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Ayer — Junio 17th 2026PLOS ONE Medicine&Health

Screening disease feature genes and analyzing correlations with immune cell infiltration in knee osteoarthritis chondrocytes based on multiple machine learning algorithms

by Jing-le Zhuge, Xi-yong Li, Yong-le Wang, Juan-fen Ma

Objective

This study aimed to comprehensively analyze differentially expressed genes (DEGs) in chondrocytes from patients with knee osteoarthritis (OA) by integrating multiple machine learning algorithms and bioinformatics techniques, to unravel the underlying molecular mechanisms associated with OA chondrocytes, and to provide novel insights for the innovation of clinical therapeutic strategies.

Methods

We downloaded the GSE117999, GSE114007, GSE169077, GSE246425, and GSE178557 datasets from the public Gene Expression Omnibus (GEO) database as the training set, while GSE57218 served as an independent validation set. To ensure data consistency and comparability, the training set was normalized, and the ComBat algorithm was applied to eliminate batch effects, yielding a merged gene expression dataset. Subsequent differential expression analysis was performed to identify genes with significant changes under disease conditions, followed by enrichment analysis. To more accurately identify genes closely linked to disease characteristics, we independently analyzed the merged dataset using three machine learning algorithms: Lasso regression, random forest, and support vector machine (SVM). The intersection of results from these three methods was used to construct a robust list of disease-related feature genes. These prominent feature genes were validated in the training set and further externally confirmed using the GSE57218 dataset. Additionally, the CIBERSORT algorithm was employed to quantify immune cell infiltration in the normalized gene expression data, selecting infiltration results with high reliability (P  Results

DDIT3 and PFKFB3 were significantly downregulated in OA patients. DDIT3 was specifically associated with lipid metabolism, apoptosis, and inflammatory genes (e.g., TNFRSF12A), whereas PFKFB3 was linked to phospholipid synthesis and cell cycle genes (e.g., CHKA). Both genes were associated with core OA-related pathways, including PI3K-Akt and AGE-RAGE. Immune infiltration analysis revealed that DDIT3 was positively correlated with pro-inflammatory mast cells and M1 macrophages, while PFKFB3 was negatively correlated with activated dendritic cells. Collectively, these two genes were associated with immune cell infiltration patterns. The competing endogenous RNA (ceRNA) network analysis indicated that DDIT3 was associated with axes such as LINC00689-miR-769-5p, and PFKFB3 was associated with complex networks like GAS6-AS1-miR-146a-5p.

Conclusion

DDIT3 and PFKFB3 are key candidate genes associated with the pathological progression of OA. Their downregulation is correlated with inflammatory and metabolic disturbances in chondrocytes, supporting their potential use as diagnostic biomarkers and therapeutic targets for OA.

AnteayerPLOS ONE Medicine&Health

Immunomodulatory effects of a multi-component pharmacological intervention on diabetic peripheral neuropathy in type 2 diabetic rats: An exploratory study

by Lu Zhang, Si Wang, Jie Lei, Lingrui Zeng, Ailin Lu, Yongqing Wu, Yuan Shi, Jing Yang, Mengrui Yuan, Hongyi Liu

Background

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) and is closely linked to immune and inflammatory dysregulation. Multi-component pharmacological interventions have been explored as complementary approaches for metabolic and immune modulation; however, their effects on DPN and related mechanisms remain incompletely understood.

Methods

A rat model of T2DM-associated peripheral neuropathy was established, and a multi-component pharmacological intervention (MPCI) was administered for 8 weeks. Peripheral nerve dysfunction was evaluated by motor and sensory nerve conduction velocities (MNCV and SNCV), behavioral outcomes, and histological/ultrastructural assessments. In parallel, spleen tissues were collected for transcriptomic profiling. RNA sequencing was performed to identify differentially expressed genes and immune-related pathways, and representative molecules involved in inflammatory regulation were further validated using western blotting and quantitative real-time PCR in sciatic nerve tissue.

Results

MPCI administration significantly ameliorated peripheral nerve dysfunction in T2DM rats, as evidenced by improved nerve conduction velocities and pathological features. Transcriptomic analysis of spleen tissue revealed that MPCI was associated with broad remodeling of diabetes-related immune and inflammatory gene programs. In parallel, sciatic nerve analyses showed attenuation of NF-κB/c-Jun–associated inflammatory signaling and modulation of inhibitory regulators at both the protein and mRNA levels.

