Eradication therapy may decrease the risk of immune thrombocytopenia after Helicobacter pylori infection: a retrospective cohort study in Taiwan.

BACKGROUND: Helicobacter pylori (HP) eradication therapy (HPE) is recommended for patients with unexplained immune thrombocytopenia (ITP); however, the role of HPE in preventing ITP in patients with HP infection remains unclear. Therefore, this study was designed to clarify it. METHODS: This study was conducted at a tertiary medical center and included all adult patients with HP infection between January 1, 2016 and December 31, 2018. We compared the risk of developing ITP between patients with and without HPE. All patients were followed up until December 31, 2020. RESULTS: After excluding patients with thrombocytopenia, 1995 adult patients with HP infection, including 1188 patients with HPE and 807 patients without HPE, were included in this study. The mean age of the patients with HPE was 57.9 years, whereas that of those without HPE was 61.6 years. The percentage of males was 56% in patients with HPE and 59% in those without HPE. Patients without HPE had a higher risk of ITP than those with HPE after adjusting for age, sex, the Charlson Comorbidity Index, and comorbidities [adjusted odds ratio (OR) 1.76; 95% confidence interval (CI) 1.16-2.68]. Stratified analyses showed that the higher risk was found only in males (adjusted OR: 1.70; 95% CI 1.03-2.80). In addition to HPE, male sex and anemia were independent predictors of ITP in patients with HP infection. CONCLUSION: This study showed that adult patients with HP infection not receiving HPE had a higher risk of developing ITP. We suggest that HPE should be considered, particularly in males and those who have anemia, to prevent ITP.

Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.

Update on Regulation of Regenerative Medicine in Taiwan.

Due to rapid development of biotechnology in recent years, the field of regenerative medicine has attracted considerable attention. Regenerative medicine-related regulations have been established in several countries to ensure the quality, safety, and efficacy of innovative treatments. Considering the diversity of regenerative medicine, the regulatory framework in Taiwan has been adjusted in response to global trend and local demand. Before 2010, cell and gene therapies were regarded as "new medical practice" under the "Medical Care Act." Along with the establishment of Taiwan Food and Drug Administration (TFDA) in 2010, regenerative medicine was regulated as "medicinal products" under the "Pharmaceutical Affairs Act." Then, the Ministry of Health and Welfare (MOHW) established a new dual-track regulatory pathway for regenerative medicine in 2016. The dual-track pathway divided regenerative medicine into medical practices and medicinal products, aiming to improve the accessibility of new treatments to patients and maintain the flexibility for clinical operations. In order to refine the regulation, the MOHW proposed two draft Acts for regenerative medicine in 2022. The two draft Acts are currently under legislative process. It is expected that the research and development of regenerative medicine can be further accelerated, thus providing early access to innovative therapies for patients in the future.

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BACKGROUND: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment. METHODS: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored. RESULTS: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders. CONCLUSION: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.

Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.

Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease.

Glutamate is the predominant excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter 2 (EAAT2) is primarily responsible for clearance of extracellular glutamate to prevent neuronal excitotoxicity and hyperexcitability. EAAT2 plays a critical role in regulation of synaptic activity and plasticity. In addition, EAAT2 has been implicated in the pathogenesis of many central nervous system disorders. In this review, we summarize current understanding of EAAT2, including structure, pharmacology, physiology, and functions, as well as disease relevancy, such as in stroke, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, major depressive disorder, and addiction. A large number of studies have demonstrated that up-regulation of EAAT2 protein provides significant beneficial effects in many disease models suggesting EAAT2 activation is a promising therapeutic approach. Several EAAT2 activators have been identified. Further understanding of EAAT2 regulatory mechanisms could improve development of drug-like compounds that spatiotemporally regulate EAAT2.

Regulation of Cell and Gene Therapy Medicinal Products in Taiwan.

Owing to the rapid and mature development of emerging biotechnology in the fields of cell culture, cell preservation, and recombinant DNA technology, more and more cell or gene medicinal therapy products have been approved for marketing, to treat serious diseases which have been challenging to treat with current medical practice or medicine. This chapter will briefly introduce the Taiwan Food and Drug Administration (TFDA) and elaborate regulation of cell and gene therapy medicinal products in Taiwan, including regulatory history evolution, current regulatory framework, application and review procedures, and relevant jurisdictional issues. Under the promise of quality, safety, and efficacy of medicinal products, it is expected the regulation and environment will be more flexible, streamlining the process of the marketing approval of new emerging cell or gene therapy medicinal products and providing diverse treatment options for physicians and patients.

