International Journal of Medical Sciences最新文献

Taekwondo is a combat sport that requires a specific skillset and high physical fitness. In 2022, the rules of taekwondo competitions rules were revised to increase match intensity. In this study, we developed and validated a high-intensity interval training (HIIT) protocol for taekwondo athletes and compared the outcomes of this protocol with those of regular training (control). A total of 12 athletes were randomly assigned to either an HIIT group or a control group. Body mass index, heart rate (HR), lactic acid level, and creatine kinase level were measured both before and after relevant intervention. Our HIIT protocol consisted of two phases. The first phase (weeks 1 and 2) involved six rounds of four kicking techniques (roundhouse, back, axe, and spinning kicks), each performed for 21 s with 12-s rest (work [exercise]-to-rest ratio: 1.75:1). The second phase (weeks 3 and 4) involved eight rounds of the same kicking techniques, each performed for 24 s with 8-s rest (work-to-rest ratio: 3:1). The participants rested for 1 min between two rounds. The kicks were performed at 85% and 90% of the maximum HR. Significant (p ≤ 0.05) between-group differences were observed in HR at work, HR at rest, lactic acid level, and creatine kinase level. Overall, this study indicates that implementing a sport-specific HIIT protocol can enhance the recovery of HR and lactic acid and creatine kinase levels in taekwondo athletes.

Background: Colorectal cancer remains a major contributor to global cancer-related mortality. Although EGFR-targeted monoclonal antibodies (cetuximab, panitumumab) have demonstrated efficacy in improving clinical outcomes, their associated adverse events underscore the need for enhanced prevention and management strategies. This study analyses real-world post-marketing data to enhance patient safety. Methods: The FDA Adverse Event Reporting System database served as the data source for this study, which centered on AEs related to cetuximab and panitumumab from 2004 to 2024. Standardized MedDRA queries are performed to fully search for AEs at the preferred term (PT) level. The analysis applied the reporting odds ratio (ROR) to identify AEs signals. The reliability of the findings was reinforced by employing multivariate logistic regression to handle confounders. Results: The analysis included 19,131 cetuximab primary suspect cases with 50,338 adverse events (AEs) and 9,448 panitumumab primary suspect cases with 30,061 AEs. The incidence of AEs for cetuximab in 24 organ systems and for panitumumab in 23 organ systems. Cetuximab had higher AE frequency in skin, vascular, and respiratory disorders, with the majority of skin-related AEs occurring within 15 days. Panitumumab showed stronger links to hypomagnesemia and hepatobiliary disorders, and and neurotoxicity, with skin AEs appearing around 28 days. Notably, panitumumab exhibited a higher risk of AEs compared to cetuximab and revealed a novel signal for hepatobiliary disorders. Conclusion: The study demonstrates substantial variations in the safety of cetuximab and panitumumab, emphasizing the need for tailored monitoring, prudent interchangeability, and management strategies in clinical practice. Future research should explore the underlying mechanisms and targeted interventions to improve patients' outcomes and quality of life.

Glioblastoma multiforme (GBM) is characterized by rapid progression, therapeutic resistance, and a profoundly immunosuppressive tumor microenvironment. Emerging evidence suggests that endoplasmic reticulum (ER)-associated macromolecules play critical roles in tumor adaptation. In this study, we performed a multi-omics investigation of orosomucoid-like protein 2 (ORMDL2), a conserved ER membrane protein involved in sphingolipid biosynthesis and ER stress regulation, and uncovered its regulatory functions in GBM progression. Transcriptomic analyses across The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) revealed elevated ORMDL2 expression in GBM tissues which causes poor prognosis. The MetaCore pathway and Gene Set Enrichment Analysis (GSEA) identified ORMDL2's involvement in antigen presentation via a major histocompatibility complex I (MHC class I), unfolded protein response (UPR), and mitochondrial apoptotic signaling. Single-cell RNA-sequencing data and the Human Protein Atlas showed ORMDL2 enrichment in tumor stromal cells. Pharmacogenomic correlation via the Genomics in Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) database suggested that ORMDL2 expression was associated with resistance to DNA damage response inhibitors such as etoposide, doxorubicin, talazoparib, and might interact with sphingolipid-targeting compounds. Collectively, our findings establish ORMDL2 as a multi-functional macromolecular regulator of immune suppression and therapeutic resistance in GBM, providing new mechanistic insights and potential targets for translational medicines.

