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Kai-Chun Cheng,1,* Yingxiao Li,1,2,* Wei-Ting Chang,2,3 Feng Yu Kuo,4 Zhih-Cherng Chen,3,5 Juei-Tang Cheng2,6 1Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan; 2Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan; 3Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan; 4Cardiovascular Center, Kaohsiung Veterans General Hospital, Kaohsiung City 81362, Taiwan; 5Department of Pharmacy, Chia Nan University of Pharmacy and Science, Jean-Tae, Tainan City 71701, Taiwan; 6Institute of Medical Sciences, Chang Jung Christian University, Gueiren, Tainan City 71101, Taiwan *These authors contributed equally to this work Background: Metabolic syndrome (MS) is known to be associated with hypertension, insulin resistance, and dyslipidemia, and it raises the risk for cardiovascular diseases and diabetes mellitus. Telmisartan is used in clinic as an angiotensin II receptor blocker and it is also identified as activating peroxisome proliferator-activated receptors δ (PPARδ). Activation of PPARδ produced beneficial effects on fatty acid metabolism and glucose metabolism. This study aims to investigate the effects of telmisartan on the modulation of MS in rats fed a high-fat/high-sodium diet. Methods: Rats were fed with a high-fat/high-sodium diet and received injections of streptozotocin at low dose to induce MS. Then, rats with MS were treated with telmisartan. The weight, glucose tolerance, and insulin sensitivity were measured. The lipid profiles were also obtained. The weights of retroperitoneal and epididymal fat pads were determined. The role of PPARδ in telmisartan treatment was identified in rats pretreated with the specific antagonist GSK0660. Results: The results showed that telmisartan, but not losartan, significantly reduced plasma glucose and plasma insulin, and improved insulin resistance in rats with MS. Telmisartan also decreased blood pressure and lipids more significantly than losartan. Moreover, GSK0660 effectively reversed the effects of telmisartan in the MS rats. In the MS group, telmisartan activated PPARδ to enhance the levels of phosphorylated GLUT4 in muscle or the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver, which was also abolished by GSK0660. Telmisartan is useful to ameliorate hypertension and insulin resistance in rats with MS. Telmisartan improves the insulin resistance through increased expression of GLUT4 and down-regulation of PEPCK via PPARδ-dependent mechanisms. Conclusion: Telmisartan has been proven to ameliorate MS, particularly in the prediabetes state. Therefore, telmisartan is suitable to develop for the management of MS in clinics. Keywords: metabolic syndrome, telmisartan, PPARδ, GSK0660, diet

Purpose: To examine the effects of ascorbic acid (AA) administrated during cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of ventricular fibrillation (VF) and electrical shock (ES).Methods: VF was induced in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and then one ES of 5 J. At the start of CPR, animals received either intravenous administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9% saline (VF + ES group). After ES, animals were immediately killed. Myocardial lipoxidation was determined by malondialdehyde (MDA) assay. The histology and ultrastructural changes of myocardium were also evaluated. The mitochondrial permeability transition pore (mPTP) opening was measured based on the mitochondrial swelling rate. The complex activities and respiration of mitochondria were assessed, too.Results: Increased myocardial injury and mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated such damages. Both AA and Tempol improved accelerated mitochondrial swelling; decreased complex activities and respiratory dysfunction occurred in the VF + ES group. The animals receiving AA and Tempol during CPR had better successful resuscitation rates and 72-h survival than the VF + ES group.Conclusions: Intravenous administration of AA and Tempol at the start of CPR may reduce lipid peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate resuscitation, and improve outcomes after VF + ES. [ABSTRACT FROM AUTHOR]

