PeerJ最新文献

Purpose: This retrospective analysis aimed to assess the therapeutic efficacy and adverse event profile of tislelizumab combined with lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), predominantly of hepatitis B virus (HBV) etiology. While this combination has shown promise in clinical trials, real-world data in HBV-endemic populations remain sparse.

Methods: A total of 163 uHCC patients who initiated first-line systemic therapy with tislelizumab and lenvatinib between January 2021 and February 2025 were retrospectively analyzed. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Key clinical endpoints included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), disease control rate (DCR), treatment-emergent adverse events (TRAEs), and other relevant outcomes. Prognostic factors were explored through subgroup analyses and multivariate Cox proportional hazards modeling.

Results: Of the 163 patients (84.7% HBV-related), the ORR was 25.8%, DCR was 67.5%, and median PFS was 13.87 months. Additionally, 16.6% of patients achieved conversion therapy and subsequent surgical resection. Subgroup and multivariate analyses indicated that a larger tumor burden, particularly tumors ≥5 cm, was associated with shorter PFS but did not significantly affect OS. TRAEs were observed in 86% of patients, with grade ≥3 events occurring in 5%.

Conclusions: This analysis supports that tislelizumab plus lenvatinib provides substantial clinical benefit in HBV-related uHCC, including potential for conversion to surgical resection. Tumor burden emerged as a key predictor of progression. The regimen demonstrated a favorable safety profile, reinforcing its potential as a frontline treatment in HBV-endemic areas.

Background: Early assessment of tuberculosis progression and the efficacy of anti-tuberculosis drugs is crucial for improving disease cure rates. This study aimed to predict the therapeutic efficacy of newly diagnosed sputum-negative but bronchial alveolar lavage fluid (BALF)-positive pulmonary tuberculosis patients after intensive therapy.

Methods: We collected data from 255 patients (178 and 77 in center 1 and 2, respectively) diagnosed with newly diagnosed sputum-negative but BALF-positive pulmonary tuberculosis. Based on imaging and clinical follow-up results, the patients were divided into progression and improvement groups. Radiomics features were extracted from five computed tomography (CT) signs, and feature selection was performed using Pearson correlation analysis and the Least Absolute Shrinkage and Selection Operator (LASSO). Three machine learning models (random forest (RF), support vector machine (SVM), and logistic regression (LR)) were then constructed. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, F1 scores, and Delong tests.

Results: A total of 118 radiomics features were used to construct three models that demonstrated good performance. In the training and test cohorts, the SVM model achieved area under the curves (AUCs) of 0.917 and 0.858, and F1 scores of 0.808 and 0.755, respectively. The RF model showed the highest predictive performance with AUCs of 0.996 and 0.824, and F1 scores of 0.982 and 0.832. The LR model achieved AUCs of 0.927 and 0.808, and F1 scores of 0.867 and 0.747.

Conclusions: Machine learning models based on radiomic features extracted from various CT signs demonstrate potential for predicting the therapeutic efficacy in newly diagnosed pulmonary tuberculosis patients after intensive therapy, providing effective guidance for subsequent treatment.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in children, with an etiology that remains incompletely understood. Recent studies have suggested that the mode of delivery, particularly cesarean section (C-section), may be associated with an increased risk of ADHD. This study aims to examine whether children born via C-section are at increased risk of developing ADHD using both cohort and case-control data.

Methods: We included observational studies (case-control or cohort) that examined the association between mode of delivery and ADHD in children. Inclusion criteria were: (a) ADHD diagnosed using standardized tools; (b) assessment of the relationship between C-section and ADHD; (c) availability of effect estimates (ORs with 95% CIs). Exclusion criteria were: (a) duplicate or overlapping data; (b) unavailable full text; (c) no extractable effect estimates. Literature searches were conducted in PubMed, Web of Science, CNKI, Wanfang, and VIP. Data were extracted using Excel and analyzed in R Studio with the meta, metabias, and metainf packages to pool the adjusted odds ratios (ORs) for the association between C-section and the occurrence of ADHD. Study quality was assessed using the Newcastle-Ottawa Scale (NOS).

Results: A total of 14 studies were included, consisting of six case-control and eight cohort studies across 10 countries in Asia, Europe, the Americas, and Australia. ADHD diagnoses were based on DSM-IV or ICD-10. Most studies adjusted for key confounders such as maternal age (57.14%), child's sex (50.00%), and gestational factors (35.71%). The pooled ORs were 1.44 (95% CI [1.04-1.25]) for case-control studies and 1.12 (95% CI [1.10-1.15]) for cohort studies. All studies scored ≥ 7 on the NOS.

Conclusions: This meta-analysis suggests that C-section is associated with a moderately increased risk of ADHD in children. Both elective and emergency C-sections showed similar effects. However, limitations such as study heterogeneity, potential publication bias, and lack of genetic or biological mechanism data are to be acknowledged. Further research is needed to clarify causality and explore underlying mechanisms.

