Lens epithelial cell-mesenchymal transition (LEC-EMT) is the key process in diabetic cataract (DC). Although PANK4 is known to suppress LEC-EMT, its mechanism remains unclear. This study aims to elucidate the role of PANK4 in DC pathogenesis through the YAP/TAZ pathway.

We established diabetic mice and high-glucose-stimulated LECs. Interventions included PANK4 overexpression/knockdown and YAP inhibitor treatment. Protein expression was analyzed by Western blotting and immunofluorescence. Anterior capsule damage was assessed via slit-lamp after anterior chamber injection of si-PANK4 or YAP inhibitor in diabetic mice. LECs' functional assays included EdU, phalloidin staining, and scratch-wound assays.

PANK4 and EMT markers were significantly upregulated in diabetic mice, and PANK4-overexpression upregulated EMT markers and YAP in LECs. Immunoprecipitation confirmed PANK4-YAP physical interaction in the lens. PANK4-knockdown of LECs and high-glucose-stimulated lens suppressed the expression of α-SMA and YAP, enhanced LECs' proliferation, and reduced the migration. Most importantly, si-PANK4 or YAP inhibition alleviated induced anterior capsule damage in diabetic mice. The si-PANK4 significantly downregulated EMT markers and YAP, and reversed the phosphorylation state of YAP in the lens. YAP inhibitor treatment in PANK4-overexpressing LECs similarly downregulated EMT/YAP markers and replicated the functional effects of si-PANK4 in the lens. High glucose and PANK4-overexpression upregulated HK2, LDHA, and YAP/TAZ expression, and both PANK4-knockdown and YAP inhibition reversed these effects.

Under hyperglycemia, PANK4 activates the YAP/TAZ pathway to upregulate glycolytic enzymes (HK2/LDHA), driving LEC-EMT and early DC progression. In vivo inhibition of PANK4 or YAP alleviates anterior capsule damage, highlighting the PANK4-YAP-glycolysis-EMT axis as a promising therapeutic target for DC.

The objective of this study is to investigate the efficacy of the Shenlian (SL) decoction on regulating cellular pyroptosis and macrophage M1 polarization in the treatment of diabetic nephropathy (DN), and to elucidate its mechanism of action through the use of animal and cellular experiments.

The potential targets for SL decoction were predicted using the TCMSP and Swiss Target databases. The differential genes for DN were obtained using the GeneCards database, and potential mechanisms for the treatment of DN with SL decoction were explored through enrichment analysis. The efficacy of SL decoction in the treatment of DN and its regulation of macrophage polarization and pyroptosis were evaluated in vivo using db/db mice. The RAW264.7 cell line and the TCMK-1 cell line were cultured in vitro. The objective was to investigate the effect of SL decoction on the inhibition of M1 macrophage polarization and scorched death of renal tubular epithelial cells (TECs).

The results of the enrichment analysis indicated that the Toll-like signaling pathway was a principal pathway in the treatment of DN with SL decoction. The results of animal and cellular experiments demonstrated that SL decoction has the potential to enhance renal function in patients with DN, while simultaneously reducing the concentration of serum inflammatory factors. Additionally, it was observed that SL decoction could inhibit the infiltration of macrophages and the polarization of macrophages into the M1 phenotype. Furthermore, the activation of the TLR4 signaling pathway and the pyroptosis of renal tubular cells were also inhibited by SL decoction.

This study employed network pharmacology and in vivo and in vitro experiments to confirm that SL decoction can improve renal function in patients with DN. The results demonstrated that the mechanism of action of SL decoction is related to regulating the M1 polarization of macrophages in the DN kidney and inhibiting the pyroptosis of renal TECs.

Lymphoma is one of the most common malignancies in dogs. In human medicine, complete blood count (CBC)-derived inflammatory ratios, such as the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), have been investigated as potential biomarkers in cancer. However, studies evaluating these parameters in canine lymphoma are limited. This study aimed to compare NLR, MLR and PLR values between dogs diagnosed with lymphoma and healthy controls.

