Objective To investigate the protective effect of spermidine against lipopolysaccharide(LPS)-induced myocardial injury in mice and the underlying mechanism.Methods C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy.In the cell experiment,cultured rat cardiomyocytes(H9c2 cells)were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h,and the changes in cell viability and levels of lactate dehydrogenase(LDH)and cardiac troponin Ⅰ(cTNI)were assessed using CCK-8 kit,LDH detection kit and ELISA,respectively.Western blotting was performed to detect the changes in the expressions of Bax,Bcl-2,cleaved caspase-3,SLC7A11 and GPX4;the changes in reactive oxygen species(ROS)and Fe2+ levels were detected using fluorescent probes,and mitochondrial membrane potential of the cells was measured using JC-1 staining.Results Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages,which were significantly alleviated by pretreatment with spermidine.In H9c2 cells,LPS exposure significantly lowered the cell viability,increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels,decreased expressions of Bcl-2,SLC7A11 and GPX4,increased ROS production and Fe2+ level(P<0.05),and lowered mitochondrial membrane potential(all P<0.05).These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.Conclusion Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.

Objective To investigate the protective effect of spermidine against lipopolysaccharide(LPS)-induced myocardial injury in mice and the underlying mechanism.Methods C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy.In the cell experiment,cultured rat cardiomyocytes(H9c2 cells)were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h,and the changes in cell viability and levels of lactate dehydrogenase(LDH)and cardiac troponin Ⅰ(cTNI)were assessed using CCK-8 kit,LDH detection kit and ELISA,respectively.Western blotting was performed to detect the changes in the expressions of Bax,Bcl-2,cleaved caspase-3,SLC7A11 and GPX4;the changes in reactive oxygen species(ROS)and Fe2+ levels were detected using fluorescent probes,and mitochondrial membrane potential of the cells was measured using JC-1 staining.Results Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages,which were significantly alleviated by pretreatment with spermidine.In H9c2 cells,LPS exposure significantly lowered the cell viability,increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels,decreased expressions of Bcl-2,SLC7A11 and GPX4,increased ROS production and Fe2+ level(P<0.05),and lowered mitochondrial membrane potential(all P<0.05).These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.Conclusion Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.

AIM To explore the clinical effects of Shuilu Erxian Pills combined with Modified Didang Decoction on patients with early and middle stage diabetic nephropathy.METHODS Eighty-three patients were randomly assigned into control group(42 cases)for 12-week administration of Irbesartan Tablets,and observation group(41 cases)for 12-week administration of Shuilu Erxian Pills,Modified Didang Decoction and Irbesartan Tablets.The changes in clinical effects,TCM syndrome scores,blood glucose indices(FBG,HbA1c),blood lipid indices(TC,TG),renal function indices(BUN,Scr,24 h UTP,eGFR),inflammatory factors(IL-1β,hs-CRP,IL-6,TNF-α,IL-18,TGF-β1),immune function indices(lymphocyte,neutrophil,CD8+,CD3+,CD4+,CD4+/CD8+)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the observation group displayed decreased TCM syndrome scores,blood glucose indices,blood lipid indices,BUN,Scr,24 h UTP,inflammatory factors,CD8+(P＜0.05),reduced lymphocyte,neutrophil(P＜0.05),and increased eGFR,CD3+,CD4+,CD4+/CD8+(P＜0.05),which were more obvious than those in the control group(except for HbA1c,TG,SCr,24 h UTP,lymphocyte,neutrophil)(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with early and middle stage diabetic nephropathy,Shuilu Erxian Pills combined with Modified Didang Decoction can safely and effectively improve clinical symptoms,whose mechanism may contribute to the reduction of inflammatory levels and improvement of immune functions.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Background: and Purpose This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). Conclusion An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Background and Objectives: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. Methods: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. Results: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14–1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. Conclusions Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.