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Although dipeptidyl peptidase-4 inhibitors (DPP4is) are widely used in the treatment of diabetes, a known risk factor for renal function decline, the potential association between DPP4i use and acute kidney injury (AKI) remains controversial. This study aimed to evaluate the association between DPP4i and AKI while considering the concomitant use of inducers of AKI in patients with diabetes. Data from the US Food and Drug Administration Adverse Event Reporting System were analyzed, focusing on seven DPP4is in daily use, namely alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin. Disproportionality analysis was performed to determine the association between DPP4i use and AKI using reporting odds ratios and information components, stratified by age groups, in the presence or absence of 10 types of AKI inducer used concomitantly. Of 215,051 reports, a positive association between DPP4i and AKI was found for linagliptin, sitagliptin, and vildagliptin in the overall analysis. Age-stratified analysis revealed associations between the DPP4is linagliptin, saxagliptin, sitagliptin and vildagliptin and AKI in the middle-aged group of patients, whereas only sitagliptin and vildagliptin were associated with AKI in the elderly group. Exclusion of concomitant renin-angiotensin-aldosterone system inhibitors, diuretics, or non-steroidal anti-inflammatory drugs altered signal detection for certain DPP4is, with these changes varying by age group. This study suggests that some DPP4is, including linagliptin, sitagliptin and vildagliptin, are associated with AKI, even without concomitant use of an AKI inducer. Given the widespread use of DPP4is and the severity of AKI, clinicians should be sufficiently informed about their potential relationship.

Viral infections in the kidney activate innate immunity via double-stranded RNA (dsRNA) sensors such as retinoic acid-inducible gene-I (RIG-I). This induces the expression of interferons and interferon-stimulated genes (ISGs), including ISG15. Similarly to ubiquitin, ISG15 functions by binding to target proteins and exerting antiviral effects through ISGylation. ISG15 is secreted extracellularly and exerts antiviral effects. Ubiquitin-like modifier-activating enzyme 7 (UBA7) initiates ISGylation, whereas ubiquitin-specific protease 18 (USP18) removes ISG15 from conjugated proteins. Both RIG-I and ISG15 are involved in antiviral responses and renal fibrosis. However, their interaction during kidney inflammation remains unclear. Primary human renal proximal tubule epithelial cells (hRPTECs) were stimulated with polyinosinic polycytidylic acid [poly(I:C)] to mimic viral dsRNA. The mRNA and protein levels were analyzed using RT-qPCR, western blotting, or ELISA. Poly(I:C) upregulated the mRNA and protein expression of RIG-I, ISG15, UBA7, and USP18. RIG-I, ISG15, and UBA7 levels increased over time, whereas USP18 levels decreased rapidly. UBA7 knockdown reduced ISGylation, whereas USP18 knockdown enhanced it. Silencing RIG-I decreased ISG15 conjugates, extracellular ISG15, and protein levels of UBA7 and USP18. RIG-I promotes ISGylation by modulating UBA7, USP18, and ISG15 in renal proximal tubule epithelial cells. RIG-I may help maintain ISGylation homeostasis by balancing the activity of these molecules and preventing the excessive accumulation of free ISG15 or ISGylated proteins. These findings highlight the dual role of RIG-I in antiviral defense and its potential contribution to renal fibrosis, thereby providing insights into therapeutic strategies to balance immunity and kidney protection.

Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis. Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on cancer-related pathways. Irisin, derived from the precursor FNDC5 upon PGC-1α activation in skeletal muscle, regulates cancer-associated pathways by activating AMP-activated protein kinase (AMPK), inhibiting mammalian target-of-rapamycin (mTOR), modulating phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor kappa B (NF-κB) signaling, and influencing transforming growth factor beta (TGF-β) activity. These actions reduce chronic inflammation, tumor proliferation, angiogenesis, and epithelial-mesenchymal transition, while enhancing apoptosis and metabolic balance. Preclinical studies demonstrate irisin's capacity to limit BC cell viability, migration, and metastasis. Clinically, higher circulating irisin levels correlate with reduced tumor aggressiveness, fewer metastases, and better survival, though tumor may overexpress irisin as a local adaptive response. Regular moderate physical activity appears most effective in stimulating irisin secretion, although optimal exercise parameters remain to be determined. Irisin exerts multifaceted anticancer effects and holds promise as a biomarker and therapeutic target in BC. Its role as a mediator of exercise benefits supports the inclusion of regular moderate physical activity in BC prevention and prognosis strategies. Further research is needed to define clinical applications and optimal exercise regimens for maximizing irisin potential.

Immunosuppressive and nutritional treatments have improved the prognosis of Cronkhite-Canada syndrome (CCS). CCS-associated polyps are benign and categorized into hamartomatous, inflammatory, hyperplastic, and adenomatous polyps; however, the development of gastrointestinal cancer is considered the most significant prognostic factor for CCS. Although the adenoma-carcinoma sequence and inflammation-associated carcinogenesis are two major pathways for the development of colorectal cancers (CRCs), it remains largely unknown which pathway plays critical roles in the development of CRCs in CCS. Inflammation-associated carcinogenesis might be involved in the development of CRCs associated with CCS because CCS-associated polyps are characterized by submucosal infiltration of immune cells. Given the fact that proinflammatory cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α underlie the pathogenesis of inflammation-associated carcinogenesis, we examined the involvement of proinflammatory cytokines in the transformation of CCS-associated polyps into CRCs. Three cases of CCS were enrolled: two cases with concurrent CRCs and a single case without CRC. mRNA was isolated from non-cancerous CCS-associated polyps and subjected to reverse transcription quantitative polymerase chain reaction to determine expression of proinflammatory cytokines. Colonic biopsy samples were isolated from non-tumor portions of patients with colonic adenoma to determine mRNA expression of proinflammatory cytokines in healthy colonic mucosa. Higher mRNA expression of IL-6, but not IL-1β or TNF-α, in non-cancerous CCS-associated polyps was observed in two patients with CCS and concurrent CRCs as compared with four healthy colonic mucosal samples and a patient with CCS without CRC. IL-6-mediated inflammation-associated carcinogenesis might be involved in the transformation of CCS-associated polyps into CRC.

Poly lactic acid microsphere fillers stimulate neocollagenesis, but aggregation can yield heterogeneous remodeling. We compared poly-L-lactic acid (PLLA)- and poly-D,L-lactic acid (PDLLA)-based fillers to connect stereochemistry with microsphere stability, dispersion, and in vivo outcomes. Poly lactic acid/sodium hyaluronate composite fillers were analyzed by scanning electron microscopy, nuclear magnetic resonance, differential scanning calorimetry, and micro-compression. Dispersion-aggregation-redispersion in saline was quantified over 3 days by optical microscopy with circularity-based analysis. In SKH mice, 100 μl filler was injected subcutaneously. Projection volume was measured at baseline (day 0) and at 2, 4, 8, and 12 weeks post-injection using phase-shift rapid in vivo measurement of skin (PRIMOS). Tissue response was observed at the same time points using hematoxylin and eosin, Masson's trichrome, and macrophage immunofluorescence. PLLA microspheres remained discrete after saline dispersion and excipient removal, whereas PDLLA particles deformed and collapsed into compact clusters. PLLA particles (median 49.10 μm) were larger than PDLLA particles (median=19.85 μm) and showed semicrystalline differential scanning calorimetry features (glass transition temperature=60.88°C, cold crystallization temperature=94.2°C, melting temperature=169.18°C), while PDLLA was predominantly amorphous. PDLLA formed larger, poorly re-dispersible aggregates (median cluster=458.06 μm) than PLLA (median cluster=380.02 μm). In vivo, volume declined through week 4 then recovered. PLLA rebounded more uniformly with greater collagen area and weaker inflammatory and macrophage signals than PDLLA. PLLA crystallinity and mechanical robustness support re-dispersibility and more homogeneous collagen remodeling, whereas PDLLA aggregation is linked to heightened inflammation and reduced collagen deposition. Collectively, these findings suggest that maintaining microsphere integrity and dispersion is a key, actionable determinant of more uniform biostimulatory outcomes in PLA-based fillers.