Objective: To systematically assess the effect of proprioceptive neuromuscular facilitation (PNF), compared to control interventions or other rehabilitation techniques (RT), on pain intensity and knee active range of motion (AROM) in adults with knee osteoarthritis (KOA).

Methodology: This systematic review and meta-analysis was reported in accordance with PRISMA guidelines. A systematic search was conducted in PubMed, Embase, Web of Science, CENTRAL, CNKI, Wanfang, and VIP for studies published from database inception to August 2025. Randomized controlled trials comparing PNF with control interventions or RT were identified in adults with KOA. Primary outcomes were change in pain and change in AROM from baseline to post-intervention. Data were pooled using a random effects model, with risk of bias assessed using the Revised Cochrane risk-of-bias tool (RoB-2) and the certainty of evidence rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

Results: Five studies (n = 201) comparing PNF versus control and four studies (n = 202) comparing PNF versus RT were included. Meta-analysis was conducted only for comparisons between PNF and control. In addition, PNF was qualitatively compared with RT, which included soft tissue mobilization (two randomized controlled trials (RCTs)), neuromuscular exercise (one RCT), and stretching (one RCT). Compared to control interventions, PNF demonstrated significantly greater benefits in pain reduction (standardized mean difference (SMD) = -1.14, p < 0.001) and knee AROM improvement (weighted mean difference (WMD) = 10.08, p < 0.001), albeit the reduction in pain (WMD = -1.66, p < 0.001, four RCTs) did not reach the minimal clinically important difference (MCID). When compared with RT, findings for change in pain were mixed across four RCTs (one favored RT, two showed no difference, one favored PNF); for knee AROM, one favored PNF, while the other showed no difference (no pooling due to methodological heterogeneity).

Conclusions: PNF appears to yield greater improvements in pain reduction and joint mobility compared to control interventions among individuals with KOA. While its efficacy relative to RT remains inconclusive, PNF shows potential as an alternative or adjunct rehabilitation approach. Further high-quality RCTs are needed to determine the effects of PNF on pain reduction and joint mobility in KOA.

As the master orchestrator of integrated stress response, activating transcription factor 4 (ATF4) operates as a central molecular switch that directs cellular fate toward survival or death by regulating genes associated with oxidative stress, endoplasmic reticulum stress, apoptosis, ferroptosis and metabolism. The functional outcome of ATF4 activation is critically dependent on the context: it usually contributes to cellular adaption and survival under mild or transient stress, yet triggers cell death when stress is severe or prolonged. Dysregulation of this dichotomous function has been implicated in a variety of diseases, such as cancer, neurodegenerative disease, metabolic disease, etc., highlighting ATF4 as a potential therapeutic target. Recently, growing evidence has further underscored the dual roles of ATF4 as the guardian or executioner in cardiovascular disorders, such as coronary heart disease, cardiomyopathy, arrhythmia, valvular heart disease, heart failure and cardiovascular aging. Here in this review, we systematically decode the context-dependent opposing roles of ATF4 in cardiovascular diseases and also highlight the underlying regulatory mechanisms, thereby providing a rationale for developing context-specific therapeutic strategies targeting ATF4 for the personalized management of cardiovascular disorders.

Anthracnose disease caused by Colletotrichum fructicola severely compromises the medicinal value and yield of Dendrobium officinale. To elucidate the host metabolic response to pathogen infection, we integrated transcriptomic and metabolomic analyses of D. officinale challenged with C. fructicola. Our results revealed a profound metabolic reprogramming orchestrated by the pathogen, characterized by upregulated flavonoid biosynthesis (e.g., DFR, LDOX activation) and enhanced lipid catabolism (e.g., β-oxidation via LACS, DECR, HACL). Metabolite profiling demonstrated a significant reduction in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) alongside increased free fatty acids, indicating active lipid degradation. Notably, acyl-CoA intermediates linked lipid catabolism to flavonoid production, suggesting a metabolic axis where pathogen-induced lipid breakdown fuels defense-related secondary metabolite synthesis. This study identifies flavonoid and lipid metabolic reprogramming as critical axes in host-pathogen interactions, providing a foundation for developing targeted disease control strategies.

Background: Gynecological malignancies impose a substantial health and economic burden in China. The high cost of treatment often results in considerable financial toxicity, placing economic strain on patients and their families. These challenges can reduce treatment adherence, heighten emotional distress, and impair quality of life. This study aims to assess the degree of financial toxicity among patients with gynecological cancers, evaluate its impact on quality of life, and provide evidence to support the development of targeted clinical interventions to mitigate its adverse effects.