Mitochondrial Mechanisms in Temozolomide Resistance: Unraveling the Complex Interplay and Therapeutic Strategies in Glioblastoma.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor, with temozolomide (TMZ) being the standard chemotherapeutic agent for its treatment. However, TMZ resistance often develops, limiting its therapeutic efficacy and contributing to poor patient outcomes. Recent evidence highlights the crucial role of mitochondria in the development of TMZ resistance through various mechanisms, including alterations in reactive oxygen species (ROS) production, metabolic reprogramming, apoptosis regulation, biogenesis, dynamics, stress response, and mtDNA mutations. This review article aims to provide a comprehensive overview of the mitochondrial mechanisms involved in TMZ resistance and discuss potential therapeutic strategies targeting these mechanisms to overcome resistance in GBM. We explore the current state of clinical trials targeting mitochondria or related pathways in primary GBM or recurrent GBM, as well as the challenges and future perspectives in this field. Understanding the complex interplay between mitochondria and TMZ resistance will facilitate the development of more effective therapeutic strategies and ultimately improve the prognosis for GBM patients.

Impact of a pyridazine derivative on tripartite synapse ultrastructure in hippocampus: a three-dimensional analysis.

Introduction: We previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer's disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially. While biochemical evidence supports the hypothesis that the compound enhances the structural plasticity of the tripartite synapse, its direct structural impact has not been investigated. Methods: Volume electron microscopy was used to study the hippocampal tripartite synapse three-dimensional structure in 3-month-old wild-type FVB/NJ mice after LDN/OSU-0215111-M3 treatment. Results: LDN/OSU-0215111-M3 increased the size of tertiary apical dendrites, the volume of mushroom spines, the proportion of mushroom spines containing spine apparatus, and alterations in the spine distribution across the surface area of tertiary dendrites. Compound also increased the number of the PAP interacting with the mushroom spines as well as the size of the PAP in contact with the spines. Furthermore, proteomic analysis of the isolated synaptic terminals indicated an increase in dendritic and synaptic proteins as well as suggested a possible involvement of the phospholipase D signaling pathway. To further validate that LDN/OSU-0215111-M3 altered synaptic function, electrophysiological studies showed increased long-term potentiation following compound treatment. Discussion: This study provides direct evidence that pyridazine derivatives enhance the structural and functional plasticity of the tripartite synapse.

Plumbagin induces the apoptosis of drug-resistant oral cancer in vitro and in vivo through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction.

BACKGROUND: Oral cancer is one of the leading causes of cancer-related deaths worldwide. Chemotherapy is widely used in the treatment of oral cancer, but its clinical efficacy is limited by drug resistance. Hence, novel compounds capable of overcoming drug-resistance are urgently needed. PURPOSE: Plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, has been used to treat various cancers. In this study, we investigated the anticancer effects of PG on drug-resistant oral cancer (CR-SAS) cells, as well as the underlying mechanism. METHODS: MTT assays were used to evaluate the effect of PG on the viability of CR-SAS cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined using flow cytometry. Protein expression levels were detected by western blotting. RESULTS: The results show that PG reduces the viability and causes the apoptosis of CR-SAS cells. PG is able to induce intracellular and mitochondrial ROS generation that leads to mitochondrial dysfunction. Furthermore, endoplasmic reticulum (ER) stress was triggered in PG-treated CR-SAS cells. The inhibition of ROS using N-acetylcysteine (NAC) abrogated the PG-induced ER stress and apoptosis, as well as the reduction in cell viability. Meanwhile, similar results were observed both in zebrafish and in murine models of drug-resistant oral cancer. CONCLUSION: Our results indicate that PG induces the apoptosis of CR-SAS cells via the ROS-mediated ER stress pathway and mitochondrial dysfunction. It will be interesting to develop the natural compound PG for the treatment of drug-resistant oral cancer.

Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus.

Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased glial glutamate transporter EAAT2, the major glutamate transporter, could prevent seizure activity and reduce epileptogenic processes. EAAT2 transgenic mice, which have a 1.5-2 fold increase in EAAT2 protein levels as compared to their non-transgenic counterparts, were tested in a pilocarpine-induced status epilepticus (SE) model. Several striking phenomena were observed in EAAT2 transgenic mice compared with their non-transgenic littermates. First, the post-SE mortality rate and chronic seizure frequency were significantly decreased. Second, neuronal degeneration in hippocampal subfields after SE were significantly reduced. Third, the SE-induced neurogenesis and mossy fiber sprouting were significantly decreased. The severity of cell loss in epileptic mice was positively correlated with that of mossy fiber sprouting and chronic seizure frequency. Our results suggest that increased EAAT2 expression can protect mice against SE-induced death, neuropathological changes, and chronic seizure development. This study suggests that enhancing EAAT2 protein expression is a potential therapeutic approach.

Protective effect of caffeic acid on paclitaxel induced anti-proliferation and apoptosis of lung cancer cells involves NF-κB pathway.

Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC(50) dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls.