Prognózu je treba prísne personalizovat a rozhodnutí casove neohranicovat sedmym dnem po zresuscitované srdecní zástave, a to ani pri a po pokracující kvalifikované pozástavové intenzivní péci. Pozvolné zlepsování bylo zaznamenáno zejména mezi muzi, po obnovení spontánního obehu jiz behem neodkladné resuscitace v prednemocnicní fázi, po udrzování normotermie, po eCPR a bez vyznamne patologického nálezu v HDEEG. Akademická vyzkumná skupina z Tchajwanu se v retrospektivní studii z let 2011-2019, podporené 28 citacemi, venovala podrobnému rozboru, zda po netraumatické akutní srdecní zástave u dospelych je mozno povazovat následny casovy interval 7 dnu v pokracující pozástavové intenzivní péci za prognosticky spolehlivy pro urcení neurologické kvality dalsího zivota. [Extracted from the article]

BACKGROUND Inherited deficiencies in antithrombin (AT), protein C (PC), and protein S (PS) increase the risk of venous thromboembolism (VTE). The efficacy and safety of direct oral anticoagulants (DOACs) in severe VTE cases after mechanical thrombectomy are uncertain. This study aimed to evaluate the use of DOACs combined with mechanical thrombectomy in 55 patients with VTE, including 11 patients with confirmed deep vein thrombosis (DVT) and pulmonary thromboembolism (PE), 27 patients with DVT alone, and 17 with pulmonary thromboembolism alone, from a single center between January 2016 and December 2023. MATERIAL AND METHODS All patients with symptomatic VTE confirmed by computed tomography underwent mechanical thrombectomy. Fourteen patients with reduced AT (n=4), PC (n=6), and PS (n=4) function were classified as group 1, while the remaining 41 without thrombophilia were classified as group 2. The outcomes, including recurrent VTE, bleeding events, and all-cause mortality, were compared between patients with and without thrombophilia. RESULTS DOAC use was similar between the groups. One patient in the thrombophilia group switched DOACs due to bleeding, while 7 in the non-thrombophilia group changed due to bleeding or recurrent VTE. Recurrent VTE was higher in the non-thrombophilia group (7.1% vs 17.1%; P=0.664), while bleeding events were more frequent in the thrombophilia group (35.7% vs 17.1%; P=0.259); however, neither difference was statistically significant. All-cause mortality was similar between groups (7.1% vs 6.7%; P=0.903). CONCLUSIONS The study found no difference in the efficacy and safety of DOACs between VTE patients with and without inherited thrombophilia undergoing mechanical thrombectomy.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Resuscitation Council, American Heart Association Inc., International Liaison Committee on Resuscitation. Published by Elsevier B.V. All rights reserved.)

For the primary prevention of atherosclerotic cardiovascular disease (ASCVD), the recommended treatment target for each modifiable risk factor is as follows: reducing body weight by 5-10%; blood pressure < 130/80 mmHg (systolic pressure < 120 mmHg in high-risk individuals); low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL in high-risk individuals, LDL-C < 115 mg/dL in moderate-risk individuals, LDL-C < 130 mg/dL in low-risk individuals, and LDL-C < 160 mg/dL in those with a minimal; complete and persistent abstinence from cigarette smoking; hemoglobin A1C < 7.0%; fulfilling recommended amounts of the six food groups according to the Taiwan food guide; and moderate-intensity physical activity 150 min/wk or vigorous physical activity 75 min/wk. For the primary prevention of ASCVD by pharmacological treatment in individuals with modifiable risk factors/clinical conditions, statins are the first-line therapy for reducing LDL-C levels; some specific anti-diabetic drugs proven to be effective in randomized controlled trials for the primary prevention of ASCVD are recommended in patients with type 2 diabetes mellitus; pharmacological treatment is recommended to assist in weight management for obese patients with a body mass index ≥ 30 kg/m 2 (or 27 kg/m 2 who also have at least one ASCVD risk factor or obesity-related comorbidity); an angiotensin-converting enzyme inhibitor, a glucagon-like peptide-1 receptor agonist, a sodium-dependent glucose cotransporter-2 inhibitor, and finerenone can be used in diabetic patients with chronic kidney disease for the primary prevention of ASCVD. Of note, healthcare providers are at full discretion in clinical practice, owing to the diversity of individuals and practice, and the availability of resources and facilities., Competing Interests: Ting-Hsing Chao has been on the speaker bureau for Astrazeneca, Bayer, Eli Lilly, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi, Tanabe, and TSH biopharm. All other authors report no potential conflicts of interest in relation to these guidelines.