A total of 26 dogs with lymphoma and 10 clinically healthy dogs were included. CBC parameters were analysed, and NLR, MLR and PLR were calculated.

NLR and PLR values were significantly higher in dogs with lymphoma compared to healthy dogs, whereas MLR decreased.

These findings indicate that CBC-derived inflammatory ratios, particularly NLR and PLR, are elevated in dogs with lymphoma and may reflect tumour-associated systemic inflammation. Further studies are needed to evaluate their potential clinical utility.

In this study we report a structured, evidence-based treatment protocol for ocular surface squamous neoplasia (OSSN) by integrating findings from a systematic literature review with expert clinical insights. We performed a two-step methodology. First, a comprehensive systematic review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies on OSSN treatment. Articles were screened based on predefined inclusion and exclusion criteria. Next, a focused group discussion was conducted with expert ophthalmologists to develop a consensus-driven treatment protocol. Discussions were transcribed and thematically analyzed to identify key recommendations for treatment selection and follow-up strategies. Based on the literature review and expert panel consensus, a structured treatment protocol was developed. Surgical treatment is recommended in cases with uncertainty regarding the diagnosis, resource limitations, exclusive corneal involvement, and poor patient compliance with medical treatment or follow-up. Medical treatment with interferon α-2b or 5-fluorouracil is preferred in other scenarios, with agent selection based on side-effect profile and medication availability. Adjuvant therapy is advised when surgical margins are involved. Furthermore, a standardized follow-up schedule is proposed, ensuring long-term monitoring for recurrence. In conclusion, this protocol provides a structured, adaptable framework for OSSN treatment, offering clear guidelines for selecting the appropriate treatment strategy. By balancing evidence-based recommendations with clinical considerations, this protocol aims to optimize patient outcomes.

Immunotherapy based on anti-PD1 inhibitors has significantly improved survival in advanced melanoma. However, a significant proportion of patients do not benefit, and predicting response to immunotherapy remains an area of unmet need. Our group previously defined an immune signature able to predict response to anti-PD1 inhibitors in this scenario.

In this study, we analyzed two cohorts of patients with advanced melanoma treated with anti-PD1 inhibitors: the GEM cohort, previously used to validate our immune signature, and Campbell's cohort, which contains data about different immunotherapy schemes. Using the 107 genes that compose our immune signature and consensus clustering, samples were classified as immune-low or immune-high. Then, CIBERSORTx and Ecotyper were used to estimate the proportion of each immune cell type and carcinoma ecotypes in both cohorts.

We confirmed that the immune-low group includes mostly patients who do not response to anti-PD1 inhibitors. We also studied the distribution of carcinoma ecotypes in the immune-high and immune-low groups defined by our immune classification. Ecotypes CE9 and CE10 clustered in the immune-high group, with good response to treatment. The use of combination immunotherapy improved response rate both in immune-low and immune-high tumors. The immune-high group contained a higher number of CD8 T cells, B memory cells and T follicular helper cells.

Our immune-based classification defines an immune-low group of tumors with poor response to anti-PD1 inhibitors. This immune classification is related to carcinoma ecotypes. Finally, a use of a combo scheme improves the rates of response both in immune-high and low groups but in the case of immune-low tumors, our results suggests that a combo treatment approach could be an adequate strategy and should be further explored in these patients. Altogether, our results support the utility of our immune signature in the prediction of response to anti-PD1 inhibitors in advanced melanoma.

Tumor-draining lymph nodes (LNs) are critical for initiating and maintaining antitumor immunity. However, systematic LN dissection (LND) remains the standard surgical procedure for lung cancer. This study aimed to investigate the immunological impact of tumor-draining LND on systemic T cell subsets.

We prospectively analyzed perioperative peripheral blood and resected LN samples from patients with early-stage lung adenocarcinoma who underwent lobectomy with systematic LND (systematic LND group) or wedge resection without LND (LN-preserving group). Perioperative immune cell dynamics were comprehensively profiled using mass cytometry.