Conclusion

These findings indicate that MPCI improves T2DM-associated DPN and is associated with splenic immune remodeling and attenuation of peripheral nerve inflammatory signaling, providing exploratory evidence for associations between splenic immune transcriptomic remodeling and peripheral nerve inflammatory signaling.

Identification and functional analysis of key miRNAs and target genes associated with failure of HBV mother-to-child transmission prevention

by Quan He, Xiong Zou, Chunyan Zheng, Jiawei Zhang, Jialing Li, Liping Hu, Ting Zeng, Zijuan Huang, Peipei Zeng, Jinli Wei, Haichen Cui, Yongjian Su, Hai Li

Background

Residual mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant clinical challenge despite standard immunoprophylaxis. Identifying molecular markers is crucial for improved prevention and diagnosis.

Methods

We conducted a case-control study using the Guangxi Liuzhou HBV MTCT registry. Peripheral blood RNA sequencing (Illumina HiSeq) was performed on infants from HBsAg-positive mothers: cases (HBsAg-positive, n = 6) and controls (HBsAg-negative, n = 10). All infants receive HBIG and the first dose of hepatitis B vaccine within 24 hours after birth, followed by completion of the three-dose vaccination series. Differentially expressed miRNAs (DEMs; adj-p  1) were identified. Target genes were predicted (miRanda/RNAhybrid) and functionally analyzed (GO/KEGG enrichment, PPI network). HBV-associated target genes were identified by cross-referencing GeneCards/NCBI.

Results

RNA-seq identified 62 DEMs (19 upregulated, 43 downregulated). Target prediction yielded 5,014 genes. Functional enrichment highlighted key pathways and processes. PPI analysis pinpointed highly connected genes. Integration with HBV databases revealed 3 key target genes potentially modulated by 4 specific DEMs (hsa-miR-6747-3p, hsa-miR-4772-3p upregulated; hsa-miR-4676-5p, hsa-miR-485-5p downregulated).

Conclusion

This study identifies dysregulation of 4 key miRNAs and their association with 3 HBV-linked target genes as potential contributors to residual HBV MTCT. These findings provide novel insights into the molecular mechanisms underlying HBV MTCT and suggest potential targets for intervention.

Short-duration phase-change material cryotherapy selectively enhances early neuromuscular and perceptual recovery

by Chong Gang, Hao Wang, Yujue Wang, Yongsheng Lan

The purpose of this study was to examine whether short-duration phase-change material cooling (PCM) applied at different temperatures influences acute recovery following fatigue induced by stretch–shortening cycle exercise (SSC). Sixty-four physically active participants were randomly assigned to 5°C, 10°C, or 15°C PCM cryotherapy group or a passive recovery control group. After completing a SSC fatigue protocol, participants underwent a 15-minute PCM intervention, and peak torque (PT), mean power, rate of force development (RFD), countermovement jump (CMJ) performance, Rating of perceived exertion (RPE), modified endurance ratio (MER), vastus lateralis (VL) and Rectus Femoris (RF) stiffness were assessed immediately after fatigue (Imm-fatigue), immediately after PCM cryotherapy (Imm-PCM), and 60 minutes post PCM cryotherapy (Post60-PCM). Mean power and RFD were significantly greater in PCM groups compared with the control group at Imm-PCM (P ≤ 0.01), with mean power remaining elevated in the 15°C PCM group at post-60-PCM (P ≤ 0.05). RPE was significantly lower in all PCM groups at Imm-PCM and post60-PCM compared with control (P ≤ 0.01). No between-group differences were observed for PT, CMJ, MER, or muscle stiffness, and no temperature-dependent effects were detected within the 5–15 °C. These findings indicate that 15-minute PCM cryotherapy selectively accelerates early-phase neuromuscular and perceptual recovery without affecting maximal strength, endurance capacity, or passive muscle mechanical properties. From an applied perspective, PCM cryotherapy may be an effective strategy to enhance explosive performance and perceived readiness during short recovery intervals in training or competition settings.