Autophagy plays a crucial role in maintaining cellular homeostasis and has been implicated in the pathogenesis of knee osteoarthritis (OA). However, data on radiographic stage-dependent transcriptional variation of autophagy-related genes in patients with knee OA, particularly using peripheral blood samples, remain limited. The aim of this study was to evaluate whether disease severity was associated with stage-dependent changes in the expression of selected autophagy-related genes within a patient cohort. A total of 200 patients diagnosed with knee OA were included in the study. Disease severity was classified according to the Kellgren-Lawrence radiographic grading system. Peripheral blood samples were collected, and the expression levels of selected autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction [autophagy-related 5 (ATG5), ATG7, unc-51-like kinase 1 (ULK1), microtubule-associated protein 1 light chain 3 beta (LC3B), WD repeat domain phosphoinositide-interacting protein 1 (WIPI1), neighbor of BRCA1 gene 1 (NBR1), forkhead box O3 (FOXO3), transcription factor EB (TFEB)]. Relative gene expression was calculated using the &#x394;Ct method, and comparisons were performed across radiographic stages. Associations between gene expression levels and systemic inflammatory markers were also assessed. Significant stage-dependent differences were observed in the expression of ULK1, TFEB, WIPI1, and NBR1 (p<0.05), with higher &#x394;Ct values (reduced relative expression) in advanced radiographic stages compared with early-stage disease. In contrast, ATG5, ATG7, LC3B, and FOXO3 expression remained stable across radiographic stages. Furthermore, no significant associations were observed between expression of autophagy-related genes and systemic inflammatory status, as assessed by C-reactive protein levels. In patients with knee OA, regulatory and early autophagy-related genes exhibit radiographic stage-associated transcriptional alterations in peripheral blood, while expression of core autophagy machinery genes remain relatively stable. These findings suggest that disease severity is associated with selective transcriptional changes in autophagy-related pathways within the OA patient population and support further investigation of stage-dependent molecular patterns in knee OA.

We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR. A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls &#x2265;1 (upregulated; 20 genes) or &#x2264;-1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly different (71%). Expression of matrix metalloproteinase 9, TIMP metallopeptidase inhibitor 3, collagen type I &#x3b1; 1 chain (COL1A1), COL6A3, COL15A1, intercellular adhesion molecule 1 (ICAM1), ICAM2, decorin, endoglin, apolipoprotein D (APOD), APOE, phospholipid transfer protein, calcium and integrin binding 1 (CIB1), phospholipase A2 group IIA, von Willebrand factor, serpin family B member 6 (SERPINB6), urokinase-type plasminogen activator, H19, C-C motif chemokine ligand 2, and platelet-derived growth factor receptor beta was upregulated in AAA vs. normal aorta. Expression of collagen type IV &#x3b1; 4 chain (COL4A4), COL11A2, gap junction protein &#x3b1; 1 (GJA1), biglycan, integrin subunit &#x3b1; 8, galectin-1, low-density lipoprotein receptor-related protein 1, acetyl-CoA acyltransferase, serpin family E member 1, melanoma cellular adhesion molecule, sodium channel epithelial 1 subunit beta (SCNN1B), natriuretic peptide receptor 1 (NPR1), superoxide dismutase 3, actinin &#x3b1; 1 (ACTN1) and cardiac phospholamban (PLN) was downregulated. Eleven genes differentially expressed (p&#x2264;0.05) in AAA lesions vs. normal aortas were not reported previously: upregulated: COL6A3, COL15A1, ICAM2, APOD, CIB and SERPINB6; downregulated: GJA1, SCNN1B, NPR1, ACTN1 and PLN. Remaining results confirmed previous reports regarding 21 genes differentially expressed in AAA. qRT-PCR results were in general in agreement with microarray results.