Background: While single-incision laparoscopic cholecystectomy (SILC) has gained more popularity in recent years, its application to elderly patients needs further evaluation. Few SILC studies regarded this rapidly growing vulnerable population, and single-incision laparoscopic common bile duct exploration (SILCBDE) was never mentioned. We conducted an observational study of 146 routine SILCBDE to address this issue., Methods: One hundred forty-six consecutive patients underwent SILCBDE with concomitant cholecystectomies during a period of 6 years (July 2012-June 2016 and July 2018-July 2020). Forty patients with an age of 65 years or older were the study target. Characteristics and operative outcomes were compared with the remaining 106 younger patients by retrospective chart review. The primary outcomes include complications and mortality, while the secondary outcomes contain intraoperative blood loss, operative time, procedural conversions, postoperative length of hospital stay, and bile duct stone recurrence., Results: There was no mortality. The bile duct stone clearance rate was 98.6%. The elderly group had higher American Society of Anesthesiologists (ASA) scores, higher comorbidity rate, higher acute cholangitis rate, lower completion intraoperative cholangiography (IOC) rate, longer operative time, more blood loss, longer postoperative hospital stay (p < .001), longer total hospital stay (p < .001), higher procedural conversion rate (p < .05), higher complication rate (p < .001), and the exclusive open conversion (2.5%). The difference in complications derived from Clavien-Dindo grade I., Conclusion: Routine SILCBDE with concomitant cholecystectomy by experienced surgeons is safe and efficacious for elderly patients as for younger patients. Randomized controlled trials are anticipated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

Background: Patients with severe stroke are at high risk of secondary neurologic decline (ND) from the development of malignant cerebral edema (MCE). However, early infarcts are hard to diagnose on conventional head computed tomography (CT). We hypothesize that high-energy (190 keV) virtual monochromatic imaging (VMI) from dual-energy CT (DECT) imaging enables earlier detection of ND from MCE., Methods: Consecutive patients with severe stroke with National Institute of Health Stroke Scale (NIHSS) scores > 15 and DECT within 10 h of mechanical thrombectomy from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma type 2 transformation. Retrospective analysis of clinical and novel variables included the VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. The primary outcome was secondary ND, defined using a composite outcome variable of clinical worsening (increase in NIHSS score ≥ 4 or decrease in Glasgow Coma Scale score > 2) or malignant radiographical edema (midline shift ≥ 5 mm at the level of the septum pellucidum). Fisher's exact test and Wilcoxon's test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes., Results: Eighty-four patients with severe stroke with a median age of 67.5 (interquartile range [IQR] 57-78) years and an NIHSS score of 22 (IQR 18-25) were included. Twenty-nine patients had ND. The VMI ASPECTS, total iodine content, and VMI infarct volume were associated with ND. The VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of ND after adjusting for age, sex, initial NIHSS score, and tissue plasminogen activator administration, with areas under the receiver operating characteristic curve (AUROC) of 0.691 (95% confidence interval [CI] 0.572-0.810), 0.877 (95% CI 0.800-0.954), and 0.845 (95% CI 0.750-0.940). By including all three predictors, the model achieved an AUROC of 0.903 (95% CI 0.84-0.97) and was cross-validated by the leave one out method, with an AUROC of 0.827., Conclusions: The VMI ASPECTS and VMI infarct volume from DECT are superior to the conventional CT ASPECTS and are novel predictors for secondary ND due to MCE after severe stroke. Clinical trial registration ClinicalTrials.gov identifier: NCT04189471., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: Cancer patients face a four- to sevenfold higher risk of venous thromboembolism (VTE) than the general population. Novel oral anticoagulants (NOACs) provide convenient alternatives to traditional therapies., Methods: We performed a systematic literature search across PubMed, Embase, and the Cochrane Library, targeting studies that examined the use of NOACs in cancer-associated VTE. The search included randomized controlled trials (RCTs). Selected studies compared NOACs with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKA) in cancer patients diagnosed with VTE. A meta-analysis using a random-effects model was applied to estimate pooled effect sizes for outcomes., Results: In this meta-analysis, we included 12 RCTs. Results showed NOACs were more effective than LMWH in preventing VTE recurrence (RR 0.66, 95% CI 0.52-0.83, p = 0.0004). Compared with VKAs, NOACs