Tzu Chi Medical Journal最新文献

Ovulation is a complex biological process essential for female fertility, driven by the luteinizing hormone (LH) surge and involving a cascade of molecular events that lead to follicular rupture and oocyte release. This process shares characteristics with acute inflammation, including the generation of reactive oxygen species (ROS) by E2, immune cell recruitment, and tissue remodeling. E2 enhances mitochondrial ROS production through integrin-dependent signaling, regulating key ovulatory events such as cumulus expansion and extracellular matrix breakdown. The LH surge triggers follicular luteinization and progesterone production, which are critical for preparing the endometrium for implantation and modulating inflammation. Progesterone, acting through its receptor (PGR), suppresses ROS-induced inflammation by inhibiting the NF-κB pathway, ensuring controlled inflammatory responses. However, a transient decline in progesterone levels following the LH surge initiates acute inflammation, leading to follicle rupture and ovulation. This process involves the upregulation of matrix metalloproteinases and other proteases that degrade the follicular wall, facilitated by structural changes such as cumulus expansion and decellularization at the follicular apex. Post-ovulation, the remaining follicular cells undergo luteinization to form the corpus luteum, which produces progesterone to support early pregnancy. The ovulation wound heals rapidly through a process resembling ordinary wound healing where follicular fluid plays a dual role by promoting ovulation wound healing and when spilled into the pelvic cavity, potentially contributing to postoperative adhesions. Understanding the molecular mechanisms of ovulation provides valuable insights into fertility promotion, contraception development, and the prevention of reproductive disorders.

The relationship between hepatitis C virus (HCV) infection and cardiovascular disease (CVD) is increasingly recognized, with studies indicating elevated CVD prevalence and mortality among individuals with HCV. Chronic HCV patients exhibit a higher CVD risk, especially in the population of end-stage renal disease on hemodialysis. Pathogenic mechanisms may include oxidative stress, endothelial damage, metabolic dysregulation, and chronic inflammation. These factors enhance vascular damage, promoting plaque formation and instability. Direct-acting antivirals (DAAs), which have revolutionized HCV treatment by achieving sustained virologic response rates of over 95%, significantly mitigate CVD risk. DAA therapy improves endothelial function, reduces inflammatory biomarkers, and lowers the incidence of CVD events. However, lipid profiles may paradoxically increase following HCV clearance. In addition, the contrasting outcomes between DAA treatment and arrhythmia risk remain elusive. Potential epigenetic changes for CVD risk may persist after successful viral eradication. The elucidation of unmet needs is critical for solidifying screening guidelines for HCV patients with CVD and for exploration of the long-term CVD outcome in the DAA era.

Spinal surgery in patients with chronic kidney disease and end-stage renal disease on hemodialysis presents unique challenges due to systemic comorbidities, poor bone quality, and high perioperative risks. This review aims to evaluate outcomes, complications, and optimal surgical strategies in this high-risk population that reveals significantly higher rates of perioperative mortality (up to 17.2%), intensive care unit admission, and implant failure compared to nonrenal cohorts due to uremic toxicity, renal osteodystrophy, and cardiovascular vulnerabilities. Posterolateral fusion and minimally invasive techniques demonstrated advantages over interbody fusion in reducing blood loss and operative time, while circumferential stabilization improved durability in destructive cervical pathologies. Adjacent segment disease developed in 43% of lumbar fusion cases, with younger age and multilevel constructs as risk factors. Renal transplantation emerged as a protective factor, reducing complications and mortality, though access barriers persist. Despite perioperative risks, surgical intervention achieved meaningful functional improvements, including pain relief and neurological recovery. This review underscores the need for tailored surgical planning, preoperative optimization of anemia and electrolyte imbalances, and multidisciplinary care to mitigate risks. Surgeons must balance the potential benefits of spinal surgery against the substantial morbidity and mortality inherent to this population, prioritizing minimally invasive approaches and cautious patient selection.