Decompressive craniectomy (DC) is a life-saving intervention performed in patients with severe neurological deterioration; however, early postoperative mortality remains high and reliable biochemical predictors are not well defined. This study aimed to identify early clinical and perioperative biochemical predictors of 30-day mortality in patients undergoing DC. This single-center retrospective cohort study included 102 patients who underwent DC between 2019 and 2024. Demographic, clinical, radiological, and biochemical parameters including sodium, potassium, hematocrit, international normalized ratio (INR), C-reactive protein (CRP), and neutrophil to lymphocyte ratio (NLR) were analyzed. The primary outcome was 30-day mortality. Univariable analyses were conducted using Chi-square and t-tests. Multivariable logistic regression models were constructed using a hierarchical approach to evaluate independent predictors. Model performance was assessed using likelihood ratio Chi-square, Hosmer-Lemeshow goodness-of-fit statistics, and area under the receiver operating characteristic curve (AUC). Thirty-day mortality occurred in 70.6% of patients. In the multivariable model, preoperative INR >1.20 (OR=25.60; 95% CI=1.89-345.82; p=0.015) and discharge NLR >3.13 (OR=5.19; 95% CI=1.01-26.66; p=0.048) were identified as strong independent biochemical predictors of mortality. Conversely, preoperative GCS 8-13 was independently associated with improved short-term survival (OR=0.16; 95% CI=0.03-0.89; p=0.036). The predictive accuracy of the model significantly improved after adding biochemical variables, with Pseudo R&#xb2; increasing from 0.115 to 0.252 and an AUC of 0.826, indicating good discrimination and calibration (Hosmer-Lemeshow p=0.765). Preoperative INR and discharge NLR are strong independent predictors of early mortality after decompressive craniectomy, while preoperative GCS remains a key indicator of improved survival. These routinely available biochemical markers may enhance postoperative risk stratification and inform clinical decision-making in critically ill neurosurgical patients.

Pain assessment and management in children remain challenging, particularly in those with neurodevelopmental disorders. Attention-deficit/hyperactivity disorder (ADHD) is characterized by alterations in attention, executive function, emotional regulation, and reward processing. These domains are also critically involved in pain perception and expression. Emerging evidence suggests that children with ADHD may experience pain differently, display atypical pain behaviors, and face substantial challenges in pain assessment and treatment. However, the literature on pediatric ADHD and pain is fragmented across experimental, clinical, and behavioral studies. This narrative review critically examines the neurobiological, psychological, and clinical interactions between ADHD and pain in children. We discuss proposed mechanisms linking ADHD to altered pain processing, summarize evidence on pain perception and expression, explore common pain conditions where this interaction is clinically relevant, and analyze challenges in pain assessment and management. Finally, we identify knowledge gaps and propose future directions toward function- and child-centered pain care. By considering ADHD as a modifier of pain experience and a potential contributor to pain chronification rather than a mere comorbidity, this review highlights the importance of adapting pain assessment and management strategies to the specific neurodevelopmental profile of pediatric patients.

