decoy function to C-terminal MSI1, especially in malignant brain tumors and glioblastoma.

15.
Front Cell Dev Biol ; 9: 634190, 2021.
Article in English | MEDLINE | ID: mdl-34422789

ABSTRACT

Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.

16.
Int J Mol Sci ; 22(5)2021 Feb 27.
Article in English | MEDLINE | ID: mdl-33673551

ABSTRACT

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.


Subject(s)
Endothelial Cells , Fabry Disease/therapy , Gene Editing , Induced Pluripotent Stem Cells , Mutation , alpha-Galactosidase/genetics , CRISPR-Associated Protein 9 , Fabry Disease/enzymology , Fabry Disease/genetics , Fabry Disease/pathology , Humans , Inflammation , Phenotype
17.
J Chin Med Assoc ; 84(5): 517-522, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33496511

ABSTRACT

BACKGROUND: Pedicle screw loosening (PSL) is a postsurgical complication of spinal fusion surgery that can result in morbidity. The aim of this study was to evaluate the efficacy and safety of percutaneous parapedicle screw vertebroplasty (PPSV) for pain reduction and motility improvement in patients with PSL. METHODS: The postsurgical solid inter-body fusion with inter-body bone mass formation of 32 patients who underwent lumbar-sacrum spinal fusion surgery was confirmed with plain films and CT scans. Each patient had one or two screws with symptomatic PSL and was treated with PPSV. All the patients were then followed up for 12 to 24 months. The visual analog scale (VAS) and Roland-Morris Disability Questionnaire (RMDQ) were used to evaluate each patient before the operation, after the operation, and during the follow-up period. RESULTS: A total of 32 patients with a total of 47 screws with PSL were treated with PPSV and experienced different results in terms of pain reduction (with the mean VAS score dropping from 7.97 ± 0.74 to 2.34 ± 1.59, p < 0.001) and motility improvement (with the mean RMDQ score dropping from 16.75 ± 1.84 to 7.21 ± 4.08, p < 0.001). The motility improvement was significantly correlated with pain reduction (r = 0.42, p = 0.018), with the mean follow-up period being 19.3 ± 6.2 months (range: 8-36 months). However, five patients who experienced moderate improvements had eventually received a revision operation after undergoing PPSV. CONCLUSION: The PPSV procedure is effective and safe for the reduction of pain and improvement of life quality in patients with PSL. It can thus be considered as a possible option for the revision of spinal fusion surgery.


Subject(s)
Pedicle Screws , Spinal Fusion/instrumentation , Vertebroplasty/instrumentation , Aged , Female , Humans , Lumbar Vertebrae/surgery , Male , Spinal Fusion/methods , Treatment Outcome
18.
Pancreas ; 50(10): 1415-1421, 2021.
Article in English | MEDLINE | ID: mdl-35041341

ABSTRACT

OBJECTIVE: Acute pancreatitis can usually recover after conservative treatment. Five to 10 percent of acute pancreatitis may proceed into peripancreatic fluid collection and necrosis development, called necrotizing pancreatitis (NP), which has a high mortality rate. If it is accompanied by the occurrence of abdominal compartment syndrome (ACS) and does not respond to medical therapy, surgical intervention is indicated. METHODS: We analyzed our experience of surgical intervention strategies for NP patients with medically irreversible ACS from January 1, 2004, to December 31, 2018. RESULTS: Of the 47 NP patients with ACS, mean Ranson score was 6.5, mean Acute Physiology and Chronic Health Evaluation II score was 22.2, and Modified computed tomography severity index score was all 8 or greater. The mean total postoperative hospital length of stay was 80.2 days, of which the mean intensive care unit length of stay was 16.6 days. The overall complication rate was 31.9%. The mortality rate was 8.5%. Among the 47 patients, only fungemia was significantly associated with mortality incidence. CONCLUSIONS: The combination of multiple drainage tube placement, feeding jejunostomy, and ileostomy at the same time were effective surgical intervention strategies for NP patients with ACS, which brought a lower mortality rate.


Subject(s)
Digestive System Surgical Procedures/methods , Intra-Abdominal Hypertension/surgery , Pancreatitis, Acute Necrotizing/surgery , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Intra-Abdominal Hypertension/etiology , Male , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pancreatitis, Acute Necrotizing/complications , Retrospective Studies
19.
J Chin Med Assoc ; 84(1): 68-72, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32773582

ABSTRACT

BACKGROUND: In this study, our major aim is to using multiple-steps bioinformatic analysis to predict cardiogenic genes with targeting mRNA profiling for predicting cardiogenic HoxA11 gene. METHODS: We first analyzed the microarray data with bioinformatic measurement, including combining with panel module 1 (mouse embryonic stem cells), panel module 2 (mouse induced pluripotent stem cells), and panel module 3 (gene list form literature of heart development). A literature-based comparison of the two microarrays and a software-based (Targetscan program, www.targetscan.org) comparative analysis of the two datasets. Furthermore, we select the common central pathways and potential candidate genes involved in the cardiomyocyte-lineaged differentiation and development. RESULTS: Schematic presentation of a putative miR181a target site in Hox-A11 3'UTR. The bioinformatic result showed that potential interacted cardiogenic targets of Tbx5, Tbx20, Mal2c, Nkx2.5, cTNT, Cx43, MHC, and MCK in different treatment groups of pluripotent stem cells by using a literature-based comparison of the two microarrays and a software-based gene-lineage system. CONCLUSION: Our findings support that mir181a is an up-stream regulating microRNA to target the 3'UTR of HoxA11 mRNA during the process of cardiomyocyte differentiation.


Subject(s)
Computational Biology/methods , Homeodomain Proteins/genetics , MicroRNAs/physiology , Animals , Connexin 43/metabolism , Mice , Mice, Inbred C57BL
20.
J Tissue Eng Regen Med ; 14(10): 1438-1448, 2020 10.
Article in English | MEDLINE | ID: mdl-32767844

ABSTRACT

Peripheral arterial disease (PAD) affects more than 200 million people worldwide. Recent studies suggest that oxidative stress-related inflammation can lead to the initiation and progression of PAD. Ferulic acid (FA) is a natural phenolic compound and has been proven to have antioxidant and angiogenesis effects. In this study, thermosensitive chitosan-gelatin-based hydrogel was used as a delivery vehicle of FA. The effects of hydrogel encapsulating FA (FA-gel) have been demonstrated in vitro and in vivo. The results revealed that the developed hydrogel with porous structure could provide a sustained release of FA. Post-treatment of FA-gel effectively decreased the oxidative stress-induced damage in human umbilical vein endothelial cells via decreasing endogenous reactive oxygen species production, inflammation-related gene expression and apoptosis level. In the mouse hindlimb ischemia model, the results revealed that FA-gel could improve blood flow, muscle regeneration and decreases inflammation in veins. These results suggested that FA-gel may have a therapeutic potential in PAD.


Subject(s)
Chitosan/chemistry , Coumaric Acids/therapeutic use , Hydrogels/chemistry , Injections , Peripheral Arterial Disease/drug therapy , Temperature , Animals , Apoptosis/genetics , Coumaric Acids/pharmacology , Gene Expression Regulation/drug effects , Hindlimb/drug effects , Hindlimb/pathology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice, Inbred C57BL , MicroRNAs/genetics , MicroRNAs/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/pathology , Reactive Oxygen Species/metabolism
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