Tzu Chi Medical Journal最新文献

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to the accumulation of LDL cholesterol (LDL-C) in the bloodstream, resulting in hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing the expression level or inducing the activity of LDLR in hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced in the liver, promotes the degradation of LDLR. Inhibiting the expression and/or function of PCSK9 can increase the levels of LDLR on the surface of hepatocytes and promote LDL-C clearance from the plasma. Thus, targeting PCSK9 represents a new strategy for developing preventive and therapeutic interventions for hypercholesterolemia. Currently, monoclonal antibodies are used as PCSK9 inhibitors in clinical practice. However, the need for oral and affordable anti-PCSK9 medications limits the perspective of choosing PCSK9 inhibitors for clinical usage. Emerging research reports have demonstrated that natural phytochemicals have efficacy in maintaining cholesterol stability and regulating lipid metabolism. Developing novel natural phytochemical PCSK9 inhibitors can serve as a starting point for developing small-molecule drugs to reduce plasma LDL-C levels in patients. In this review, we summarize the current literature on the critical role of PCSK9 in controlling LDLR degradation and hypercholesterolemia, and we discuss the results of studies attempting to develop PCSK9 inhibitors, with an emphasis on the inhibitory effects of natural phytochemicals on PCSK9. Furthermore, we provide insight into the mechanisms of action by which the reported phytochemicals exert their potential PCSK9 inhibitory effects against hypercholesterolemia.

Inflammation and stem cell mobilization or homing play pivotal roles in tissue repair and regeneration. This review explores their intricate interplay, elucidating their collaborative role in maintaining tissue homeostasis and responding to injury or disease. While examining the fundamentals of stem cells, we detail the mechanisms underlying inflammation, including immune cell recruitment and inflammatory mediator release, highlighting their self-renewal and differentiation capabilities. Central to our exploration is the modulation of hematopoietic stem cell behavior by inflammatory cues, driving their mobilization from the bone marrow niche into circulation. Key cytokines, chemokines, growth factors, and autophagy, an intracellular catabolic mechanism involved in this process, are discussed alongside their clinical relevance. Furthermore, mesenchymal stem cell homing in response to inflammation contributes to tissue repair processes. In addition, we discuss stem cell resilience in the face of inflammatory challenges. Moreover, we examine the reciprocal influence of stem cells on the inflammatory milieu, shaping immune responses and tissue repair. We underscore the potential of targeting inflammation-induced stem cell mobilization for regenerative therapies through extensive literature analysis and clinical insights. By unraveling the complex interplay between inflammation and stem cells, this review advances our understanding of tissue repair mechanisms and offers promising avenues for clinical translation in regenerative medicine.

Radiotherapy (RT) is one of the primary treatment modalities in managing cancer patients. Recently, combined RT and immunotherapy (IT) (i.e., radio-IT [RIT]) have been aggressively investigated in managing cancer patients. However, several issues in conducting RIT are challenging, such as incorporating advanced irradiation techniques, predictive/prognostic biomarkers, and other treatment modalities. Several clinical efforts and novel biomarkers have been introduced and developed to solve these challenges. For example, stereotactic radiosurgery/stereotactic radiotherapy, stereotactic body radiotherapy/stereotactic ablative body radiotherapy, and FLASH-RT have been applied for delivering precise irradiation to lung and liver tumors in conjunction with IT. Besides, several novel IT agents and incorporations of other therapies, such as targeted and thermal therapies, have been further investigated. The present study reviewed the emerging challenges of RIT in modern oncology. We also evaluated clinical practice, bench research, and multimodality treatments. In addition to several clinically applicable biomarkers, we emphasize the roles of advanced irradiation techniques and epigenetic modification as predictive/prognostic biomarkers and potential therapeutic targets. For example, 6(m) A-based epigenetic agents demonstrate the potential to enhance the treatment effects of RIT. However, further prospective randomized trials should be conducted to confirm their roles.