Albumin is abundant in human plasma and has been widely studied in cancer mainly in the context of systemic nutrition or the tumor microenvironment; however, the clinicopathologic significance and intracellular role of tumor-cell albumin in gastric adenocarcinoma remain unclear. We analyzed 187 patients who underwent gastrectomy for gastric adenocarcinoma between 2000 and 2010. Albumin expression was evaluated by immunohistochemistry on tissue microarrays and classified as high versus low based on intensity relative to intra-tumoral stromal cells. Associations with clinicopathologic variables were examined, and disease-free survival (DFS) and disease-specific survival (DSS) were assessed using Kaplan-Meier and Cox regression. Albumin mRNA/protein expression was examined in three metastatic gastric cancer cell lines, and functional assays (wound healing and proliferation) were performed after siRNA-mediated albumin knockdown in Hs746T cells. High albumin expression was significantly associated with larger tumor size and advanced T and N stages. Albumin expression was not significantly associated with DFS or DSS in univariate or multivariate analyses, whereas T stage and N stage remained independent prognostic factors. In vitro, albumin knockdown significantly impaired migration and reduced proliferative capacity, despite limited detectable reduction in protein levels. Tumor-cell albumin correlates with gastric cancer progression and functionally contributes to motility and growth at the intracellular level, supporting its role as a marker of aggressive tumor biology rather than an independent prognostic biomarker.

High-dose vitamin D supplementation is increasingly used to achieve extraskeletal effects, but its safety regarding mineral metabolism remains under discussion. This study assessed the effects of vitamin D on serum calcium, magnesium, and parathyroid hormone (PTH) concentrations in young healthy individuals. Sixty-five healthy volunteers received cholecalciferol drops in doses ranging from 1,000 to 8,000 IU/day across two winter seasons. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], calcium, magnesium, and PTH were measured at defined intervals. Supplementation resulted in a dose-dependent increase in serum 25(OH)D, reaching a maximum of 208.5 nmol/l. Despite the high intake, all measured parameters remained within physiological ranges. A significant inverse association between 25(OH)D and PTH levels confirmed physiological suppression of PTH at higher vitamin D concentrations, though all values stayed within reference limits. The absence of clinically relevant disturbances in calcium, magnesium, or PTH levels supports the safety of high-dose vitamin D supplementation when appropriately monitored in young healthy adults, even at the upper limits of therapeutic dosing. These findings highlight the need for further research to delineate the long-term effects of high-dose vitamin D supplementation on mineral metabolism across diverse patient populations.

Intravesical bacillus Calmette-Gu&#xe9;rin (BCG) therapy is the standard adjuvant treatment for high-risk non-muscle-invasive bladder cancer (NMIBC). However, the impact of advanced age, particularly &#x2265;80 years, on oncological outcomes of BCG therapy remains controversial. This study evaluated age-stratified outcomes and real-world BCG delivery in patients with NMIBC. We retrospectively reviewed 120 consecutive patients with NMIBC who initiated intravesical BCG therapy between June 2019 and May 2025 at a single center. Patients were stratified by age at BCG initiation into <80 years (n=91) and &#x2265;80 years (n=29). High-risk recurrence-free survival (HR-RFS), progression-free survival (PFS), metastasis-free survival (MFS), and overall survival (OS) were assessed. HR-RFS was defined as the time from BCG initiation to recurrence of high-risk NMIBC or disease progression. Survival outcomes were estimated using the Kaplan-Meier method and compared between groups. Baseline clinicopathological characteristics and the rate of achieving the institution-defined minimum BCG exposure were similar between the two age groups. During a median follow-up of 33.5 months, there were no significant differences in HR-RFS (p=0.803), PFS (p=0.700), MFS (p=0.750), or OS (p=0.065) between the groups. Although HR-RFS was numerically lower in the &#x2265;80 years group, progression to muscle-invasive disease and distant metastasis remained infrequent and comparable between groups. In this real-world cohort, intravesical BCG therapy achieved comparable oncological outcomes in patients aged &#x2265;80 years and younger patients with NMIBC. Chronological age alone was not associated with inferior clinically meaningful disease control, supporting BCG use in older patients when clinically indicated, with treatment decisions guided by tolerability and patient preference.