Methods: A convenience sampling approach was employed to recruit 281 patients with gynecological malignancies from two hospitals in Nanjing. A cross-sectional survey was conducted between November 2022 and December 2024. Data were collected using general information questionnaires, the financial toxicity comprehensive scale, and the cancer patient quality-of-life assessment scale.

Results: Data validity was confirmed using Harman's single-factor test (first factor explanatory rate was 30.44%). The mean ± SD total financial toxicity score of the patients was 20.80 ±  7.32 points, with 73% (205/281) experiencing significant financial burdens. The financial resource dimension had the lowest mean score 3.40 ± 1.37 points. Multivariate linear regression analysis indicated that the age of children, family per capita monthly income, treatment costs in the past three months, and marital status were the core influencing factors (adjusted R ² = 0.310). The mean ± SD total quality of life score of the patients was 65.79 ± 11.39 points, and the total financial toxicity score was significantly positively correlated with quality of life (r = 0.553, P < 0.01). Participants had a mean age of 52.27 ± 10.78 years; cervical cancer accounted for the highest proportion (49.5%); 29.2% were unemployed or had resigned due to illness, and 96.8% reported medical expenses exceeding CNY 5,000 (roughly $701.50) in the past three months.

Conclusion: The majority of studied patients experienced financial toxicity, with financial status, family dynamics, and widowhood being key influencing factors.

Background: Obesity is accompanied by chronic low-grade inflammation, largely driven by imbalances in macrophage polarization. While pro-inflammatory M1 macrophages accumulate in adipose tissue and circulation, contributing to insulin resistance and metabolic disruption, alternatively activated M2 macrophages exert anti-inflammatory and tissue-protective effects. Exercise is widely recognized as a non-pharmacological strategy to improve metabolic health; however, the extent to which short-term aerobic training influences systemic macrophage polarization in obesity is not fully understood. This study examined whether a 4-week aerobic exercise intervention alters systemic macrophage polarization in diet-induced obese mice and explored its role in attenuating obesity-related inflammation.

Methods: Male C57BL/6J mice (8 weeks old) were fed either a standard chow diet (Ch) or a high-fat diet (HF; 60% kcal from fat) for 12 weeks. Following obesity induction, HF-fed mice were assigned to either a sedentary (HF-Sed) or exercise-trained (HF-Exe) group. The training protocol involved treadmill running at moderate intensity, performed twice daily, 5 days per week, for 4 weeks. Plasma concentrations of M1-associated markers (TNF-α, IFN-γ , IL-1β, IL-6) and M2-associated markers (IL-10, Arg1, CD163) were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical differences were analyzed using analysis of variance (ANOVA) with post hoc testing.

Results: After 12 weeks of high-fat feeding, mice exhibited approximately 20% higher body weight than chow controls, confirming obesity induction. Four weeks of exercise training did not significantly reduce body weight but improved metabolic indices, including plasma glucose and insulin sensitivity. HF-Sed mice displayed elevated circulating M1 cytokines, whereas HF-Exe mice had significantly lower levels of IL-6, and TNF-α. Conversely, exercise enhanced M2-associated markers, including IL-10, Arg1, and CD163. Thus, aerobic training shifted systemic macrophage polarization away from a pro-inflammatory toward an anti-inflammatory profile, independent of substantial weight loss.

Conclusion: Short-term aerobic exercise is sufficient to promote M2 macrophage polarization and dampen systemic inflammation in obese mice. These findings underline the rapid immunomodulatory potential of exercise and support its role as an effective non-pharmacological approach to counteract obesity-related inflammation and metabolic dysfunction.

Introduction: Down syndrome is associated with muscular hypotonia and feeding problems. The aim was to assess whether postural alterations during mastication had an impact on body composition, food intake and consumption.

Methods: Descriptive cross-sectional study with 48 participants (8-45 years). The OMES-E protocol, anthropometric measurements of body composition and 72 h/3 days intake recording were used.

Results: A total of 35.4% of participants reported being overweight or obese. Statistically significant differences were found in body mass index (BMI) (p = 0.022) and body fat percentage (p = 0.005), both being lower in those participants with postural alteration during mastication. Likewise, a significant relationship was observed between saturated fat intake and postural alteration (p = 0.008). Vitamin D intake was lower than the recommended levels in 77.1% of the participants and vitamin E in 95.8%. Phosphorus (P), iron (Fe) and copper (Cu) were consumed in excess by more than 50% of the sample, especially among those with postural alteration during mastication (58.3%, 45.8% and 45.8%, respectively). As for the food groups, significant differences were recorded in beef consumption, with higher intake in the group with postural alteration.

Conclusions: Individuals with Down syndrome tend to present obesity and/or overweight. Those with a lower BMI and fat percentage presented postural alterations during mastication, associated with a lower overall intake than those without postural alterations. A higher intake of proteins, fats, and B-group vitamins was shown, which points to dietary behaviors that warrant closer attention due to their potential health implications.