Perspectives on multimorbidity care provision among public hospital-based healthcare workers in Blantyre and Chiradzulu, Malawi: A qualitative study

by Gift Treighcy Banda-Mtaula, Ibrahim Simiyu, Sangwani Nkhana Salimu, Stephen A. Spencer, Nateiya M. Yongolo, Marlen Chawani, Hendry Sawe, Jamie Rylance, Ben Morton, Adamson S. Muula, Eve Worall, Felix Limbani, Miriam Taegtmeyer, Rhona Mijumbi, on behalf of the Multilink consortium

Multimorbidity, the presence of multiple chronic health conditions, is a leading cause of death globally. In Malawi, chronic noncommunicable and communicable diseases such as HIV frequently co-exist, putting pressure on an under-resourced system. However, the health system is primarily structured around disease-specific [vertical] programs, which hinders person-centred care approaches to multimorbidity. Our study focuses on multimorbidity care and explores the perceptions of healthcare workers on the patient pathways and service organisation throughout the patient’s interaction with the health facilities. This cross-sectional qualitative study took an interpretivist approach. We conducted 13 days of clinical observations at Queen Elizabeth Central Hospital and Chiradzulu District Hospital. We also conducted 13 days of clinical observations and semi-structured in-depth interviews with different cadres of purposively sampled healthcare workers (n = 22) at Queen Elizabeth Central Hospital and Chiradzulu District Hospital. Through thematic analysis, we identified an understanding of the organisation of care and healthcare workers’ perspectives on the delivery of services. Findings showed both hospitals provided services for inpatients and outpatients with multimorbidity, including screening, management, prevention of secondary conditions and rehabilitation. Patient diagnosis and management for multimorbidity were often delayed due to frequent stockouts of medication and consumables necessary for diagnostic testing for NCDs at the hospital level. Some healthcare workers were not equipped with the knowledge, skills, or guidelines to manage multimorbidity. As HIV care is currently better resourced than other chronic conditions, healthcare facilities may strengthen the supply chain, healthcare workers’ training sessions and monitoring and evaluation tools to ensure NCDs are well managed, learning from HIV programmes.

Associations of tumor necrosis factor alpha genetic variants with metabolic syndrome and type 2 diabetes mellitus in a Thai population

by Metha Yaikwawong, Khanittha Kamdee, Kasarnchon Mek-yong, Somlak Chuengsamarn

This work aimed to clarify how polymorphisms in the TNF gene relate to metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and a broad spectrum of cardiometabolic characteristics, while also determining their impact on circulating TNF‑α concentrations. A total of 765 participants were genotyped for rs1800629 and rs361525, and serum TNF-α was also measured. To assess these relationships, multivariable logistic regression models—incorporating age, sex, and body mass index (BMI)—were applied to estimate adjusted odds ratios (aORs) and their corresponding 95% confidence intervals (CIs). Both variants were significantly associated with MetS: rs1800629 (crude OR = 2.22, 95% CI: 1.45–3.44, P P P = 0.035; adjusted OR = 2.84, 95% CI: 1.17–7.31, P = 0.025). The rs1800629 variant was also linked to T2DM risk (adjusted OR = 2.61, 95% CI: 1.35–5.24, P = 0.006), whereas rs361525 showed no such association. Carriers of rs1800629 had higher mean TNF-α levels (P

Research on epilepsy detection methods based on interpretable features and machine learning

by Yongxin Sun, Xiaojuan Chen, Xinghua Zhang, Xiaohui Cai

Epilepsy is a prevalent neurological condition that impacts a significant number of individuals worldwide. Patients’ physical and mental health, as well as their daily activities, are significantly affected by seizures, necessitating prompt diagnosis and treatment. The automatic detection of epilepsy using electroencephalogram (EEG) signals has been a significant area of research. Nevertheless, the majority of current methods are based on intricate feature engineering processes that require the extraction and selection of a large number of features to identify the most discriminative feature sets. This results in a high level of algorithmic complexity, inadequate robustness, and inadequate interpretability, which complicates the provision of theoretical support to clinicians. This paper proposes a pathophysiology-driven, interpretable machine learning algorithm to address the limitations of current EEG-based epilepsy detection methods, which include poor interpretability and complex feature engineering. We developed a low-dimensional, interpretable feature combination consisting of only five features and systematically validated its discriminative capability across various epilepsy phases by innovatively integrating electrophysiological markers of epileptic seizures with nonlinear dynamical properties. In the binary classification of seizure versus non-seizure EEG segments, the XGB classifier achieved the highest accuracy of 98.73% and an F1 score of 98.57%. Classification accuracy for interictal versus ictal periods reached 95.33%, with an F1 score of 95.27%. In the challenging ternary classification task encompassing preictal, interictal, and ictal periods, the model achieved a respectable accuracy of 86.3% and an F1 score of 85.79%. Cross-database validation yielded a maximum accuracy of 82.17% and an F1 score of 81.99%, confirming the proposed features’ robust generalization capability and transformative potential. This feature set exhibits outstanding and stable performance across all models, as demonstrated by evaluations across two public datasets using five machine learning classifiers. In addition, SHAP values quantified the contribution of each feature to predictions, thereby providing a transparent decision-making rationale that substantially improves the algorithm’s interpretability and clinical utility.