Three-dimensional (3D) culture systems known as organoids have emerged as powerful preclinical models for human tumors, supporting the advancement of cancer research from the laboratory to clinical application. They have transformed preclinical cancer research by preserving the complexity and biological characteristics of human cancers. Organoids more accurately replicate the intricate architecture and microenvironment of clinical tumors compared to conventional in vitro cell cultures and in vivo animal models. Nonetheless, a thorough overview of the potential applications of cancer organoids is still lacking. In this review, we outline the current knowledge of cancer organoid culture. In addition, organoids and 3D cultures can accurately simulate the in vivo tumor environment. We explore the key features and underlying processes of tumor development and spread and examine recent progress in using patient-derived tumor organoids for drug testing and immunological research. In additionally, we address the existing obstacles and limitations of organoid technology in clinical settings, along with its future potential. This review underscores the promise of organoids as an innovative approach in cancer therapy and research.

Objectives: Reflux disease including gastroesophageal reflux and laryngopharyngeal reflux (LPR) is often found in obstructive sleep apnea (OSA) patients. Endoscopic examination is a gold standard diagnosis for reflux disease. However, the invasive procedure limits its widespread use. The pathophysiological characteristics of LPR are associated with refluxate components, of which pepsin is known to damage the tissues of the larynx and pharynx. Therefore, the detection of salivary pepsin to diagnose LPR becomes a potentially clinical application with noninvasiveness. In this study, we aimed to (1) validate the feasibility of salivary pepsin test for LPR in OSA patients, (2) establish the threshold of salivary pepsin in diagnosing LPR, and (3) explore the relationship between OSA and LPR.

Materials and methods: Seventy adult polysomnography-diagnosed OSA patients were enrolled. Reflux finding score (RFS) and salivary pepsin test were utilized to evaluate LPR. RFS is a set of eight objective laryngoscopic findings (total score: 0-26), with a total score of >7 as RFS-positive representing LPR-positive. The salivary pepsin concentration was detected by enzyme-linked immunosorbent assay with a standard protocol.

Results: Salivary pepsin test was performed quickly and smoothly in all subjects with no discomfort or side effects. Based on RFS positive, the prevalence of LPR was up to 86% in our study population. There is a trend that the median salivary pepsin concentration in RFS-positive patients was higher than RFS-negative patients (14.9 ng/ml vs. 7.23 ng/ml). The cutoff point (2.3 ng/ml) of salivary pepsin concentration yielded a sensitivity of 93% in the diagnosis of LPR. Neither apnea/hypopnea index nor salivary pepsin concentration was different between LPR-positive versus LPR-negative groups and nonsevere versus severe OSA groups.

Conclusion: LPR is highly prevalent in OSA patients. Salivary pepsin test could be an alternative to endoscopic findings for the diagnosis of LPR with noninvasiveness. The threshold of salivary pepsin concentration of 2.3 ng/ml offers 93% sensitivity in the diagnosis of LPR. The relationship between OSA and LPR is bidirectional and more likely to be an overlapping syndrome-combined laryngopharyngeal reflux and OSA (CLOSA). Pharmacologic therapy for LPR is needed in patients with CLOSA for comprehensive treatment.

Objectives: This study aimed to investigate the core symptom of autism in Indonesian children using Childhood Autism Rating Scale (CARS) scores and their relationship with cognitive profiles while evaluating the effectiveness of aripiprazole and behavioral intervention across different cognitive levels.

Materials and methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Bandung City, Indonesia, from February 2023 to January 2024. Participants aged 6-10 years with autism spectrum disorder (ASD) were assessed using CARS and Stanford-Binet Intelligence Scales Form L-M. They were randomized to receive either aripiprazole with behavioral therapy (BT) or placebo with BT for 12 weeks. CARS scores and cognitive levels were evaluated at baseline and after treatment.

