Tzu Chi Medical Journal最新文献

Objectives: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a glycophosphatidylinositol-anchored member of the immunoglobulin superfamily, often overexpressed in various malignancies. Targeting CEACAM6 by suppressing its expression can potentially reverse these effects, making it a promising therapeutic target. In this study, we generated five monoclonal antibodies (CEAS1, CEAS2, CEAS3, CEAS4, and CEAS5; CEAS1-S5) against the recombinant CEACAM6 protein.

Materials and methods: Through enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay, we demonstrated that each antibody specifically binds to CEACAM6 without interfering with the binding of others. SPR analysis further revealed the rate of association (K_a), dissociation (K_d), and equilibrium dissociation constants (K_D) for each antibody.

Results: The K_D values ranged from 5.089 × 10^-11 to 1.213 × 10^-13 M, with CEAS5 exhibiting the highest binding affinity. In addition, CEAS5, unlike CEAS1-S4, could bind to both CEACAM5 and CEACAM6, indicating its bivalent nature.

Conclusion: These findings highlight the strong antigen-binding capabilities of CEAS1-S5, warranting further investigation.

Objectives: Coronavirus disease 2019 (COVID-19) is associated with poor cardiac outcomes and an increased risk of long-term cardiovascular disease. Long-term cardiovascular outcomes among patients with COVID-19 after exercise-based cardiac rehabilitation remain largely unknown. This study aimed to investigate the long-term cardiovascular outcomes of COVID-19 survivors after exercise-based cardiac rehabilitation using real-world data.

Materials and methods: We analyzed the data from the US Collaborative Network of the TriNetX Research Database. Adults aged ≥18 years who were diagnosed with COVID-19 between 2020 and 2022 were enrolled in this study. The comparison comprised a cohort of patients receiving exercise-based cardiac rehabilitation and 1:1 propensity score-matched controls.

Results: The exercise-based cardiac rehabilitation group was found to have lower risks of developing several long-term cardiovascular outcomes than the controls, such as mortality (hazard ratio [HR] = 0.75 [0.63-0.89]), stroke (HR = 0.81 [0.68-0.94]), myocardial infarction (HR = 0.75 [0.61-0.89]), ischemic cardiomyopathy (HR = 0.86 [0.75-0.99]), heart failure (HR = 0.73 [0.65-0.83]), and nonischemic cardiomyopathy (HR = 0.78 [0.63-0.92]).

Conclusion: Among COVID-19 survivors, those undergoing cardiac rehabilitation had lower risks of cardiovascular outcomes, including mortality, stroke, myocardial infarction, ischemic cardiomyopathy, heart failure, and nonischemic cardiomyopathy, than those of controls.

Objectives: The objective is to evaluate the protective effects of six coumarin derivatives against peroxide-induced cardiomyocyte damage and investigate their action mechanisms.

Materials and methods: Intracellular reactive oxygen species and mitochondrial membrane potential (MMP) were analyzed using dihydrorhodamine 123 and JC-1 combined with flow cytometry. Cell viability and apoptosis were assessed using WST-1 and lactate dehydrogenase analysis kits, respectively. The apoptotic signaling pathway was analyzed using a mouse apoptosis array kit. Cellular protein expression was detected using Western blotting.

Results: Among the six coumarin derivatives tested, only 7-hydroxyflavone demonstrated the ability to protect cardiomyocytes from hydrogen peroxide (H₂O₂)-induced damage. Protein expression analysis revealed that 7-hydroxyflavone reduced cytochrome c release from the mitochondria and inhibited H₂O₂-induced activation of caspase-3. In addition, 7-hydroxyflavone maintained MMP stability in cardiomyocytes exposed to H₂O₂.

Conclusion: 7-hydroxyflavone has potential as an effective antioxidant supplement for cardiac tissues. Further research is required to elucidate its pharmacokinetics and metabolic profile in humans to facilitate its therapeutic application.

Objectives: The objective of the study is to understand the prevalence of bacterial co-infection and secondary infection in severe coronavirus disease 2019 (COVID-19) pneumonia in a tertiary hospital intensive care unit (ICU), the spectrum of pathogens, and the impact of these infections on clinical outcomes.

Materials and methods: Retrospective analysis of all patients with COVID-19 with acute hypoxemic respiratory failure who were admitted to the ICU requiring invasive mechanical ventilation (IMV) or high-flow nasal cannula (HFNC) from January 2021 to August 2022.

