Bladder cancer (BC) is the 10th most common cancer worldwide, accounting for approximately 5% of new cases. Several factors contribute to tumor progression, including increased MMP9. Recently, CRISPR-Cas9 and immunotherapy have offered high specificity for treatments; therefore, we edited MMP9 using CRISPR-Cas9 methodology to inhibit metastatic mechanisms and evaluated potential synergy with BCG and anti-PD-L1 therapy. We performed CRISPR-Cas9 gene editing using an RNP complex in the MB49 murine BC cell line. Gene expression of MMPs, integrins, and BAX was analyzed, along with protein expression. Cells were divided into a Scramble control group and CRISPR-Cas9 for the MMP9 edited group (MMP9-/-). Female C57BL/6 mice received orthotopic BC cells (scramble and MMP9-/- groups) treated with BCG and anti-PD-L1. Statistical analyses were performed using t test or ANOVA. MMP9 gene and protein expression were reduced in the MMP9-/- group compared with the scramble group. No differences were observed in other MMPs. Decreased ITGB3, increased BAX gene expression, as well as reduced migration and adhesion to ECM were observed in the MMP9-/- group. Animals in the scramble group showed greater weight loss and lower survival than treated groups. Overall, MMP9 modulated key cellular mechanisms, but did not show synergistic effects with BCG and anti-PD-L1 in vivo.

Oncological surgery is undergoing profound transformation driven by advances in systemic therapy, immunotherapy, and minimally invasive techniques. This narrative review examines whether open abdominal surgery retains clinical relevance in gynecological malignancies or has been superseded by modern alternatives.

A literature search was conducted in PubMed combining terms related to gynecological malignancies, abdominal surgical procedures (open, laparoscopic, robotic, cytoreduction, pelvic exenteration), and personalized systemic therapies. Original articles, reviews, and guidelines in German and English were included. Two independent reviewers screened titles, abstracts, and full texts, extracting data on study design, interventions, and clinical endpoints (R0 resection, morbidity, progression-free and overall survival).

For cervical cancer, open radical abdominal hysterectomy as the standard of care was internationally confirmed. In endometrial cancer, minimally invasive approaches are established for early-stage disease, while laparotomy remains the gold standard in advanced stages requiring cytoreductive surgery. For ovarian, tubal, and primary peritoneal carcinoma, open cytoreductive surgery with the goal of macroscopically complete resection remains guideline recommended. Emerging biomarkers such as circulating tumor DNA may further refine patient selection and surgical decision-making.

Open abdominal surgery remains indispensable in gynecological oncology. Rather than being replaced, it is evolving into a specialized, biology-adapted component of multimodal treatment strategies. Surgical indications are becoming less frequent but more complex and individualized. Patient selection in experienced centers remains the decisive factor.

Indications for repeat biopsy after an initial negative prostate biopsy remain poorly defined. Therefore, this study aimed to investigate the effectiveness of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system as a guide for repeat biopsy.

We retrospectively reviewed patients who underwent repeat prostate biopsy and had bpMRI performed before both biopsies between 2013 and 2024. The association of clinically significant prostate cancer (csPCa) detection with initial Prostate Imaging Reporting and Data System (PI-RADS) and PRECISE scores was analyzed. The predictive effects of prostate-specific antigen density before repeat biopsy (re-PSAD) and PSA velocity (PSAV) on csPCa were assessed in patients progressing to or maintaining re-PI-RADS 3.

104 individuals were included with a median follow-up period of 28.58 months and a PSAV of 0.90 ng/mL/year (interquartile range (IQR), -0.17 to 2.57 ng/mL/year). The csPCa detection rate at repeat biopsy was 24.0%. 42 participants (40.4%) had PRECISE scores of 4-5, 43 (41.3%) had scores of 3, and 19 (18.3%) had scores of 1-2. A higher PRECISE score corresponds to a higher csPCa detection rate, with csPCa diagnosed in 52.4% of patients with PRECISE scores of 4-5. In subgroup analyses, re-PSAD and PSAV avoided 65.4% and 53.8% of repeat biopsies, respectively, and would have caused 5.9% and 0.00% of missed csPCa.

PRECISE may be useful for guiding repeat biopsy decisions and may provide incremental value for predicting csPCa when interpreted together with PI-RADS. Additionally, PSAD and PSAV can assist in screening for repeat biopsy.

Question Indications for repeat prostate biopsy after an initial negative result remain poorly defined. Can sequential MRI PRECISE scoring help inform repeat biopsy decisions? Findings In our retrospective cohort, PRECISE 1-2 yielded no clinically significant cancer, while PRECISE 4-5 showed a 52.4% detection rate. PSA parameters aided equivocal cases. Critical relevance statement This study evaluates sequential MRI PRECISE scoring, suggesting its potential to help reduce unnecessary repeat biopsies for regressing lesions while identifying high-risk progressing abnormalities.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide and effective therapeutic targets remain limited.