showed no significant difference (RR 0.63, 95% CI 0.34-1.15, p = 0.13). However, this finding is limited by the small patient sample. Major bleeding outcomes were similar between NOACs and LMWH/VKAs (RR 1.24, 95% CI 0.85-1.80, p = 0.28; RR 0.77, 95% CI 0.39-1.53, p = 0.46, respectively). Meta-regression analysis indicated a statistically significant positive correlation between mortality and major bleeding events when comparing NOACs with LMWH (p = 0.049). There was no significant difference in all-cause mortality between patients treated with NOACs and those treated with LMWH (RR 1.04, 95% CI 0.92-1.18, p = 0.54) or VKAs (RR 0.94, 95% CI 0.72-1.23, p = 0.65)., Conclusion: Meta-analysis shows NOACs, especially factor Xa inhibitors, reduce VTE recurrence in cancer patients more effectively than LMWH. Comparison between NOACs and VKAs is inconclusive due to limited patient data. Further research is needed to assess NOACs' efficacy and safety against VKAs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since females grow faster in penaeid shrimp, all-female aquaculture was proposed. Environmental conditions in the Pacific white shrimp did not found to affect genetic sex determination (ZZ/ZW system). The androgenic gland (AG)-secreting insulin-like androgenic gland hormone (IAG) is a key controlling factor in crustacean male differentiation. However, functional sex reversal (neo-male) in penaeid shrimp has not yet been achieved by manipulating the IAG-sexual switch. Therefore, understanding the molecular mechanisms of gonadal differentiation may help build appropriate tools to generate neo-male (ZW) for all-female breeding. This study describes the potential role of the novel penaeid-specific testicular zinc finger protein (pTZFP) in the gonads of Pacific white shrimp. First, pTZFP transcripts show a male-bias expression pattern in undifferentiated gonads, which is then exclusively expressed in the testis and absent or slightly expressed in the ovary and other tissues. Besides, the knockdown of pTZFP in undifferentiated males results in smaller testes but no sex reversal. Immunohistochemical (IHC) staining of proliferating cell nuclear antigen (PCNA) further confirmed that the smaller testes in pTZFP-deficient males are due to the lower proliferating activity of spermatogonia. These data reveal that pTZFP may be involved in testicular development but have fewer effects on gonadal differentiation. Moreover, testicular pTZFP transcription levels were not reduced with estradiol-17β (E2) administration or AG excision. Therefore, our data suggest that pTZFP may regulate testicular development through downstream genes regulating spermatogonia proliferation. Moreover, our data provide an appropriate molecular marker for identifying the sex of undifferentiated gonads., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Stress associated with manipulation during electrocardiography (ECG) recording in cats potentially limits the assessment of autonomic function through heart rate variability (HRV) in the feline population. This study proposed an alternative, cat friendly, stethoscopic approach to evaluate HRV with an easily acquired vasovagal tonus index (VVTI)., Methods: The aim of this prospective study was to evaluate whether VVTI derived from heart sound signals could distinguish between relaxed and stimulated states. A total of 29 cats with 56 recordings of heart sound and ECG on 31 occasions were included. In 25 cats in their home environment, a stethoscope connected to a digital recording device was used to record 2 mins of heart sounds twice - with the cats in a relaxed state and immediately after stimulation. The VVTI was calculated from 20, 60 and 120 consecutive beat-to-beat intervals on the heart sound spectrogram (stethoscopic-VVTI 20, 60 and 120), using the natural logarithm of the variance of the intervals based on previous literature. A 2-min ECG recording was obtained at home with the intention of avoiding strict restraint. To demonstrate the feasibility of the stethoscopic approach in a hospital setting, six cats (two of which were also recorded at home) underwent heart sound and ECG recordings during planned veterinary visits., Results: Stethoscopic-VVTI 20 (5.43 to 4.79, P  = 0.001), 60 (6.20 to 5.18, P <0.001) and 120 (6.24 to 5.60, P  = 0.02) all significantly decreased after stimulation, indicating a reduced vasovagal tone as expected. Calculations of stethoscopic-VVTI from different sections of the recording yielded statistically similar results. Stethoscopic-VVTI showed a negative correlation with the corresponding heart rate. Bland-Altman analysis revealed a mean bias for the differences between stethoscopic-VVTI and ECG-VVTI of 0.50 and 1.07 at home and in the hospital, respectively., Conclusions and Relevance: VVTI can be successfully detected through a stethoscopic approach, serving as a less stressful tool for HRV evaluation in cats during routine auscultation., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Established