Results: The study enrolled 51 participants (29 placebo and 22 aripiprazole). Both groups showed significant improvements in CARS and cognitive scores over 12 weeks. The aripiprazole group demonstrated greater reductions in CARS scores (5.17 points for higher-cognitive level [HC-ASD]; 4.88 points for lower-cognitive level [LC-ASD] compared to the placebo group. Significant improvements were observed in visual response, taste/smell/touch response, and fear/nervousness CARS subcategories (P < 0.05). Receiver operating characteristic analysis revealed that CARS scores at end-of-treatment (EoT) were strong predictors of cognitive improvement, with an optimal cutoff of 36.25 achieving high sensitivity and specificity (AUC 0.776, P < 0.05).

Conclusion: Early identification, accurate differentiation between LC-ASD and HC-ASD, and targeted interventions combining pharmacological treatment with BT are essential for improving outcomes in children with ASD. These approaches can reduce symptom complexity while fostering long-term functional skills development.

Objectives: Laparoscopic total extraperitoneal (TEP) hernia repair is one of the widely used surgical methods for symptomatic inguinal hernia. Although laparoscopic procedures provide advantages on postoperative complications and shorter convalescence, there is currently no global consensus on the timing for returning to work following laparoscopic hernia repair. This study compared the outcomes of early and late return to work after laparoscopic TEP inguinal hernia repair.

Materials and methods: Between March 2008 and December 2019, we reviewed 506 cases of laparoendoscopic TEP hernia repair. Among these, 231 cases where patients returned to work within 1 week postsurgery were classified as the early group, while 275 cases of patients either unemployed or returning to work after more than 1 week were classified as the late group. The primary endpoint was inguinal hernia recurrence. The secondary endpoints included postoperative chronic inguinal pain (defined as persistent pain 6 months postoperation), seroma formation, and the physical function domain of SF-36 v2.

Results: The two groups had similar baseline characteristics, except that the early return-to-work group was younger (51 ± 13.1 vs. 58.2 ± 15.9, P < 0.001) and had a lower risk of constipation before the operation (10.0% vs. 18.5%, P = 0.006). The early group did not exhibit an increased rate of inguinal hernia recurrence (1.7% vs. 2.9%, P = 0.386). In addition, the early group experienced significantly less chronic pain (4.8% vs. 11.6%, P = 0.006). There were no differences in postoperative seroma formation or scores of the physical function domain of SF-36 v2 between the early and late groups.

Conclusion: Patients who underwent laparoscopic TEP hernia repair and returned to work within 1 week did not show increased hernia recurrence rates or complications. In addition, early return to work was associated with significantly less chronic pain. Returning to work early after TEP repair is both safe and feasible. Patients are encouraged to resume work early following TEP repair.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide and is closely linked to obesity, insulin resistance, type 2 diabetes, and dyslipidemia. It ranges from simple steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis), which can progress to fibrosis, cirrhosis, or liver cancer. Beyond liver-related issues, MASLD is a systemic disease strongly associated with extrahepatic complications such as cardiovascular disease (CVD), chronic kidney disease (CKD), cancers, endocrine disorders, musculoskeletal problems, and sleep apnea. CVD and cancer are the leading causes of death in MASLD patients, with liver-related mortality ranking third. Fibrosis severity is the key predictor of overall and cause-specific mortality. MASLD significantly increases the risk and progression of type 2 diabetes, CVD, and CKD. It is also linked to increased risks of extrahepatic cancers, particularly colorectal, pancreatic, and breast cancers. Endocrine conditions such as hypothyroidism and polycystic ovary syndrome and musculoskeletal disorders, including sarcopenia and osteoporosis, frequently co-occur with MASLD. Obstructive sleep apnea independently contributes to the severity of liver disease and shares overlapping metabolic pathways. Surgical and transplant outcomes are worse in patients with MASLD due to impaired liver regeneration and increased postoperative risks. The recent approval of resmetirom offers a new therapeutic option, whereas lifestyle changes remain the cornerstone of management. Given the multisystemic impact of MASLD, a patient-centered approach is essential for effective treatment and improved long-term results. In this article, we provide an overview of key extrahepatic conditions commonly associated with MASLD and their clinical significance.