Background: The differential diagnosis of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) presents significant challenges in clinical practice, as current diagnostic methods, such as renal biopsy, are invasive and lack specificity. This study aims to develop a non-invasive predictive model based on clinical and biochemical indicators to enhance diagnostic accuracy in distinguishing DKD from NDKD. The model is designed to serve as a decision-support tool for clinicians, improving renal health management in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective examination of data was executed. Clinical characteristics and laboratory data of T2DM patients who underwent renal biopsy at The First Affiliated Hospital of Sun Yat-sen University, spanning January 2015 to September 2023, were collated and stratified into a training cohort (January 2020 to September 2023) and an internal validation cohort (January 2015 to December 2019). A distinct analysis was conducted for patients with renal transplants within the validation cohort. Partial case data from Shenzhen Third Hospital (January 2022 to July 2025) and Southern Hospital (January 2018 to December 2023) were used as external validation cohort. The training cohort data underwent both univariate and multivariate regression analyses to formulate a predictive probability model, which was subsequently subjected to validation against the validation cohort. The efficacy of the model was meticulously assessed through metrics such as the area under the ROC curve, calibration plots, DAC, and the Hosmer-Lemeshow goodness-of-fit test. Results: The study encompassed a total of 1091 T2DM patients, including 385 with DKD, 585 with NDKD, and 121 with a concomitant diagnosis of DKD and NDKD, denoted as MIX. Membranous nephropathy was identified as the predominant pathological entity in both NDKD and MIX cases. The probability model incorporated six variables: gender, age, diabetes duration, diabetic retinopathy status, serum uric acid, and low-density lipoprotein levels. The model demonstrated robust discrimination and calibration capabilities for patients without renal transplants but exhibited diminished applicability for those with renal transplants. Conclusion: The research successfully established a model capable of accurately forecasting the likelihood of NDKD in the renal biopsy findings of T2DM patients. However, the model's applicability to patients with renal transplants is constrained, suggesting that future research endeavors should focus on enhancing the model to encompass a more diverse patient demographic.

The global incidence of prediabetes is on the rise, with an estimated 5 to 10% of individuals expected to transition to diabetes. We investigated factors associated with the progression of prediabetes to diabetes. Our primary data source was the Taiwan Biobank (TWB). The main outcome was the development of diabetes during the follow-up period among individuals who were initially diagnosed with prediabetes. We included 4,958 participants from the TWB, who were divided into four groups based on their levels of exercise. The exercise status of participants was assessed based on questionnaire responses collected during the enrollment and follow-up phases. Participants were categorized into one of the following groups: no exercise, transition from no exercise to exercise, transition from exercise to no exercise, and regular exercise. We used multiple logistic regression to establish the analysis model, which comprised 2,891 women and 2,067 men. The exercise group, comprising individuals who consistently engaged in exercise both at enrollment and during the follow-up period, exhibited a lower risk of developing diabetes (odds ratio [OR] = 0.755; 95% confidence interval [CI] = 0.640-0.892) compared to the no exercise group. When stratified by gender, the exercise group remained significantly associated with a reduced risk of diabetes in both women (OR = 0.752, 95% CI = 0.602-0.940) and men (OR = 0.762, 95% CI = 0.591-0.982). This study provides evidence of a significant association between maintaining regular exercise habits and a lower risk of diabetes among Taiwanese adults with prediabetes.

Introduction: Chromatin assembly factor 1B (CHAF1B), a pivotal regulator of chromatin assembly following DNA replication, has been implicated in oncogenic processes. However, its role in sorafenib resistance and potential anti-tumor mechanisms in hepatocellular carcinoma (HCC) remain unclear. This study has sought to elucidate CHAF1B's therapeutic potential and its potential synergistic role with sorafenib in overcoming chemoresistance. Methods: In this study, bioinformatics, immunohistochemistry, western blot, CCK8, colony formation, transwell migration and invasion, and flow cytometry were performed to analyze the correlation between CHAF1B and sorafenib resistance in HCC. Furthermore, RNA sequencing (RNA-seq), combined with signaling pathway-specific inhibitors, was used to elucidate the specific role of CHAF1B in sorafenib resistance of HCC and its related mechanism. Results: CHAF1B was significantly upregulated in HCC tissues and sorafenib-resistant HCC cells, with elevated expression correlated with reduced survival probability in HCC patients. Moreover, high CHAF1B levels predicted poorer clinical outcomes in sorafenib-treated patients. Functional assays revealed that CHAF1B promotes HCC cell proliferation, migration, and invasion, while also enhancing resistance to sorafenib. In contrast, knockdown of CHAF1B significantly increased sorafenib-induced inhibition of proliferation and cell death. Mechanistically, CHAF1B facilitated malignant phenotypes via activation of the PI3K/Akt/HIF-1α pathway. Furthermore, blockade of PI3K/Akt/HIF-1α signaling partially attenuated the CHAF1B-mediated sorafenib resistance. Conclusion: CHAF1B is a key regulator of sorafenib resistance, and targeting CHAF1B in conjunction with sorafenib may represent a promising therapeutic approach for HCC by modulating the PI3K/Akt/HIF-1α signaling axis.