This study aimed to investigate the expression and functional role of miR-326 in gastric cancer, identify its direct target gene and elucidate the underlying molecular mechanisms involving the PI3K/Akt signaling pathway and the regulation of inflammatory cytokines.

miR-326 expression was detected by qRT-PCR in 56 paired GC tissues and adjacent normal tissues, as well as in GC cell lines (SGC-7901, MKN-45, AGS) and normal GES-1 cells. CCK-8 assays, flow cytometry, Transwell migration/invasion assays and ELISA were performed to assess cell proliferation, apoptosis, migration/invasion and cytokine secretion. Dual-luciferase reporter assay and Western blotting were used to validate the target gene and pathway activation.

miR-326 was significantly upregulated in GC tissues and cell lines. ETS1 was identified as a direct target of miR-326. Overexpression of miR-326 reduced ETS1 expression, activated the PI3K/Akt pathway (increased p-PI3K and p-AKT), promoted cell proliferation, migration and invasion, inhibited apoptosis and induced an imbalance of inflammatory cytokines (increased IL-6 and TNF-α; decreased IL-10 and IL-17). Co-overexpression of ETS1 or treatment with the PI3K inhibitor LY294002 reversed these effects.

miR-326 promotes malignant phenotypes in gastric cancer cells by targeting ETS1, activating the PI3K/Akt signaling pathway, and inducing dysregulation of inflammatory cytokines. The miR-326/ETS1/PI3K/Akt axis may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.

Estrogen can promote aggressive tumor phenotypes in estrogen receptor-positive (ER+) breast cancer; however, ER- cell lines are not widely considered estrogen responsive. Noncanonical estrogen-stimulated pathways such as the membrane-bound G protein-coupled estrogen receptor (GPR30) can mediate migratory and proliferative phenotypes in breast cancer and are postulated to promote resistance to aromatase therapies. Moreover, dysregulation of UDP-glucose 6-dehydrogenase (UGDH), a ubiquitously expressed enzyme critical to the metabolism of UDP-glucuronic acid into extracellular matrix precursors and hormone regulation, is associated with tumorigenesis. Here, we illustrated the impact of estrogen stimulation on tumor phenotypes in ER+ and ER- cell models in vitro and in vivo. We then demonstrated UGDH's association with metastatic breast cancer via single-cell sequencing of patient specimens. Genetic knockdown of UGDH blunted estrogen-stimulated tumor phenotypes in vitro, ex vivo, and in vivo using both ER+ and ER- breast cancer lines. Finally, we demonstrated that UGDH knockdown blunted noncanonical estrogen stimulation through GPR30. Ultimately, our study validated prior studies demonstrating estrogen-responsive malignant phenotypes in ER- breast cancer and demonstrated that estrogen-stimulated breast cancer progression can be mediated through noncanonical pathways (e.g., UGDH/GPR30), regardless of ER status.

We evaluated the effects of a 24-h istaroxime infusion on changes in self-reported dyspnea among patients with acute heart failure (AHF).

Patients hospitalized for AHF with ejection fraction ≤40 were randomized to receive a 24-h infusion of placebo or istaroxime at doses of 0.5 (Ista-0.5) or 1.0 μg/kg/min (Ista-1.0). Self-reported dyspnea was assessed by means of a visual analogue scale (VAS). Dyspnea VAS area under the curve (AUC) and changes in VAS dyspnea from baseline through 24 and 48 h were compared between istaroxime- and placebo-treated patients.

Among 113 AHF patients (n = 39 placebo, n = 39 Ista-0.5, n = 35 Ista-1.0), a statistically significant difference in dyspnea VAS AUC from baseline through 24 h was observed in the pooled istaroxime arm vs. the placebo arm [win odds 1.44, 95% confidence interval (CI) 1.00 to 2.07; P = 0.048], with similar findings for Ista-0.5 vs. placebo (win odds 1.48, 95% CI 1.01 to 2.18; P = 0.047). Win odds consistently favored istaroxime through 48 h, though significance was not maintained. Results were numerically more pronounced among patients with baseline dyspnea VAS < 80, particularly for Ista-0.5 vs. placebo (win odds 1.71, 95% CI 0.76 to 3.83; P = 0.172). Consistent findings were observed changes in dyspnea VAS through 24 h, with a least square mean difference of 2.6 points (95% CI -1.8 to 7.0) between Ista-1.0 and placebo.

Among patients with AHF, 24-h istaroxime infusion was associated with a significantly higher probability of dyspnea improvement compared with placebo through 24 h, with results being numerically more pronounced among patients with worse dyspnea at baseline.

The post‑acute sequelae of SARS‑CoV‑2 infection (PASC, "Long COVID") remain difficult to evaluate because standardized diagnostic tools are limited. We applied the recently proposed PASC index (score ≥ 12) to describe the 12‑month trajectory of Long COVID symptoms.

In this prospective cohort, adults with laboratory‑confirmed COVID‑19 were consecutively enrolled from November 2022 to February 2025. Long COVID was defined by a PASC index of ≥12 across 12 symptom domains persisting for at least 30 days post-infection. Symptom questionnaires were completed at 1, 3, 6 and 12 months after infection.