Cardiovascular diseases (CVDs) are major contributors to illness and death globally. Body mass index (BMI) is a well-established prognostic factor on cardiovascular risk outcome. Numerous investigations have provided evidence for the existence of the obesity paradox after percutaneous coronary intervention (PCI). However, the association between BMI and the results following PCI has not been extensively investigated in Asian populations. The research aims to fill the current void in understanding by investigating the association between BMI and clinical consequences following PCI, with a particular focus on Asian individuals. A systematic search was conducted through PubMed, ScienceDirect, and Cochrane Library to identify studies examining the effect of BMI on clinical outcome after PCI in Asia. R Studio 4.3.2 software was used to carry out the analysis of the data. A total of 182,110 patients who had gone through PCI were found in the 5 included cohorts. A meta-analysis conducted on the subjects revealed that patients who were overweight (odds ratio [OR] = 0.60, 95% confidence interval [CI] [0.57, 0.63], P < 0.0001) had a lower risk of all-cause mortality compared to individuals with a healthy weight and patients with obesity (OR = 0.65, 95% CI [0.41, 1.05], P = 0.006) had a lower risk of all-cause mortality than healthy weight individuals. The study also found that overweight patients (OR = 0.60, 95% CI [0.39, 0.91], P = 0.02) had a lower risk of cardiac mortality. In addition, obese patients (OR = 0.41, 95% CI [0.19, 0.88], P = 0.02) had a lower risk of noncardiac mortality. However, the study found that there were no differences in major adverse cardiovascular event, myocardial infarction, and bleeding between all patient groups. This meta-analysis supports the presence of an obesity paradox after PCI in Asian populations. The obesity paradox was evident in all-cause mortality, cardiac mortality, and noncardiac mortality.

Nocturia is defined as the nocturnal frequency of one or more voiding episodes per night. It increases with aging and has an impact on sleep quality and the risks of falling and mortality. Nocturia disorder involves nighttime frequency, nocturnal polyuria, and nocturnal enuresis. In older adults with nocturia disorder, multiple factors could contribute to nocturia severity and characteristics, including poor sleep quality, lower urinary tract dysfunction, and excessive fluid output. Several nonurological medical diseases have been found to result in nocturia, such as hypertension, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease, metabolic syndrome, and diabetes. Urological and medical assessments should be performed to diagnose nocturia disorder. A frequency volume chart to evaluate the nocturnal polyuria index, functional bladder capacity, and urodynamic study can reveal the presence of nocturnal polyuria and lower urinary tract dysfunction. Treatment should be based on multiple nocturia etiologies, and a combination of multiple therapies for individual pathophysiology will achieve a better treatment outcome.

Periprosthetic joint infection (PJI) is a significant issue in orthopedic surgery. Urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) have been identified as potential causes of PJI; however, evidence is inconclusive. Understanding these relationships is critical for improving therapy and patient outcomes. A systematic review was performed by conducting searches from PubMed, EBSCO, ProQuest, and manual searching with adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 guideline. Studies that reported UTI/ASB and PJI were included. Meta-analysis was conducted using a random-effects model using RevMan 5.4 software. A total of 14 studies were included with UTIs and ASB showed an overall association with increased risk of PJI (odds ratio [OR]: 1.84, 95% confidence interval [CI]: 1.14-2.99, P = 0.01). However, subgroup analysis for UTIs and ASB was not significant. Further analysis of UTIs in total hip arthroplasty (THA) surgery showed a significant association (OR: 1.76, 95% CI: 1.57-1.96) with PJI. Preoperative UTIs timing between 0 and 2 weeks before surgery showed an increased risk of PJI (OR: 1.45, 95% CI: 1.35-1.55). Antibiotic treatment in ASB did not significantly impact PJI rates. Urine and PJI sample cultures in four studies showed no correlation of microorganisms between the two sites. According to recent evidence, a statistically significant association was found between UTIs and PJI in patients who underwent THA surgery. However, ASB did not yield significant results in relation to PJI. These results should be supported by larger and well-designed studies to make proper clinical suggestion in future. For further research, it is recommended to adopt standardized criteria for outcome measurement and to involve larger sample sizes to enhance the reliability and generalizability of findings.

Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies. The structures of CXCL12 and CXCR4 have been resolved with experimental methods such as X-ray crystallography, NMR, or cryo-EM. Therefore, it is possible to apply structure-based computational approaches to discover, design, and modify therapeutic molecules for cancer treatments. Here, we summarize the current understanding of the roles played by the CXCL12-CXCR4 signaling axis in cellular functions linking to cancer progression and metastasis. This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.

Extracellular vesicles (EVs) have emerged as key players in intercellular communication, disease pathology, and therapeutic innovation. Initially overlooked as cellular debris, EVs are now recognized as vital mediators of cell-to-cell communication, ferrying a cargo of proteins, nucleic acids, and lipids, providing cellular resilience in response to stresses. This review provides a comprehensive overview of EVs, focusing on their role as biomarkers in disease diagnosis, their functional significance in physiological and pathological processes, and the potential of bioengineering for therapeutic applications. EVs offer a promising avenue for noninvasive disease diagnosis and monitoring, reflecting the physiological state of originating cells. Their diagnostic potential spans a spectrum of diseases, including cancer, cardiovascular disorders, neurodegenerative diseases, and infectious diseases. Moreover, their presence in bodily fluids such as blood, urine, and cerebrospinal fluid enhances their diagnostic utility, presenting advantages over traditional methods. Beyond diagnostics, EVs mediate crucial roles in intercellular communication, facilitating the transfer of bioactive molecules between cells. This communication modulates various physiological processes such as tissue regeneration, immune modulation, and neuronal communication. Dysregulation of EV-mediated communication is implicated in diseases such as cancer, immune disorders, and neurodegenerative diseases, highlighting their therapeutic potential. Bioengineering techniques offer avenues for manipulating EVs for therapeutic applications, from isolation and purification to engineering cargo and targeted delivery systems. These approaches hold promise for developing novel therapeutics tailored to specific diseases, revolutionizing personalized medicine. However, challenges such as standardization, scalability, and regulatory approval need addressing for successful clinical translation. Overall, EVs represent a dynamic frontier in biomedical research with vast potential for diagnostics, therapeutics, and personalized medicine.

Objectives: Discectomy is the most common surgery for lumbar herniated intervertebral disc (HIVD) disease. However, 5%-24% of patients undergo a second surgery due to recurrent disc herniation.

Materials and methods: This study was aimed to identify the risk factors for reoperation after discectomy of lumbar HIVD and recommend treatment for patients with a high risk of reoperation. We recruited patients diagnosed as having single-level lumbar HIVD who underwent open discectomy from January 1, 2000, to December 31, 2012 in our hospital. We used a survival curve to inspect the survival time and reoperation rate after surgery. We discussed the correlation of reoperation rate with discectomy level, body mass index, heavy lifting after surgery, sex, and age. Furthermore, we investigated the correlation between the experience of a surgeon and the reoperation rate.

Results: A total of 619 patients were enrolled in our study. Most patients were 40-60 years old (48.8%), and most of them had herniation at L4/5 level (48.9%). The 8-year survival rate was 92%. Weight lifting after surgery may increase the reoperation rate by 115 and 18 times for those >60 years and <40 years, respectively. In addition, less experience of the surgeon and female sex had a high reoperation rate.

Conclusion: Postoperative working modification may be very important for preventing patients from recurrent HIVD. For elderly people with HIVD, a more conservative therapy could be selected. If patients with lumbar spine hypermobility or severe degeneration require wide laminectomy, primary fusion should be considered.

Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV.

Materials and methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale.

Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy.

Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.