protocols for implementing high-quality targeted temperature management (TTM) provide guidance concerning the cooling rate, duration of maintenance, and rewarming speed. However, whether compliant to TTM protocols results in improved survival and better neurological recovery has not been examined., Methods: A retrospective cohort study enrolled 1141 survivors of non-traumatic adult cardiac arrest with a pre-arrest cerebral performance category (CPC) score of 1-2 from 2015 to 2020 at a tertiary medical center. Of the survivors, 330 patients who underwent TTM were further included. Patients with spontaneous hypothermia (<35 °C) (n = 107) and expired during the TTM (n = 21) were excluded. A total of 202 patients were thus enrolled. One hundred and ten patients underwent TTM that completely complied with the protocol (protocol-complaint group), but 92 patients deviated in some manner from the protocol (protocol non-compliant group)., Results: Fifty patients (50%) and 46 patients (50%) in the protocol-compliant and non-compliant groups, respectively, did not survive to hospital discharge. In the protocol-compliant group, 42 patients (38.2%) had favorable neurological recovery, compared with 32 patients (34.8%) in the protocol non-compliant group. After adjusting for age, initial shockable rhythm, witnessed collapse, and cardiopulmonary resuscitation duration, protocol non-compliant was associated with the poor neurological outcomes (aOR 2.44, 95% CI = 1.13-5.25), but not with in-hospital mortality (aOR 1.31, 95% CI = 0.70-2.47). The most common reason for noncompliance was a prolonged duration reaching the target temperature (n = 33, 58.7%). The number of phases of non-compliant was not significantly associated with in-hospital mortality or poor neurological recovery., Conclusion: Among cardiac arrest survivors undergoing TTM, those who did not receive TTM that in compliance with the protocol were more likely to experience poor neurological recovery than those whose TTM fully complied with the protocols. The most frequently identified deviation was a prolonged duration to reaching the target temperature., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin-aldosterone system inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction, its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/d), spironolactone (80 mg/kg/d), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared with that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced heart failure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Ethnopharmacological Relevance: Periostracum Cicadae (PC), the molted exoskeleton of the cicada Cryptotympana pustulata Fabricius, is frequently employed in Chinese herbal medicine. Based on traditional therapies and pharmacological studies, PC appears to have immunomodulatory activity. However, the specific impact of PC on immunomodulation, particularly its effect on dendritic cells (DCs), remains unknown. DCs act professionally as antigen-presenting cells that trigger adaptive immune responses, making them critical for immunomodulation., Materials and Methods: The DCs derived from mouse bone marrow were used to examine the suppressive effect of PC extract on DC activation and maturation. The in vivo suppressive effect was evaluated using a mouse model of contact hypersensitivity (CHS) responses. The determination of the substances in the sample was performed by Liquid chromatography-mass spectrometry/mass spectrometry., Results: The ethyl acetate extract of PC (PCEA) significantly decreased the expressions of proinflammatory cytokines (IL-12, interleukin [IL]-6, as well as tumor necrosis factor [TNF]-α) and surface markers CD80 and CD86 in lipopolysaccharide-stimulated DCs. In the 2,4-dinitro-1-fluorobenzene-induced CHS mouse model, PCEA treatment dramatically attenuated the severity of symptoms. This was evidenced by the alleviation of ear swelling and a reduction in the count of infiltrating CD3 + T cells in the tested ears. In addition, N-acetyldopamine dimer and trimer were identified as major components., Conclusion: This study is the first to show that components derived from PCEA inhibit the activation and maturation of DCs as well as CHS responses, indicating they have the potential for treating delayed-type hypersensitivity or DC-related immune disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study., Method: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR)., Results: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148 ng/mL for MeP, 38.8 vs. 13.6 ng/mL for EtP, 117 vs. 57.7 ng/mL for PrP, and 6.61 vs. 2.79 ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (β = 0.580) and a positive association of BUN (β = 0.061) and a negative association of eGFR (β = -0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T 3 ) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T 2 ) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality., Conclusion: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Previous