Unlike conventional CD4⁺ and CD8⁺ T cell subsets, Th7R (CXCR3^±CCR4^-CCR6⁺ CD62L^lowCD4⁺ T cell), a Th1-like CD4⁺ T cell cluster essential for antitumor immunity, consistently decreased in peripheral blood after tumor resection in both groups (p = 0.0016 and p = 0.0033). This decline was significantly milder in the LN-preserving group than in the systematic LND group (p = 0.0153). In LN analyses, Th7R percentages were significantly higher in hilar, interlobar, and peripheral LNs than in subcarinal and other mediastinal LNs (p = 0.0148). Th7R percentages in resected LNs strongly and negatively correlated with postoperative changes in peripheral blood (r = -0.857, p = 0.0137). Furthermore, greater declines in Th7R in peripheral blood were associated with postoperative oncological disease events.

Preserving LNs contributes to maintaining systemic antitumor immunity after surgery for early-stage lung cancer. Hilar, interlobar, and peripheral LNs may serve as primary reservoirs and supply sources of Th7R. In early-stage disease, these findings suggest a potential immunological benefit of LN-preserving strategies.

The widespread use of cross-sectional imaging has increased the incidental detection of small renal masses (SRMs). In this context, overtreatment represents a major concern, particularly for lesions < 2 cm. Most evidence derives from retrospective registries, whereas prospective data remain limited.

This multi-center, prospective, non-randomized clinical trial was conducted in five European centers between January 2015 and July 2021. Seventy-six patients aged > 50 years with asymptomatic, unilateral SRM < 2 cm were enrolled and followed under a structured prospective active surveillance (AS) protocol with periodic axial imaging. Active treatment was recommended according to predefined progression criteria or patient preference. The primary endpoint was event-free survival (EFS); secondary endpoints included treatment-free survival (TFS), overall survival (OS), and cancer-specific mortality (CSM).

69 patients were included in the analyses. After a median follow-up of 88 months, 8-year EFS and TFS were 66% and 83%, respectively. 17% of patients required active treatment, mainly due to tumor growth. The 8-year OS and CSM were 88% and 9.6%. One patient died of metastatic RCC. Shorter tumor doubling time (DT) (< 12 years) and high RENAL score were significantly associated with higher risks of event and treatment. Endophytic tumors, and higher PADUA score also predicted adverse outcomes.

Long-term follow-up confirms AS as the standard initial option for selected patients with SRMs ≤ 2 cm, with a low rate of progression and optimal survival rates. Tumor DT and mass location should be considered in clinical decision-making to identify patients who will deserve a deferred treatment in case of progression.

Some novel anticancer agents are associated with drug-induced interstitial lung disease (ILD), a critical and potentially fatal adverse event. Lung cancer patients appear particularly susceptible, yet the risk and clinical characteristics remain incompletely analyzed.

To comprehensively evaluate ILD risk and characteristics induced by novel anticancer agents in non-small cell lung cancer (NSCLC) using large-scale real-world data.

A retrospective pharmacovigilance study based on spontaneous adverse event reports.

Data from 2014 to 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). Reports of NSCLC patients who developed ILD during treatment with FDA-approved novel anticancer agents (immune checkpoint inhibitors, targeted therapies, antibody-drug conjugates). The reporting odds ratio (ROR) was used to assess the disproportionate reporting signals for each drug. Statistical significance was defined when the lower 95% confidence interval (CI) exceeded 1 with at least three reports.

A total of 4712 NSCLC cases were analyzed. Eight agents were identified with positive signals for ILD: ROR and 95% CI for nivolumab was 1.28 (1.20-1.38), pembrolizumab 1.47 (1.36-1.59), durvalumab 7.38 (6.90-7.89), atezolizumab 1.25 (1.12-1.39), ipilimumab 1.96 (1.74-2.21), tremelimumab 3.58 (1.97-6.50), trastuzumab-deruxtecan 3.14 (2.29-4.30), osimertinib 1.12 (1.03-1.23). The median onset time was 33 days, with 48.59% of ILD events occurring within the first month. The fatal cases experienced a significantly shorter onset time than non-fatal cases. Older age, male sex, and lower body weight were identified as factors affecting ILD, whereas lower body weight, male sex, and a higher number of concomitant drugs were linked to increased mortality.