Hip replacement is one of the most common and successful surgeries of our time. However, with increasing numbers of total hip arthroplasties, postoperative complications due to inadequate cup positioning are rising. Accurate measurement of acetabular cup inclination and anteversion is critical for optimal outcomes. While various measurement systems exist, they often require additional hardware, specialized training, or lack integration across the care continuum. This study aims to develop and validate software for automated measurement of acetabular cup positioning, comparing its performance to standard CAD measurements. The geometric basis for analyzing the acetabular cup is that a hemisphere in 2D projection forms an ellipse, described by a conic section equation. We developed a Python-based software utilizing computer vision techniques for edge detection and ellipse fitting to determine anteversion and inclination from standard radiographs. The software was trained and validated using X-ray images of a pelvic phantom with a conventional acetabular cup (Allofit, Zimmer Biomet) at various predefined angles. CAD software (MediCAD) served as the validation standard. The intraclass correlation coefficient (ICC) quantified agreement between methods. A total of 140 AP X-ray images were analyzed. Inclination averaged 50.69&#xb0;&#xb1;15.86&#xb0; with our software versus 49.40&#xb0;&#xb1;15.24&#xb0; with CAD. Anteversion averaged 14.36&#xb0;&#xb1;9.08&#xb0; versus 14.75&#xb0;&#xb1;8.88&#xb0; with CAD. The ICC was 0.994 for inclination and 0.992 for anteversion (both p<0.001), demonstrating excellent agreement. Our computer-assisted measurement technique demonstrates excellent concordance with standard methodologies while offering workflow advantages. These results provide a foundation for implementation within computer vision models for automated spatial positioning recognition. Future development will focus on enhancing automation, validating across diverse populations and implant designs, and comparing with 3D computed tomography (CT) measurements.

Periprosthetic joint infection (PJI) remains one of the most challenging complications after arthroplasty, largely due to biofilm formation on prosthetic surfaces, which protects bacteria from antibiotics and host defenses. This study investigated whether a freezing nitrogen-ethanol composite (FNEC), a semisolid cryogenic material combining liquid nitrogen and ethanol, can effectively eradicate Staphylococcus aureus biofilms on prosthetic components. Biofilms of S. aureus were established on plastic spacers and metallic knee prostheses. Specimens were treated for 15 min with 75% ethanol, liquid nitrogen (LN), or FNEC. Bacterial viability was assessed using LIVE/DEAD fluorescence staining, while eradication efficacy was confirmed through broth inoculation and optical-density (OD600) measurements. Additional indirect-exposure experiments evaluated the contribution of FNEC's freezing effect, and time-dependent testing determined the minimal effective exposure duration. FNEC achieved the most complete biofilm eradication across both plastic and metallic surfaces. LIVE/DEAD staining demonstrated widespread cell death with minimal residual viability. Broth cultures from FNEC-treated samples remained clear, with OD600 values indistinguishable from sterile controls, whereas LN and untreated samples showed significant bacterial growth. Indirect experiments confirmed that FNEC's cryogenic effect alone substantially contributed to bacterial death. Time-course analysis revealed that a 5-min FNEC exposure was sufficient for complete sterilization. FNEC exhibited potent bactericidal and biofilm-removal capability, outperforming ethanol and LN alone. Its combined chemical and cryogenic effects enabled rapid and complete eradication of S. aureus biofilms within 5 min. These findings support FNEC as a promising adjunctive strategy for intraoperative biofilm management and may facilitate single-stage revision surgery for PJI.