studies have suggested a possible association between carbon monoxide poisoning (COP) and hypothyroidism, but the evidence is limited. Therefore, the aim of this study was to further investigate this relationship. Using data from the Taiwan National Health Research Database, we identified 32,162 COP patients and matched with 96,486 non-COP patients by age and index date for an epidemiological study. The risk of hypothyroidism was compared between the two cohorts until 2018. Independent predictors of hypothyroidism were analyzed using competing risk analysis. An animal study was also conducted to support the findings. COP patients had an increased risk of hypothyroidism compared to non-COP patients in the overall analysis (adjusted hazard ratio [AHR]= 3.88; 95 % confidence interval [CI]: 3.27-4.60) and in stratified analyses by age, sex, and comorbidities. The increase in the overall risk persisted even after more than six years of follow-up (AHR= 4.19; 95 % CI: 3.18-5.53). Independent predictors of hypothyroidism, in addition to COP, included age ≥65 years, female sex, hyperlipidemia, and mental disorder. The animal study showed damages in the hypothalamus, pituitary gland, and thyroid, as well as altered hormone levels 28 days after COP exposure. The epidemiological results showed an increased risk of hypothyroidism in COP patients, which was further supported by the animal study. These findings suggest the need for close monitoring of thyroid function in COP patients, especially in those who are age ≥65 years, female, and have hyperlipidemia or mental disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Managing shock, a life-threatening emergency, is challenging. The influence of the initial misclassification of undifferentiated hypotension (UH) in the emergency department (ED) on patients' outcomes remains uninvestigated. The aim of this study was to investigate whether the initial misclassification of UH in the ED affects patients' clinical outcomes. Materials and Methods: This prospective observational study enrolled 270 non-traumatic adult patients with UH who had visited the ED of National Taiwan University Hospital between July 2020 and January 2022. The patients were divided into same-diagnosis and different-diagnosis groups, depending on the consistency between the initial and final classifications of shock. The outcome was survival to discharge. The clinical variables, management, and outcomes were compared between the groups. Results: A total of 39 of 270 patients (14.4%) were in the different-diagnosis group. Most misclassified patients were initially diagnosed as having hypovolemic shock (HS, n = 29) but finally diagnosed as having distributive shock (DS, n = 28) or cardiogenic shock ( n = 1). When compared with the same-diagnosis group, the different-diagnosis group had higher hospitalization (94.9% vs. 81.4%, p = 0.023) but lower ED discharge (5.1% vs. 16.5%, p = 0.046) rates. Logistic regression analysis showed that the HS initially diagnosed was associated with an increased risk of misclassification (odds ratio [OR] = 14.731, 95% confidence interval [CI] = 3.572-60.749, p < 0.001). However, the survival to discharge did not differ between the two groups. DS, when finally diagnosed instead of the initial misclassification, was associated with in-hospital mortality (OR = 0.317, 95%CI = 0.124-0.810, p = 0.016). Conclusions: The misclassification of UH in the ED is not rare, particularly in patients with DS, who are likely to be initially misdiagnosed with HS. Although misclassification may increase hospitalization and decrease ED discharge, it does not affect survival to discharge.

As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD., Competing Interests: All the authors declare no conflict of interest.

Air insoles have provided insights for reducing the risk of diabetic foot ulcers (DFU). The pressure time integral (PTI) is an effective assessment that considers the time effect in various physical activities. We investigated the interactions between three different insole inner pressures (80, 160, and 240 mmHg) and two walking durations (10 and 20 min). The big toe (T1), first metatarsal head (M1), and second metatarsal head (M2) were investigated in 13 healthy participants. One-way analysis of variance (ANOVA) showed that the effects of each insole inner pressure significantly differed (P < 0.05) with a 10 min walking duration. The PTI values resulting from 80 mmHg in M2 (38.4 ± 3.8, P = 0.002) and 160 mmHg in M1 (44.3 ± 4.3, P = 0.027) were lower than those from 240 mmHg. Additionally, the paired t test showed that the effects of each walking duration were also considerably different at 160 mmHg. The PTI at 10 min was lower than that at 20 min in M1 (44.31 ± 4.31, P = 0.015) and M2 (47.14 ± 5.27, P = 0.047). Thus, we suggest that walking with a pressure of 160 mmHg for 10 min has a lower risk of DFU., (© 2024. The Author(s).)