Our study identifies positive signals for ILD with eight novel antineoplastic agents in NSCLC, including nivolumab, pembrolizumab, durvalumab, atezolizumab, ipilimumab, tremelimumab, trastuzumab-deruxtecan, and osimertinib, highlights the importance of monitoring during the first month of therapy, and identifies older male patients with lower body weight as a high-risk group.

Small intestinal adenocarcinoma (SIA) is a rare cancer with a poor prognosis. Optimal treatment strategies are unclear as biological understanding of the disease is limited and randomized controlled trials are lacking. Current management is based on protocols for other gastrointestinal cancers. Therefore, the AdenoCarcinoma of the Small Intestine (ACSI) cohort was initiated, a subcohort of the nationwide Prospective Dutch ColoRectal Cancer cohort (PLCRC) study. The ACSI cohort aims to provide a large-scale, prospective SIA cohort, where clinical and molecular data will be combined to improve knowledge on tumor biology, treatment responsiveness, disease outcome and patient reported outcomes (PROs). Patient/material and methods: All adult SIA patients in the Netherlands are eligible for inclusion. Nationwide inclusion is facilitated by 68 hospitals. Clinical data are collected, as well as optional PROs, pathology- and blood samples.

Until June 2025, 143 patients have been enrolled. Data of the first 105 patients show a median age of 65 years (interquartile range 58-73) at diagnosis with a slight male predominance (60%). Most tumors are located in the duodenum (57%) and 27% of patients present with stage IV disease, with a majority having single-site metastases (64%). Primary tumor resection is performed in 80%, while systemic treatment is administered in 42%. Four patients did not receive any anti-tumor treatment (14%). Mismatch repair deficiency is detected in 28% of patients.

The ACSI cohort enables structured national collection of clinical data, tumor samples and PROs of SIA patients. These data provide a valuable source for further research and improvement of care for this patient group.

Cervical cancer remains one of the most preventable yet deadly diseases affecting women in low-resource and conflict-affected regions such as Syria. Persistent challenges including limited access to health care, disrupted health infrastructure, sociocultural taboos, and inadequate health education have severely restricted the implementation and uptake of screening programs. Understanding the multifaceted determinants of women's awareness, perceptions, and health-seeking behavior is essential for designing sustainable, context-sensitive prevention strategies.

This study aimed to evaluate Syrian women's knowledge, attitudes, and screening practices toward cervical cancer and to identify demographic, educational, and psychosocial predictors influencing these domains. It also sought to explore the paradoxical role of education in shaping self-efficacy, awareness, and screening-related attitudes within this population.

A descriptive cross-sectional design was employed.

Data were collected between November 2024 and May 2025 in Damascus, Syria, using a validated self-administered electronic questionnaire. A total of 606 women aged 15 years and above participated voluntarily. The questionnaire assessed knowledge, attitudes, and self-efficacy related to cervical cancer and screening behaviors. Descriptive statistics and linear regression analyses were performed to examine associations between sociodemographic factors and outcome measures.

Although 49% of respondents demonstrated moderate knowledge, only 10% had ever undergone a Pap smear. Major barriers included embarrassment (59%), fear of discomfort (51%), and financial limitations (21%). Higher education significantly predicted better knowledge (p < 0.05) but was paradoxically linked to less favorable attitudes and lower self-efficacy. Greater knowledge correlated positively with self-efficacy, while older age showed a negative association.

A profound disconnect persists between awareness and screening behavior among Syrian women. Interventions must extend beyond information delivery to address cultural, emotional, and economic barriers through comprehensive, community-based, and empowerment-oriented public health initiatives.