SARS-CoV-2 infects the oral and salivary glandular epithelia, leading to release of progeny viruses to shed into saliva. This causes the persistent spread of COVID-19 since the outbreak of the Omicron variants. Viral spread may be mainly attributable to the aerosol transmission of cell-free virions in saliva droplets <5 &#x3bc;m in diameter. However, no data exist on how cell-free virions in the saliva change over time. We, therefore, examined temporal changes in the proportion of cell-free virions shed into saliva relative to whole saliva in individuals infected with the SARS-CoV-2 Omicron variant. This study analyzed three indices, total viral load in whole saliva, cell-free virion load in centrifuged supernatant, and "salivary viral load ratio", in 14 subjects infected with SARS-CoV-2 Omicron variant on days 1, 4, and 7 after symptom onset. The "saliva viral load ratio" was calculated by dividing the number of cell-free virions in the centrifuged supernatant by the total number of viruses detected in the whole saliva. The viral load in whole saliva and in the salivary supernatant considerably decreased with time since day 1. However, unexpectedly regarding "salivary viral load ratio," no substantial difference was observed among the collection dates. Determining the chronological dynamics of salivary cell-free viral load and "salivary viral load ratio" is important for monitoring aerosol transmission. Individuals infected with Omicron variants remain potent to render aerosol transmission until COVID-19 is cured. This will alert health care providers to consider "salivary viral load ratio" as an indicative measure of the likelihood of aerosol transmission in the very early stages of viral infection outbreaks.

Acute kidney injury (AKI) is one of the most frequent adverse effects induced by cisplatin (CDDP). One clinical indicator of CDDP-induced AKI is urine output, which reflects water balance; however, urine collection can expose healthcare workers to anticancer drugs. An alternative monitoring approach for CDDP-induced AKI is weight-based assessment of fluid balance. Although previous studies have evaluated the relationship between body weight change and CDDP-induced AKI, few have evaluated the amount of water ingested. Therefore, we evaluated water intake, urine output, and body weight changes in patients treated with CDDP to determine the utility of weight monitoring as an indicator of fluid balance during CDDP-based chemotherapy. We evaluated 15 patients who received CDDP-vinorelbine as postoperative adjuvant chemotherapy for non-small cell lung cancer from March to December 2019. Patients recorded their oral fluid intake, and body weight changes were evaluated on days 2-4 relative to baseline on day 1. No cases of CDDP-induced AKI occurred. Compared with day 1, urine output decreased on day 2 but recovered on day 3. Body weight fluctuations were highest (+3.6 kg) on day 3 and started decreasing on day 4. Serum creatinine and estimated glomerular filtration rate did not differ significantly pre- and post-chemotherapy. A positive correlation was observed between water balance and next-morning weight change (r=0.68). Weight monitoring may reduce healthcare workers' exposure to anticancer agents while serving as a practical indicator of fluid balance during CDDP-based chemotherapy.

Pyogenic spondylodiscitis causes rapid endplate destruction followed by bone remodeling; however, the time-course of bone loss and recovery remains incompletely defined. This study aimed to characterize longitudinal changes in vertebral bone and intervertebral disc pathology in a rat tail pyogenic spondylodiscitis model. Male Sprague-Dawley rats (n=16) were allocated to 2-, 4-, or 6-week observation groups. Staphylococcus aureus ATCC 29213 (107 CFU/ml, 100 &#x3bc;l) was injected into the C6/7 disc space (Discitis segment), and phosphate-buffered saline (100 &#x3bc;l) was injected into C9/10 as an internal Control segment. Micro-computed tomography was performed at baseline and at sacrifice to quantify the bone destruction rate, disc height ratio, cancellous Hounsfield units (HU), and trabecular microarchitecture (bone volume fraction, trabecular thickness, trabecular number, and trabecular separation). Histology (TRAP and osteocalcin staining) and bone histomorphometry [osteoclast surface per bone surface (Oc.S/BS), osteoclast number per bone surface (Oc.N/BS), and osteoblast surface per bone surface (Ob.S/BS)] were evaluated. The bone destruction rate was significantly higher in the Discitis segment than in the Control segment at all time points, indicating persistent endplate damage. The disc height ratio decreased at 2 weeks but did not differ from controls at 4-6 weeks. Cancellous HU and trabecular parameters showed a biphasic pattern: decreased bone mass at 2 weeks, followed by recovery/reconstruction at 4-6 weeks. Histomorphometry demonstrated increased osteoclast activity (Oc.S/BS, Oc.N/BS) and osteoblast surface (Ob.S/BS) in the acute phase, with osteoclast indices decreasing over time, whereas osteoblast surface remained relatively elevated. This model demonstrated a biphasic bone metabolic response characterized by increased osteoclast-mediated bone resorption followed by bone formation and trabecular remodeling. Moreover, this model may serve as an experimental platform to investigate the optimal timing and strategies of therapeutic interventions.