Objectives: Lung cancer is one of the most common malignancies worldwide. We aim to investigate the most effective treatments for advanced/nonadvanced stages of lung cancer patients.

Materials and methods: We searched electronic databases to investigate the treatment efficacies of lung cancer. The network meta-analysis was used to identify the top five most effective therapeutic strategies. A total of 157 studies were collected with a cumulative total of 164,678 participants.

Results: The results showed that the best top five treatments: (1) for advanced lung cancer in response rate, were Chemo + Chemotherapy + Targeted Therapy, Cell therapy + Immunotherapy, Targeted Therapy + Radiotherapy, Chemoradiotherapy + Immunotherapy, and Chemotherapy + Chemoradiotherapy with cumulative probabilities 50.5, 49.6, 47.7, 46.0, and 45.6%; (2) for advanced lung cancer in progression-free survival (PFS) rate, were Targeted + Radiotherapy, Targeted + Others Therapy, Targeted + Targeted Therapy, Immu + Immu + Chemo Therapy, and Chemoradiotherapy with cumulative probabilities 99.5, 82.8, 44.9, 36.5, and 33.6%; (3) for nonadvanced lung cancer in response rate, were Chemoradiotherapy + Immu, Chemoradiotherapy + Targeted therapy, Chemoradiotherapy + Others, Chemotherapy + Surgery, and Radiotherapy + Others with cumulative probabilities 79.1, 74.9, 66.9, 60.4, and 54.2%; (4) for non-advanced lung cancer in PFS rate, were Chemo + Surgery, Chemoradiotherapy + Targeted, Surgery, Surgery + Radiotherapy, and Chemoradiotherapy + Others with cumulative probabilities 88.3, 86.1, 78.3, 73.1, and 50.8%.

Conclusion: We present the latest and most effective therapeutic strategies for patients with advanced or nonadvanced stages of lung cancer.

This review focuses on the multifaceted roles of exosomal noncoding RNAs (ncRNAs) in colorectal cancer (CRC), utilizing the provided document as the primary source of information. Exosomes, nanoscale vesicles ranging from 30 to 150 nm, act as crucial mediators of intercellular communication, encapsulating bioactive molecules such as microRNAs (miRNAs) and long ncRNAs (lncRNAs). The biogenesis of exosomes involves the endocytic pathway, including the formation of multivesicular bodies and subsequent release of intraluminal vesicles into the extracellular space. This process is regulated by the endosomal sorting complex required for transport (ESCRT) machinery and other ESCRT-independent mechanisms, as well as RNA-binding proteins (RBPs) that selectively package ncRNAs. MiRNAs, shorter single-stranded RNA molecules, regulate gene expression post-transcriptionally by binding to target mRNAs, leading to translational repression or mRNA degradation. LncRNAs, longer RNA molecules, are involved in chromatin remodeling and transcriptional regulation and act as competing endogenous RNAs that modulate miRNA availability. Exosomal ncRNAs play a crucial role in tumorigenesis, where certain miRNAs promote proliferation while others act as tumor suppressors. Furthermore, these ncRNAs are central to the epithelial-mesenchymal transition, a critical process that facilitates metastasis. They also play a role in chemoresistance by modulating drug metabolism and apoptotic pathways. Exosomal ncRNAs also show promise as diagnostic and prognostic biomarkers due to their presence in body fluids and their association with disease progression. Moreover, they hold potential as therapeutic agents through RNA-based therapeutics and exosome-based drug delivery. The challenges involve standardizing exosome research, elucidating the underlying mechanisms, and ensuring successful clinical translation.