Results: Of the 123 cases, 59.3% had culture-confirmed bacterial co-infection, mostly lower respiratory tract infections (LRTIs). Patients with bacterial co-infection had higher 30-day mortality (28.8% vs. 12%, hazard ratio [HR] = 2.96, %95 confidence interval [CI] =1.1-7.99; adjusted HR [aHR] = 1.34, %95 CI = 0.43-4.17). Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa were the most common co-infection pathogens. Of the 108 cases who stayed in the ICU for >2 days, 34 (31.5%) cases developed secondary bacterial infections within 30 days, of whom all cases had LRTI, 4 had bacteremia, and 8 had urinary tract infections. IMV users had a higher 1-month incidence of secondary bacterial infections than HFNC users (47.5% vs. 8.9%, P < 0.0001). Patients with secondary bacterial infections had higher 60-day mortality (32.4% vs. 11.2% HR = 3.45, 95% CI = 1.27-9.4; aHR = 2.29, %95 CI =0.8-6.67). The most common secondary infection pathogens were Acinetobacter species, P. aeruginosa, Stenotrophomonas maltophilia, and K. pneumoniae. At the 30-day follow-up, 54 events of ICU-acquired secondary bacterial LRTI were noted in 34 patients, 18 (33.3%) events, and 15 (44%) patients were infected by carbapenem-resistant Gram-negative bacilli.

Conclusion: The high incidence of bacterial co-infection and secondary infection in critically ill patients with COVID-19 might associated with increased mortality. Infection by drug-resistant pathogens may develop during the treatment course.

Objectives: Cervical cancer remains a leading cause of death among women globally, with surgery being a key treatment for early-stage disease. However, the survival outcomes (disease-free survival [DFS] and overall survival [OS]) of patients with early-stage cervical cancer treated using different surgical methods remain controversial. This systematic review and meta-analysis aimed to evaluate the survival outcomes of laparoscopic radical hysterectomy (LRH) versus open radical hysterectomy (ORH) for treating early-stage cervical cancer (tumor ≤2 cm).

Materials and methods: A comprehensive search of the PubMed, Web of Science, and Cochrane databases from 1960 to 2022 identified 12 retrospective cohort studies for inclusion. The primary outcome included DFS and OS. The pooled hazard ratio (HR) with 95% confidence intervals (CI) was calculated to compare DFS and OS. The I ² statistic was used to estimate the heterogeneity of the included studies. A funnel plot was used to examine publication bias. Review Manager version 5.4 software was used for the analysis. P < 0.05 was statistically significant.

Results: The results showed no significant difference between LRH and ORH in a 5-year OS (HR = 1.25; 95% CI, 0.82-1.86; P = 0.3) or 5-year DFS (HR = 1.03; 95% CI, 0.67-1.57; P = 0.9), with minimal publication bias in DFS.

Conclusion: LRH is a safe and effective alternative to ORH for early-stage cervical cancer, with similar survival outcomes. The results may encourage further research into optimizing minimally invasive techniques, potentially influencing the clinical guidelines and promoting the broader adoption of LRH in treating cervical cancer.

Objectives: Pooling can reduce reverse transcriptase polymerase chain reaction (RT-PCR) tests during the coronavirus disease-19 (COVID-19) pandemic. Pooling strategy is a complex issue. Recent advances in computer science may provide a better strategy.

Materials and methods: We developed our algorithm which can help healthcare workers set up their pooling policy during the COVID-19 pandemic.

Results: Comparing with three other strategies, naming single pooling, array pooling, and hypercube pooling, our multiple pooling shows to be the best with minimal RT-PCR tests per patient.

Conclusion: We hope clinicians in COVID-19 pandemic regions can use our algorithm to reduce both RT-PCR tests and time and hence save more lives.

Objectives: Transplantation of human umbilical cord blood cells (hUCB) may enhance neuroprotection, and thus, the intravenous (IV) infusion of hUCB in patients with acute ischemic stroke (AIS) is being tested for its safety and efficacy.

Materials and methods: We conducted a 12-month, open-label, and single-center, phase I trial of hUCB treatment in AIS patients at the age of 45-80 years, with magnetic resonance imaging evidence of acute infarction in the internal carotid artery supplied territory and the National Institute of Health Stroke Scale (NIHSS) score between 6 and 18. Eligible participants received a single-dose IV infusion of hUCB followed by the two doses of mannitol infusion within 9 days after the onset of stroke symptoms. The primary endpoint was the incidence of adverse events (AEs) and the secondary endpoints were the changes in NIHSS, Barthel index (BI), and Berg Balance Scale (BBS) scores.