Neuroendocrine tumors (NETs) represent a complex, heterogeneous group of cancers with unique characteristics. Early detection and multiple modalities therapies such as surgical intervention or symptom control (e.g., somatostatin analogs). Treatment for late-stage disease including combining local treatment (surgery, radiofrequency ablation, selective internal radiation therapy, trans-hepatic arterial chemo-embolization/trans-hepatic arterial embolization) with that for systemic disease, such as peptide receptor radionuclide therapy, chemotherapy and targeted therapy, are essential for managing symptoms and improving outcomes. Current biomarkers for neuroendocrine tumors including chromogranin A, synaptophysin, Ki-67, somatostatin receptors, mammalian target of rapamycin, vascular endothelial growth factor and its receptor, and O 6-methylguanine-DNA methyl transferase are important in diagnosis and treatment of NETs. We report a rare case of multifocal primary hepatic neuroendocrine tumor (WHO grade 2) in a 79-year-old male. Due to tumor progression under octreotide therapy and the risk of rupture, a multimodal therapeutic approach was implemented. This included initial transcatheter arterial chemoembolization, followed by left lateral hepatectomy and wedge resection combined with intraoperative radiofrequency ablation. Surgical specimens were analyzed for CDK5 and p35 expression. The patient recovered well without complications and was discharged on postoperative day 9. In this case, cyclin-dependent kinase 5 (CDK5) and its activator, p35, were identified as potential novel biomarkers in NET. The differential expression of CDK5 and p35 observed in tumors of varying sizes suggests a correlation with tumor progression. These findings highlight the potential of the CDK5/p35 pathway as a therapeutic target for the management of advanced or metastatic NET.

Although stimulation of erythropoietin receptor (EPOR) signaling demonstrates cytoprotective effects-including anti-apoptosis, pro-proliferation, and promotion of inflammation resolution-in various disease models, its alterations and specific role in the process of pulmonary fibrosis are still not well understood. The study aimed at investigating the changes of lung EPOR signal in pulmonary fibrosis and the effect of different cell EPOR signal on pulmonary fibrosis. In a bleomycin-induced C57BL/6J mice model, fibrosis was assessed via Hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and hydroxyproline content. EPOR expression was measured in lung tissue and specific cells. Conditioned media (CM) from BLM/EPO-treated MLE-12, PMs, and C166 cells were applied to 3T3 fibroblasts, which were also treated with TGF-&#x3b2;1/EPO. Fibroblast activation was evaluated by &#x3b1;-SMA and Col-1 expression using RT-qPCR. Macrophage-specific (M&#x3a6;-EPORcko) and type II alveolar epithelial cell-specific (Sftpc-EPORcko) knockout mice were used to assess fibrosis severity. Lung overall EPOR expression decreased after fibrosis. Type II alveolar epithelial cells and macrophages showed the highest baseline EPOR expression, which declined post-fibrosis. CM from BLM+EPO-treated MLE-12 cells inhibited fibroblast activation, while media from PMs and C166 cells promoted it. Direct EPOR activation in fibroblasts enhanced their activation. M&#x3a6;-EPORcko mice exhibited attenuated fibrosis, whereas Sftpc-EPORcko mice displayed exacerbated fibrosis. EPOR signaling in macrophages and type II alveolar epithelial cells exerts opposing effects on pulmonary fibrosis, with targeted activation EPOR signaling in alveolar epithelial cells representing a potential therapeutic strategy.