Design and implementation of a comprehensive management platform for drilling engineering

by Yaosen Du, Yiyong Yang, Xiaolong Wu, Pengju Gao, Hanchen Ma

To enhance the efficiency, safety, and data accuracy of drilling engineering, this study developed an integrated business management platform for drilling engineering grassroots units based on the Business Model Driven (BMD) approach. The platform is built on a “five horizontal, three vertical” cloud computing architecture, establishing a five-layer system from the infrastructure layer to the user layer horizontally, and supported by standard specifications, safety, and maintenance systems vertically, enabling collaboration across multiple business scenarios and data integration. Currently, four major modules with over 20 functionalities have been developed, supporting applications such as task coordination, engineering supervision, data analysis, and accident handling. Operational results demonstrate that the platform effectively promotes integrated management of drilling engineering through real-time data sharing, full-process quality control, and intelligent decision-making, thereby enhancing operational quality and safety, reducing accident risks, and providing critical technological support for the digital transformation and upgrading of the drilling industry.

A non-invasive urinary diagnostic signature for diabetic kidney disease revealed by machine learning and single-cell analysis

by Yonggang Chen, Jintai Luo, Yingying Zheng, Xiaomei Jiang, Zixiang Yang, Xiaobing Liu

Background

Diabetic kidney disease (DKD) poses a significant health burden with inadequate diagnostic sensitivity. This study develops non-invasive biomarkers by integrating urinary and renal single-cell sequencing with machine learning.

Methods

This study analyzed DKD single-cell and bulk transcriptomic data from public repositories. We established a computational pipeline to distinguish kidney-originating cells in urinary sediments, enabling the identification of injury-associated gene signatures. These signatures were refined using machine learning to develop a diagnostic model, which was validated in independent cohorts. The biomarkers were further verified in DKD renal tissues at single-cell resolution and across multiple nephropathies. Functional and spatial analyses confirmed biological relevance using transcriptomic and histological validation.

Results

Single-cell analysis of 2,089 urine-derived cells identified eight renal cell types, including injured proximal tubule cells (Inj-PTC) showing upregulated injury markers (HAVCR1, VCAM1) and enriched apoptotic/TGF-β pathways. A machine learning-selected biomarker panel (PDK4, RHCG, FBP1) demonstrated strong diagnostic value (area under the curve, AUC > 0.9), with consistent downregulation across multiple chronic kidney diseases. PDK4 and FBP1 were specifically suppressed in DKD renal Inj-PTC (p  Conclusions

This study identifies a three-gene biomarker panel (PDK4, RHCG, FBP1) as a promising non-invasive diagnostic tool for DKD. While demonstrating excellent diagnostic performance. It represents a tubular injury-associated gene signature that is detectable in urinary cells and shows strong association with DKD in transcriptomic datasets, presenting a promising candidate for a non-invasive diagnostic assay.

Far-infrared irradiation attenuates vessel contraction by activating SERCA2 through disruption of SERCA2 and PLN interaction