Tetrahydrocurcumin (THC), a major curcuminoid metabolite known for its antioxidant and anti-inflammatory properties, has potential for reducing brain inflammation. This study investigated THC's anti-inflammatory responses and molecular mechanisms against Pseudomonas aeruginosa LPS (P.a. LPS)-induced NLRP3 inflammasome and ROS-producing cell pyroptosis. In the current study, we showed that THC significantly attenuated P.a. LPS-induced inflammasome factor IL-18 production through lysosomal dysfunction and leakage of cathepsin B. Importantly, THC reduced the levels of NLRP3 inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, ASC, N-GSDMD, and IL-18. We also demonstrate that the inhibition of NLRP3 inflammasome activation by THC is ROS-dependent, via inhibition of H₂O₂ production, SOD activity, and enhancement of GSH activity. Subsequently, we demonstrated that THC treatment significantly reduced LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and increased heme oxygenase-1 (HO-1) expression in BV-2 cells. Furthermore, we used MAPKs (SB203580, SP600125, and U0126) and HO-1 (SnPP) inhibitors to demonstrate that THC modulated inflammasome-mediated pyroptosis may be related to p38 and JNK MAPK and HO-1-dependent inflammatory signaling. Overall, THC can inhibit ROS-triggered NLRP3 inflammasome-mediated pyroptosis by promoting GSH activity and HO-1 expression via modulating the p38 and JNK signaling pathways in P.a. LPS-treated BV-2 cells.

Sensorineural hearing loss (SNHL)'s incidence is on the rise, severely affecting the quality of life of patients and even causing psychological and mental damage. It also poses a heavy burden on the global healthcare system. The auditory process involves the conversion of mechanical signals generated by the vibration of the basilar membrane into electrical signals by sensory hair cells. These signals are then transmitted to the spiral ganglion neurons, which receive input from inner hair cells and relay the information to the cochlear nucleus in the brainstem, and subsequently to the auditory cortex. Calcium plays a crucial role in this process, influencing homeostasis of the cochlear environment, the mechanoelectrical transduction channels and synaptic neurotransmitter release. Due to the increasing risks associated with aging, noise exposure, ototoxic drugs, and genetic mutations, the incidence of SNHL is continuously rising. Notably, SNHL often manifests as a disruption of calcium homeostasis. Therefore, it is essential to understand the potential mechanisms of calcium signaling in SNHL, providing new insights into the pathogenesis and treatment of SNHL. This review focuses on the mechanisms of calcium signaling in SNHL, including factors affecting calcium homeostasis and potential therapeutic approaches.

Ziyun Ointment, a traditional Chinese herbal remedy, is often applied externally; however, its physiological effects on the skin have not been thoroughly studied. This study aimed to assess the skin parameters of psoriasis patients before and after 12 weeks of Ziyun Ointment application.

Methods: 30 participants were recruited and classified into mild, moderate, and severe. The pre-test and post-test measurements of skin parameters, including melanin and erythema index, stratum corneum lipids, stratum corneum hydration, and transepidermal water loss (TEWL), were conducted using the non-invasive Cutometer Dual MPA580.

Result: 80% of the patients improved PASI, and the PASI score was significantly reduced by 2.58 ± 1.35 (p < 0.05). After continuous use of Ziyun Ointment for 49 days, the psoriasis area of all subjects was significantly reduced by 42% ± 4%, especially in the erythema index (p = 0.028). Ziyun Ointment significantly reduced the degree of skin transepidermal water loss by 26% (p = 0.04).

Conclusion: Ziyun Ointment retains the hydration in the skin and reduces the loss of moisture from the skin. We also suggest that Ziyun Ointment be used for at least 12 weeks to observe significant improvements. Ziyun Ointment has a physiological significance in maintaining skin moisture.

Non-small cell lung cancer (NSCLC), as one of the most commonly diagnosed cancers globally, requires expedited identification of new drug targets. We conducted proteome-wide MR using genetic data for 4,853 plasma proteins. Summary-level data on lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) were extracted from GWAS meta-analyses (11,273 and 7,426 cases, respectively) and FinnGen cohort (1,590 and 1,510 cases, respectively). We genetically identified eight proteins with a causal role in the etiology of NSCLC. Lower levels of five proteins (CDH17, CXADR, FAM3D, POGLUT3, SFTPB) and higher levels of two proteins (CEACAM5, KLK1) were linked to increased LUAD risk, while higher CD14 levels were associated with elevated LUSC risk. Two proteins, POGLUT3 and SFTPB were validated through Bayesian colocalization. One protein SFTPB was identified using SMR and HEIDI tests. Bidirectional MR found no reverse causality. The primary findings were validated through scRNA-seq, GeneMANIA, GO analysis, druggability assessments and PheWAS analysis. These protein-coding genes are primarily expressed in epithelial cells, macrophages, monocytes, and endothelial cells. Furthermore, CEACAM5, KLK1, and CD14 correspond to existing drugs. These proteins may deepen our comprehension of the etiology and could serve as appealing novel biomarkers and drug targets for NSCLC management.