Safe-Sex Behavioral Intention of Chinese College Students: Examining the Effect of Sexual Knowledge Using the Theory of Planned Behavior.

Numerous contemporary studies have examined safe sexual behavior among college students. In China, families are reluctant to discuss sexual behavior, thus understanding and exploring the sexual knowledge of college students and the promotion of safe sexual behavior is essential. On the basis of the theory of planned behavior (TPB), a cognitive behavioral theory that is widely used to predict human social behavior, we conducted an in-depth investigation of the factors influencing the sexual behavioral intentions of Chinese college students. We referenced the relevant literature to develop a TPB-based model for analyzing differences in sexual knowledge. Our statistical analysis revealed the following: (1) subjective norms and behavior control are key variables that influence the safe sexual behavior of college students; (2) attitudes and safe-sex behavioral intentions are influential in groups with extensive sexual knowledge; (3) behavioral control and subjective norms influence the differences in the comparative sexual knowledge of students. On the basis of the present results, we propose research recommendations and directions for the development of sex education in China.

Research Landscape of Artificial Intelligence and e-Learning: A Bibliometric Research.

While an increasing number of organizations have introduced artificial intelligence as an important facilitating tool for learning online, the application of artificial intelligence in e-learning has become a hot topic for research in recent years. Over the past few decades, the importance of online learning has also been a concern in many fields, such as technological education, STEAM, AR/VR apps, online learning, amongst others. To effectively explore research trends in this area, the current state of online learning should be understood. Systematic bibliometric analysis can address this problem by providing information on publishing trends and their relevance in various topics. In this study, the literary application of artificial intelligence combined with online learning from 2010 to 2021 was analyzed. In total, 64 articles were collected to analyze the most productive countries, universities, authors, journals and publications in the field of artificial intelligence combined with online learning using VOSviewer through WOS data collection. In addition, the mapping of co-citation and co-occurrence was explored by analyzing a knowledge map. The main objective of this study is to provide an overview of the trends and pathways in artificial intelligence and online learning to help researchers understand global trends and future research directions.

Bibliometric-Based Evaluation of the Neuromarketing Research Trend: 2010-2021.

Neuromarketing has become a new and important topic in the field of marketing in recent years. Consumer behavior research has received increasing attention. In the past decade, the importance of marketing has also been recognized in many fields such as consumer behavior, advertising, information systems, and e-commerce. Neuromarketing uses neurological methods to determine the driving forces behind consumers' choices. Various neuroscience tools, such as eye movements, have been adopted to help reveal how consumers react to particular advertisements or objects. This information can be used as the basis for new advertising campaigns and brand promotions. To effectively explore the research trends in this field, we must understand the current situation of neuromarketing. A systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. In this study, journals that focused on neuromarketing in the field of marketing between 2010 and 2021 were analyzed. These journals were core journals rated by the Association of Business Schools with three or more stars. According to the data analysis results, neuromarketing has 15 main journals with relevant papers. Based on the data collected by the Web of Science (WOS), this study mainly collected 119 references and analyzed the most productive countries, universities, authors, journals, and prolific publications in the field of neuromarketing via Citespace. Through the analysis of knowledge maps, this study explored the mapping of co-citation, bibliographic coupling (BC), and co-occurrence (CC). Moreover, the strongest citation bursts were used to study popular research at different time stages and analyze the research trends of neuromarketing research methods and tools. This study provides an overview of the trends and paths in neuromarketing, which can help researchers understand global trends and future research directions.

Roles and Research Trends of Neuroscience on Major Information Systems Journal: A Bibliometric and Content Analysis.

Over the past decade, neuroscience has been integrated into information systems as a new methodology and perspective to study and solve related problems. Therefore, NeuroIS has emerged as a new cutting-edge research field. This review aimed to identify, summarize, and classify existing NeuroIS publications through knowledge mapping and bibliometric analysis. To effectively understand the development trend of NeuroIS, this study referred to the journal selection index of the Association of Business Schools in 2021 and journals above three stars in the field of information management as the main selection basis. A total of 99 neuroscience papers and their citation data were included from 19 major information systems journals of SCI/SSCI. This study analyzed bibliometric data from 2010 to 2021 to identify the most productive countries, universities, authors, journals, and prolific publications in NeuroIS. To this end, VOSviewer was used to visualize mapping based on co-citation, bibliographic coupling, and co-occurrence. Keywords with strong citation bursts were also identified in this study. This signifies the evolution of this research field and may reveal potential research directions in the near future. In selecting research methods and analysis tools for NeuroIS, content analysis was used to further conclude and summarize the relevant trends. Moreover, a co-citation network analysis was conducted to help understand how the papers, journals, and authors in the field were connected and related, and to identify the seminal or pioneering major literature. For researchers, network maps visualized mainstream research and provided a structural understanding of NeuroIS. The review concludes by discussing potential research topics in this field.