by Yun-Jin Hwang, So-Young Park, Jung-Hyun Park, Du-Hyong Cho

Vascular smooth muscle cells (VSMCs) plays an important role in maintaining vascular function by responding to various vasoactive stimuli within blood vessels. Far-infrared (FIR) rays has been shown to possess a variety of physiological effects including vasodilation, while the underlying molecular mechanism remains elusive. Here, we explored the molecular mechanism by which FIR irradiation suppresses vascular contraction using rat VSMCs and aortas. FIR irradiation enhanced the transport of intracellular Ca2+ from the cytosol to the sarcoendoplasmic reticulum (SER) via activation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA), which accompanied a decrease in intracellular ATP levels. Pretreatment with thapsigargin (TG), a specific SERCA inhibitor, or knockdown of SERCA2 gene expression reversed FIR irradiation-induced translocation of Ca2+ into the SER. Notably, FIR irradiation promoted the dissociation of SERCA2 and phospholamban (PLN), an endogenous SERCA inhibitor, without altering their total protein expression levels. The array of effects elicited by FIR irradiation was not observed under hyperthermic conditions (39°C). Moreover, FIR irradiation, but not hyperthermal condition, decreased the phosphorylation of myosin light chain (MLC) at Ser19, which was restored by pretreatment with TG or the knockdown of SERCA2 gene expression. FIR irradiation attenuated phenylephrine-induced vessel contraction in endothelium-deprived rat aortas. Consistent with the in vitro results, the reduction in MLC phosphorylation caused by FIR irradiation was reversed following pretreatment with TG in isolated aortas. Additionally, FIR irradiation increased blood flow in the carotid arteries of mice. Collectively, these results suggest that FIR irradiation activates SERCA2 by promoting its dissociation from PLN, independent of hyperthermic effects. This activation lowers cytosolic Ca²⁺ and ATP levels, reducing MLC phosphorylation and vascular smooth muscle contraction. These findings provide scientific evidence for the therapeutic potential of FIR therapy in the treatment and prevention of arterial narrowing conditions such as pathological vasospasm, and peripheral artery disease.

Comparison of outcomes between minimally invasive percutaneous bunnell suture and traditional open modified Kessler technique for acute closed achilles tendon rupture: A single-center cohort study

by Zihang Zhao, Xiang Zhang, Xi Hou, Zihan Liu, Zhiyong Hou, Lianxin Song, Ruipeng Zhang

Percutaneous Bunnell repair and open modified Kessler repair remain debated options for acute Achilles tendon rupture (AATR). We retrospectively compared a minimally invasive percutaneous Bunnell technique (Group A) with an open modified Kessler repair (Group B) within a standardized early functional rehabilitation (EFR) protocol at a single center. Fifty-five adults with closed AATR treated between January 2021 and December 2022 were analyzed (Group A, n = 25; Group B, n = 30). Between-group comparisons used Welch t tests for continuous variables and χ² or Fisher exact tests for categorical variables; American Orthopaedic Foot & Ankle Society (AOFAS) and Achilles Tendon Total Rupture Score (ATRS) were assessed at 12 and 24 weeks, with Holm adjustment applied within each scale. Compared with Group B, Group A had shorter operative time (56.6 ± 15.1 vs 68.2 ± 23.2 minutes; mean difference −11.6; 95% CI −22.05 to −1.15; P = 0.030), less intraoperative blood loss (28.4 ± 8.4 vs 74.7 ± 19.4 mL; −46.3; 95% CI −54.22 to −38.38; P 

Impacts of polymorphisms in drug-metabolizing enzyme and transporter genes on irinotecan toxicity and efficacy in Thai colorectal cancer patients

by Natthakul Akarapredee, Chalirmporn Atasilp, Chonlaphat Sukasem, Pimonpan Jinda, Rattanaporn Sukprasong, Jiraporn Jensuriyarkun, Soravit Wongjitjanyong, Patompong Satapornpong, Natchaya Vanwong

Introduction

Irinotecan is a chemotherapy agent commonly prescribed for metastatic colorectal cancer but often leads to neutropenia. Variations in genes encoding drug-metabolizing enzymes and transporters may affect the toxicity and effectiveness of irinotecan. This study aimed to examine the impact of these genetic polymorphisms on irinotecan outcomes in Thai colorectal cancer patients.