Background: The survival trend and factors influencing short- and mid-term mortality in Asian out-of-hospital cardiac arrest (OHCA) survivors should be elucidated. We performed survival analyses on days 3 and 30, hypothesizing decreased survival rates within the initial 3 days post-resuscitation. Additionally, variables linked to mortality at these two timepoints were examined., Methods: We performed a retrospective analysis on adult nontraumatic OHCA survivors admitted to the National Taiwan University Hospital and its branches between 2017 and 2021. We collected the following variables from the NTUH-Integrative Medical Database: basic characteristics, cardiopulmonary resuscitation events, inotrope administration, and post-resuscitation management. The outcomes included 3- and 30-day mortality. Subgroup analyses with the Kaplan-Meier method explored the survival probability of the OHCA survivors and assessed differences in cumulative survival among subgroups. Cox proportional hazards model was used to estimate adjusted hazard ratios with 95% confidence interval., Results: Of the 967 survivors, 273 (28.2%) and 604 (62.5%) died within 3 and 30 days, respectively. The 30-day survival curve after OHCA showed an uneven decline, with the most significant decrease within the first 3 days of admission. Various risk factors influence mortality at 3- and 30-day intervals. Although increased age, noncardiac etiology, and prolonged low-flow time increased mortality risks, bystander CPR, targeted temperature management, and continuous renal replacement therapy were associated with reduced mortality at 3- and 30-day timeframes., Conclusion: Survival declined in most OHCA survivors within 3 days post-resuscitation. The risk factors associated with mortality at 3- and 30-day intervals varied in this population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Aims: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants., Methods and Results: We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post-Acute-Care (HF-PAC) programme. Participants completed the EuroQol-5 dimension (EQ-5D) questionnaire, the EQ-5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ-5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR-QoL measurements and determinants. Average scores for EQ-5D, MLHFQ, EQ-5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ-5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ-5D VAS with chronic kidney disease; and MLHFQ with age., Conclusions: This study illuminates the variance in HR-QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient-centred care. However, for a more precise HR-QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ-5D-derived utility scores might be necessary, emphasizing the importance of patient-specific considerations within the HF-PAC programme., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation., Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness., Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P  = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings., Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Huang, Yang, Toh, Chang, Su, Lin, Wang, Wang and Liao.)

Background: Patients with chronic kidney disease (CKD) experience atrial fibrillation more frequently. The balance of medical management for stroke prevention and bleeding events presents a challenging issue in CKD population. Left atrial appendage occlusion (LAAO) may be an effective solution for stroke prevention in patients who experience frequent bleeding with oral anticoagulants. However, the specific impact of CKD on the procedural success, complications, and outcomes of LAAO implantations remains underexplored., Methods: We conducted a search of various databases for articles published before October 31, 2023. This search yielded 7 studies, comparing outcomes between CKD and non-CKD cohorts undergoing LAAO implantation. Our analysis focused on CHA2DS2-VASc scores, average eGFR, use of oral anticoagulants, procedural success rates, procedural complications, and associated outcomes., Results: The meta-analysis included data from 2576 patients, with 1131 identified as having CKD. The CKD group also had higher CHA2DS2-VASc scores (4.7 ± 1.4 vs 4.0 ± 1.5; P < .001) and HAS-BLED scores (3.8 ± 1.1 vs 3.1 ± 1.0; P < .001) than the non-CKD group. CKD patients showed a nonreduction in procedural success rates and a nonsignificant increase in total complications. The risks of stroke and transient ischemic attack, major bleeding, and cardiovascular mortality were not significantly different between the 2 groups. However, a significantly lower rate of total mortality was observed in the non-CKD group (odds ratio: 0.43; 95% confidence interval, 0.32-0.60)., Conclusion: While CKD is associated with a nonsignificant decrease in procedural success and a nonsignificant increase in complication risks, the outcomes of LAAO implantation are comparably favorable between CKD and non-CKD groups. Despite similar procedural outcomes, the CKD group exhibited a higher rate of all-cause mortality., Competing Interests: The authors have no funding and conflicts of interest to disclose. The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Phosphorylated Tau (p-Tau), an early biomarker of neuronal damage, has emerged as a promising candidate for predicting neurological outcomes in cardiac arrest (CA) survivors. Despite its potential, the correlation of p-Tau with other clinical indicators remains underexplored. This study assesses the predictive capability of p-Tau and its effectiveness when used in conjunction with other predictors., Methods: In this single-center retrospective study, 230 CA survivors had plasma and brain computed tomography scans collected within 24 h after the return of spontaneous circulation (ROSC) from January 2016 to June 2023. The patients with prearrest Cerebral Performance Category scores ≥ 3 were excluded (n = 33). The neurological outcomes at discharge with Cerebral Performance Category scores 1-2 indicated favorable outcomes. Plasma p-Tau levels were measured using an enzyme-linked immunosorbent assay, diastolic blood pressure (DBP) was recorded after ROSC, and the gray-to-white matter ratio (GWR) was calculated from brain computed tomography scans within 24 h after ROSC., Results: Of 197 patients enrolled in the study, 54 (27.4%) had favorable outcomes. Regression analysis showed that higher p-Tau levels correlated with unfavorable neurological outcomes. The levels of p-Tau were significantly correlated with DBP and GWR. For p-Tau to differentiate between neurological outcomes, an optimal cutoff of 456 pg/mL yielded an area under the receiver operating characteristic curve of 0.71. Combining p-Tau, GWR, and DBP improved predictive accuracy (area under the receiver operating characteristic curve = 0.80 vs. 0.71, p = 0.008)., Conclusions: Plasma p-Tau levels measured within 24 h following ROSC, particularly when combined with GWR and DBP, may serve as a promising biomarker of neurological outcomes in CA survivors, with higher levels predicting unfavorable outcomes., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