The Impact of Career Competence on Career Sustainability Among Chinese Expatriate Managers Amid Digital Transformation in Vietnam: The Role of Lifelong Learning.

Digitalization and advanced technologies are replacing human jobs. Around the world, many people have lost their jobs due to increasing digitalization. Similarly, Chinese expatriates associated with the manufacturing sector in emerging countries such as Vietnam face similar challenges. Therefore, Chinese expatriates need to bring competitiveness in their competencies. This competitiveness brings sustainability to their career. The aim of this study is to investigate the impact of career competencies on career sustainability. Moreover, we test the mediating effect of lifelong learning in the relationship between career competencies and career sustainability. A questionnaire survey approach was used in this study. The target population was the Chinese expatriate managers working at China-invested manufacturing multinational organizations in Vietnam. To estimate the proposed relationships, we use structural equation modeling. The results are confirmed that in the direct relationship career competence has a positive impact on career sustainability. The findings of this study also indicate that career competencies have a positive impact on lifelong learning. Furthermore, outcomes confirmed that lifelong learning has a positive impact on career sustainability. Similarly, results are also confirmed that lifelong learning is positively mediating between career competencies and career sustainability. Therefore, the empirical results of this article identify that lifelong learning has a critical impact on sustainable careers. Specifically, this study is useful for mid-level managers who are associated with multinational organizations. At the end of this article, we also explained the practical implications, limitations, and future research directions.

Effect of diabetes mellitus comorbidity on outcomes in stages II and III colorectal cancer.

AIM: The effects of diabetes mellitus (DM) on the outcomes of colorectal cancer (CRC) are controversial. This retrospective study evaluated the effects of DM on American Joint Committee on Cancer (AJCC, 7th) Stages II and III CRC patients who received curative surgery. METHODS: We reviewed the records of CRC patients who were treated from January 2008 to December 2014 and identified the presence of DM and hypertension prior to CRC diagnosis. Cox proportional hazards analyses were used for prognostic factor determination, and survival was analyzed using the Kaplan-Meier method with the log-rank test. RESULTS: Total of 1066 consecutive eligible patients with stage II/III CRC were enrolled. There were 326 (30.6%) patients diagnosed with DM, and 311 (29.2%) CRC patients had recurrence. Patients with DM did not have a higher recurrence risk (p = 0.183) but had higher mortality (adjusted hazard ratio [aHR] = 1.381; 95% conference interval [CI], 1.069-1.782). In addition, HbA1c (≥7 vs. <7) was not associated with recurrence (p = 0.365). Patients with DM had more hypertension than patients without DM (69.1% vs. 37.6%, p < 0.001). A lower recurrence risk was noted in patients with hypertension (p = 0.002), but the overall survival (OS) did not reach statistical significance (aHR = 0.910; 95% CI, 0.707-1.169). CONCLUSION: In our study, DM was a poor prognostic factor for survival in curative CRC patients. More studies are required to elucidate the effects that DM and other metabolic disorders, such as hypertension, have on the prognosis of patients with CRC.

Risk of dementia in colorectal cancer patients receiving chemotherapy: A nationwide cohort study.

BACKGROUND: Studies have reported conflicting evidence regarding whether chemotherapy leads to dementia. This study aimed to determine whether chemotherapy increases dementia risk in Taiwanese patients with colorectal cancer (CRC). METHODS: Data from the Taiwan Cancer Registry and National Health Insurance Research Database were used. Patients newly diagnosed as having CRC between 2007 and 2015 without prior history of dementia or neurodegenerative disorders were identified. Based on whether they underwent chemotherapy, patients were divided into chemotherapy and non-chemotherapy groups. Those who later developed dementia were identified using validated diagnostic codes. The Fine and Gray subdistribution hazard model for all-cause dementia with competing risk of death was applied for all patients or each stratified group. RESULTS: A total of 76,130 patients with CRC were included, with 45,872 (60.25%) in the chemotherapy group and 30,258 (39.75%) in the non-chemotherapy group. A higher incidence of dementia was observed in the non-chemotherapy group compared with the chemotherapy group (3.75% vs. 2.40%, p < 0.0001), but the risk of dementia did not differ between the groups (adjusted subdistribution hazard ratio [HRSD] = 0.97, 95% confidence interval [CI]: 0.88-1.06, p = 0.492). In the stratified analysis, chemotherapy was a risk factor for dementia in patients aged > 80 years (adjusted HRSD = 1.20, 95% CI: 1.03-1.40, p = 0.0190), whereas gender, clinical cancer stage, comorbidities, surgery, and radiation therapy had no impact on the risk of dementia. CONCLUSION: Chemotherapy increased the risk of dementia in elderly patients with CRC, highlighting the necessity to monitor their cognitive function after chemotherapy.