Methods

The study retrospectively analyzed 41 metastatic colorectal cancer patients treated with irinotecan-based chemotherapy. Genotyping was conducted for 23 single nucleotide polymorphisms in genes including UGT1A1, CYP3A4, CYP3A5, CES1, ABCB1, ABCC2, ABCC5, ABCG1, ABCG2, and SLCO1B1.Toxicity and efficacy were assessed, with statistical significance set at a Bonferroni-corrected P value  Results

In terms of toxicity, UGT1A1*6 was significantly associated with both all-grade and severe neutropenia in the first cycle (p p p ABCC2 -24C > T variant was linked to all-grade neutropenia in the second cycle (p = 0.001). For efficacy, patients with the wild-type UGT1A1*6 had longer progression-free survival (PFS) (p SLCO1B1 521T > C variant was associated with improved PFS (p  Conclusion

UGT1A1*6 and ABCC2 -24C > T variants emerge as potential predictors of irinotecan-induced neutropenia, while UGT1A1*6 and SLCO1B1 521T > C may serve as markers of prolonged PFS in Thai patients. Validation through larger prospective studies is essential to confirm and refine these genetic associations.

Prediction of early recovery in patients with acute peripheral facial paralysis using serial electroneuronography

by Yong Seok Jo, Seung Jae Lee, Hyun Jin Lee, Jeon Mi Lee

Objectives

This study aimed to determine the preferred timing and measurement sites for electroneuronography (ENoG) to predict early recovery from acute peripheral facial paralysis.

Methods

We retrospectively evaluated 42 patients with acute peripheral facial paralysis who received standard treatment with oral corticosteroids. The severity of facial paralysis was assessed at the initial visit and after 1 month using the House–Brackmann grading system. Patients were classified into recovery and non-recovery groups according to changes in the grade. ENoG was performed at the initial visit and after 2 weeks. ENoG amplitudes of four facial muscles (frontalis, nasalis, orbicularis oculi, and orbicularis oris) at the initial visit and after 2 weeks, as well as age, sex, affected side, and diagnosis, were compared between the two groups.

Results

No differences were observed in degeneration ratios across all subsites in the initial ENoG, which can be explained by the fact that Wallerian degeneration is not yet complete at this early stage. However, the second ENoG, performed after degeneration had progressed, showed significant differences across all subsites. Binary logistic regression analysis revealed that the degeneration ratio of the orbicularis oris muscle was the best predictor of early recovery (odds ratio, 0.961; p = 0.014). Receiver operating characteristic curve analysis also revealed that the degeneration ratios of all subsites measured in the second ENoG were useful in predicting early recovery, with the highest possibility at the orbicularis oris muscle (area under the curve = 0.789). When the degeneration ratio exceeded 60% in all subsites in the second ENoG, a favorable prognosis was not expected.

Conclusion

This study provides the preferred testing time and measurement sites for ENoG to predict early recovery from facial paralysis. Given the personal and social impact of facial paralysis, predicting early recovery is crucial for reassuring patients, providing better treatment, and encouraging early reintegration into society.

MiR-125b-5p and miR-100-5p as Biomarkers and therapeutic targets for the prevention of particulate matter-induced non-smoker lung cancer

by Moe Thi Thi Han, Tay Zar Myo Oo, Busayamas Chewaskulyong, Sakorn Pornprasert, Kanyamas Choocheep, Khanittha Punturee, Warunee Kumsaiyai, Yupanun Wuttiin, Sawitree Chiampanichayakul, Ratchada Cressey

Non-smoking-related lung cancer is increasingly associated with environmental factors such as particulate matter (PM) exposure. Using deep small RNA sequencing, we identified distinct miRNA expression patterns in lung cancer patients compared to non-cancer controls, stratified by smoking status. Notably, hsa-miR-125b-5p and hsa-miR-100-5p were significantly downregulated in non-smoking lung cancer patients. Pathway enrichment analysis revealed smoking amplifies pathways related to glycan biosynthesis, signal transduction, and transcriptional regulation, while non-smoking lung cancer is characterized by immune dysfunction and metabolic alterations, including oxidative phosphorylation and natural killer cell cytotoxicity. Validation in a larger cohort using quantitative RT-PCR confirmed the suppression of miR-125b-5p and miR-100-5p in non-smoking lung cancer patients. Additionally, miR-203a and miR-199a-3p were identified as potential biomarkers for lung cancer, independent of smoking status. Chronic PM exposure in primary bronchial/tracheal epithelial cells initially elevated miR-125b-5p and miR-100-5p expression, but prolonged exposure suppressed these miRNAs while increasing their target genes, TXNRD1 and HOXA1, suggesting stress-induced dysregulation. Functional studies using miRNA mimics demonstrated that miR-125b-5p and miR-100-5p suppress PM-induced cancer cell mobility and colony formation, with miR-125b-5p exhibiting broader effects. These findings underscore the critical roles of miR-125b-5p and miR-100-5p in PM-associated lung cancer progression and their potential as biomarkers and therapeutic targets. This study highlights distinct mechanisms of lung carcinogenesis in smokers and non-smokers, providing a foundation for targeted interventions in PM-associated lung cancer.