Results: Six patients (Male: Female = 3: 3) were enrolled with a mean age at 65.8 years. A total of 40 AEs occurred in six participants during this study, which included nine serious adverse events. Only transient erythema multiforme and hematuria were probably and possibly related to hUCB infusion, respectively. The mean NIHSS score was 11.5 at baseline and it significantly improved at 1, 3, 6, 9, and 12 months after treatment (mean change from baseline: -4.0, -5.3, -6.8, -7.0, and -7.3). The mean BI score was 22.5 at baseline and it significantly increased at 3 and 6 months after treatment (mean change from baseline: 26.7 and 42.5, respectively). The BBS score increased numerically but did not reach statistical significance. The changes in cytokine levels and spleen size were unremarkable.

Conclusion: The IV hUCB was safe and well tolerated in AIS patients, and the preliminary efficacy results demonstrated its therapeutic potential, supporting the conduct of a randomized, placebo controlled, phase II clinical trial in future.

Therapeutic peptides have become an intensively anticipated research field for novel drug discovery and design owing to their high specificity, efficacy, and biocompatibility. The advances in computer technology and structural biology, together with the invention of chemical peptide synthesis methods, have led to tremendous progress in this research field. Over the years, more than 100 peptide-based therapeutics have been approved for clinical use, and many others are currently under clinical trials. However, the in vivo application of therapeutic peptides is hindered by intrinsic disadvantages of peptides, such as poor stability against enzymatic degradations, short in vivo half-life, and low oral bioavailability. Therefore, strategies for efficiently protecting the peptides inside the body and facilitating the delivery of peptides to their targets are required. Lipid-based nanoparticles are considered a versatile class of carriers for drug delivery. Their biocompatibility, biodegradability, and ability to interact with biological membranes make them ideal platforms for in vivo delivery of peptides. Here, by leveraging examples, we aim to provide a comprehensive review of the current status of therapeutic peptide developments and lipid-based nanoparticles as drug carriers. Recent attempts to utilize lipid-based nanoparticles as platforms for the oral delivery of therapeutic peptides are also discussed.

Uremic toxins (UTs) are bioactive compounds that accumulate in chronic kidney disease (CKD) due to impaired renal clearance, exacerbating disease progression and cardiovascular (CV) complications. These toxins originate from endogenous metabolism, gut microbiota, and dietary intake and include protein-bound UTs such as p-cresyl sulfate, indoxyl sulfate, and indole acetic acid, as well as small, water-soluble toxins such as trimethylamine-N-oxide and phenylacetylglutamine. Their accumulation promotes oxidative stress, inflammation, and endothelial dysfunction, contributing to vascular damage and associated with CV risk. Current management strategies focus on dietary interventions, prebiotics, probiotics, oral sorbents, emerging pharmacological approaches, and advanced dialysis techniques, but clinical outcomes remain inconsistent. Recent trials have demonstrated the potential of agents such as sevelamer, high-amylose-resistant starch, and AST-120 to reduce UT levels and improve certain vascular markers. However, more robust, long-term studies are necessary to fully establish the therapeutic efficacy and optimize treatment strategies to mitigate the impact of gut-derived UTs on CKD and CV health.

Chronic Achilles tendon rupture (CATR) represents a significant clinical challenge, often necessitating surgical intervention to restore function, alleviate pain, and prevent long-term complications. The complex nature of CATR, characterized by tendon retraction, scar formation, and poor tissue quality, requires a tailored, evidence-based approach. This review comprehensively examines current surgical strategies for managing CATR, focusing on their indications, advantages, outcomes, and associated complications. A detailed literature search of 20 studies published between 2010 and 2023 identified key surgical techniques, including end-to-end repair, tendon transfers, autografts, synthetic grafts, and allografts. Surgical recommendations were stratified by defect size and patient factors. Small defects (<2 cm) are effectively managed with end-to-end repair or tendon transfers, offering rapid recovery and restoration of tendon continuity. Medium defects (2-5 cm) benefit from techniques such as V-Y plasty or semitendinosus autografts, providing additional length and biomechanical stability. Larger defects (>5 cm) often necessitate advanced procedures, including free tendon grafts, synthetic materials, or allografts, particularly for older patients or those with poor tissue quality. Minimally invasive techniques, such as endoscopic flexor hallucis longus transfer, have shown promise in reducing recovery times and complications. A structured decision-making framework is proposed to guide surgical choices, ensuring patient-specific, optimal outcomes. Emerging techniques further expand the possibilities for managing this challenging condition, emphasizing the need for innovation and individualized care in CATR treatment.