With the global whisky market reaching $65.6 billion in 2024 and projected to reach $89.48 billion by the end of 2029, the incentives for fraud in relation to (and adulteration of) this alcoholic beverage are self-evident. Law enforcement agencies worldwide have taken actions against crimes of this nature, with forensic scientists playing crucial roles (mainly through expert testimonies on sample authenticities) during legal proceedings. Important issues associated with Scotch whisky authentication include: (a) understanding the typical manufacturing process; (b) acquisition of reference samples; and (c) effective utilization of instrumentations to characterize features derived from the manufacturing process and strategic approaches for the interpretation of analytical findings. Following a brief review of the definition/classification, manufacturing, and adulteration/counterfeiting of Scotch whiskies, this review focuses on the characterization of manufacturing-derived features and interpretation of analytical findings as grouped into: (a) quantitative analysis of single compounds; (b) qualitative analysis and intensity ratio of multiple compounds; (c) chemometric analysis of selected multi-compounds; and (d) quantitative analysis of selected elements. Finally, a flowchart for conducting the authentication process, from various significantly different perspectives, is proposed., (Copyright © 2024 Forensic Science Review.)

Background: Prehospital electrocardiogram (PHECG) shortens door-to-balloon time in patients with ST-elevation myocardial infarction. However, it may increase the prehospital service time, thus offsetting the benefits gained. The performance of PHECG could be influenced by the proficiency of the emergency medical technicians (EMTs)., Objectives: To investigate whether there are differences in the performance of PHECG between EMT-II and EMT-paramedics (EMT-P)., Methods: This prospectively designed, retrospectively analyzed study of PHECG was conducted in Taipei from February 2019 to April 2021. Comparisons were made between EMT-II and EMT-P teams. The primary outcomes were the acceptance of PHECG suggestions and prehospital service time. The secondary outcomes were gender disparities in the primary outcomes., Results: A total of 2,991 patients were included, of whom 2,617 received PHECG. For the primary outcomes, the acceptance of PHECG was higher in those approached by EMT-P (99.6% vs. 71.5%, p < 0.001). The scene time and scene-to-hospital time showed no significant differences. For gender disparities, the acceptance of PHECG in female patients was significantly lower in those approached by EMT-II (59.3% vs. 99.2%, p < 0.001). The scene time and scene-to-hospital time were generally longer in the female patients, especially in the younger and middle age groups. Compared to EMT-P, both were significantly longer in the female patients approached by EMT-II., Conclusions: The acceptance of PHECG was lower in those approached by EMT-II, especially in females. Although there were generally no significant differences between EMT-II and EMT-P, the scene time and scene-to-hospital time were significantly longer in female patients, especially in those aged < 75 years approached by EMT-II., Competing Interests: All the authors declare no conflict of interest.

Background: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown., Materials and Methods: In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified., Results: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR., Conclusions: A high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

A high mortality rate makes hepatocellular carcinoma (HCC) a difficult cancer to treat. When surgery is not possible, liver cancer patients are treated with chemotherapy. However, HCC management and treatment are difficult. Sorafenib, which is a first-line treatment for hepatocellular carcinoma, initially slows disease progression. However, sorafenib resistance limits patient survival. Recent studies have linked HCC to programmed cell death, which has increased researcher interest in therapies targeting cell death. Pyroptosis, which is an inflammatory mode of programmed cell death, may be targeted to treat HCC. Pyroptosis pathways, executors, and effects are examined in this paper. This review summarizes how pyroptosis affects the tumor microenvironment (TME) in HCC, including the role of cytokines such as IL-1β and IL-18 in regulating immune responses. The use of chemotherapies and their ability to induce cancer cell pyroptosis as alternative treatments and combining them with other drugs to reduce side effects is also discussed. In conclusion, we highlight the potential of inducing pyroptosis to treat HCC and suggest ways to improve patient outcomes. Studies on cancer cell pyroptosis may lead to new HCC treatments., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models., Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan., Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68-0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53-2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60-2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63-6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group., Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)