Effect of fascial closure using barbed sutures on incisional hernias in midline laparotomy for gynecological diseases: A multicenter randomized controlled trial (KGOG 4001)

by Yong Jae Lee, Nam Kyeong Kim, Kidong Kim, Chel Hun Choi, Keun Ho Lee, Jong-Min Lee, Kwang Beom Lee, Dong Hoon Suh, Sunghoon Kim, Min Kyu Kim, Seok Ju Seong, Myong Cheol Lim

Objective

To identify the effect of fascial closure using barbed sutures on the incidence of incisional hernia in patients undergoing elective midline laparotomy for gynecological diseases.

Methods

In this multicenter, non-blind randomized controlled trial conducted from February to December 2021, patients with a BMI 2 and aged >18 years, scheduled for midline laparotomy, were randomly assigned to receive either barbed (experimental) or non-barbed sutures (control) for fascial closure. The primary outcome was the cumulative incidence rate of incisional hernia up to 1-year post-surgery. Secondary outcomes included incisional hernia up to 2-years post-surgery, wound complications, and postoperative pain assessed by Brief Pain Inventory-Korean scores, and Numeric Rating Scale.

Results

Out of 174 patients (experimental, 86; control, 88), 36 were excluded due to dropout or loss to follow-up, leaving 138 patients (experimental, 67; control, 71) included in the analysis. The groups were balanced in terms of cancer surgeries, mean wound length, and mean surgery time. The cumulative incidence rates of incisional hernia up to 1-year (0.0% vs. 1.4%; p > 0.999) and 2-years (0.0% vs. 3.4%, p = 0.496) post-surgery did not differ significantly between the experimental and control groups. Additionally, no significant differences were observed in the incidence of wound dehiscence 4 weeks post-surgery, cumulative incidences of wound dehiscence and wound infection up to 4 weeks post-surgery, or postoperative pain scores between the groups.

Conclusions

Fascial closure using barbed sutures resulted in no cases of incisional hernia up to 2-years post-surgery, but did not demonstrate a significant reduction in incisional hernia rates compared with the non-barbed suture.

Trial registration

ClinicalTrials.gov NCT04643197

Safety of penicillamine and trientine in the treatment of Wilson’s disease: An analysis of the FDA Adverse Event Reporting System (FAERS) database

by Wenlong Qian, Kou Xu, Shuo Li, Zhuo Zhang, Xiaoxiao Hou, Bingjie Min, Jia Ling, Xinyu Zhu, Hui Zhou, Wenjuan Xu, Wenming Yang, Shijian Cao, Yonghua Chen

Background

Penicillamine(D-Penicillamine) and trientine are first-line therapies for Wilson’s Disease (WD), yet real-world data on their adverse events (AEs) remain scarce. We analyzed the FDA Adverse Event Reporting System (FAERS) to comprehensively assess the safety of penicillamine and trientine in WD treatment.

Methods

AEs for penicillamine and trientine (2004Q1–2024Q4) were analyzed using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN).

Results

We found 1,452 and 760 AEs related to penicillamine and trientine, respectively. In all adverse event (AE) reports, the ratio of females to males was approximately 1.3, with the highest proportion of AE reports in the 21–30 age group, and the largest number of AE reports coming from the United States. Signal detection showed that the most commonly reported AEs for penicillamine and trientine were drug hypersensitivity and tremor, respectively, with the highest proportions in the SOC categories of immune system disorders and gastrointestinal disorders. The main AEs for both drugs involved condition aggravated, and identified potential safety signals requiring further validation for the two drugs, such as decreased bone density and brain atrophy for penicillamine, and memory impairment, oesophageal ulcer and starvation for trientine. In addition, we found that women were more likely to experience drug hypersensitivity in penicillamine adverse event reports, while men were more likely to experience cutis laxa.

Conclusion

This study reveals the characteristics of AEs and potential associated risks in the clinical application of penicillamine and trientine, emphasizing individualized medication and vigilant monitoring strategies to provide guidance for safe medication use.

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