Among 183 participants, 48 (26.2%) met Long COVID criteria. Symptom assessments indicated that the proportion of participants meeting the Long COVID threshold declined from 27% at 1 month to 18% at 12 months, although this change was not statistically significant (p = 0.16). Participants classified as having Long COVID had consistently higher PASC index values across follow-up, while pairwise within-person comparisons showed no significant temporal changes in either the Long COVID or non-Long COVID group. These findings suggest that the overall symptom burden remained relatively stable over time, despite fluctuations in threshold status.

During 12 months of follow-up, approximately one quarter of participants met the PASC index threshold at least once. Among participants with repeated assessments, PASC index scores showed limited within-person change, although differential non-response limits the interpretation of temporal prevalence estimates.

Chronic lung diseases (CLDs) pose a significant public health challenge globally, particularly among aging populations. Physical activity (PA) is a modifiable lifestyle factor with potential benefits for respiratory health. This study aimed to investigate the association between PA levels and the odds of CLDs among middle-aged and older adults in China.

Data were derived from the 2020 China Health and Retirement Longitudinal Study (CHARLS). A total of 8,143 participants aged 45 years and older were included. Multivariable logistic regression and subgroup analyses were performed to examine the association between PA and CLDs.

The overall prevalence of CLDs was 18.11% (1,475/8,143). In the multivariable model, high-intensity physical activity was associated with lower odds of CLDs compared to low-intensity activity (OR=0.86, 95% CI: 0.74-0.99, P = 0.039), while moderate-intensity activity showed a trend but was not significant (OR=0.87, 95% CI: 0.74-1.02, P = 0.085). Subgroup analyses revealed a significant interaction by sex and age (P for interaction <0.05). The inverse association was significant among males (moderate: OR=0.75; high: OR=0.74) and among participants aged ≥65 years (high-intensity: OR=0.80, 95% CI: 0.68-0.94, P = 0.008), but not among females.

This cross-sectional analysis found that high-intensity physical activity was independently associated with lower odds of CLDs in Chinese adults aged 45 and older, with the association varying by age and sex. Promoting regular physical activity, particularly in older adults and middle-aged men, may be a valuable public health strategy for respiratory health in China's aging population. Further longitudinal studies are needed to confirm these findings.

BACKGROUND Loss of smell can impair quality of life. Olfactory disorders are often caused by viral infections, including SARS-CoV-2. The aim of the study was to evaluate the effectiveness of a structured, multidisciplinary rehabilitation program, including pharmacological treatment and speech therapy-guided olfactory training, in patients with post-COVID olfactory disorders. MATERIAL AND METHODS A total of 75 patients (15 men, 60 women) were allocated to a study group (n=50) or control group (n=25) using a systematic assignment method. Both groups received the same pharmacological treatment (intranasal corticosteroids and topical vitamin A), saline nasal irrigation, and elements of speech therapy-guided olfactory training. In addition, the study group performed classical olfactory training using 4 odorants twice daily. Olfactory function was assessed using the Sniffin' Sticks Test (SST). RESULTS For the total SST score, the mean change before and after intervention in the study group was 7.9 points (P<0.001). In the control group, the mean change was 2.8 points (P=0.006). CONCLUSIONS Classical olfactory training was associated with greater improvement in post-COVID olfactory disorders compared with pharmacological treatment supplemented with speech therapy-guided olfactory training alone. The observed effects may be related to the combined use of intranasal corticosteroids, topical vitamin A, and saline nasal irrigation; however, the individual contribution of these interventions cannot be determined. The potential contribution of a multidisciplinary approach involving a physician, speech therapist, and psychologist remains to be established.

Early alterations in pulmonary microstructure are central to the onset and progression of chronic obstructive pulmonary disease (COPD) and acute lung injury, yet these changes remain undetectable with conventional attenuation-based computed tomography (CT). Dark-field computed tomography is sensitive to small-angle x-ray scattering generated by intact alveolar structures; however, all prior in vivo studies have been cross-sectional and pseudo-longitudinal, precluding direct observation of disease evolution within the same subject. A longitudinal, microstructure-resolved imaging approach is needed to capture true disease trajectories, reduce inter-subject variability, and support preclinical therapeutic development.

We developed a dedicated dark-field CT imaging system and integrated workflow, including dose-optimized acquisition, a mouse-specific fixation device, motion compensation, pseudo-dark-field suppression, and deep learning-based three-dimensional lung segmentation, to support repeated imaging over 12 weeks in healthy, inflammatory-injury, and COPD mouse models.

The dark-field coefficient (µ_d) showed distinct, model-specific temporal trajectories and appeared to reflect microstructural changes when attenuation (μ) remained stable. It exhibited pronounced left-right heterogeneity in the inflammatory-injury model and markedly different trajectories between two COPD mice under an identical protocol, underscoring inter-subject variability that the within-subject design captured. Overall, µ_d changed earlier than μ, and findings were consistent with terminal histology.

Our results suggest the feasibility of long-term in vivo dark-field CT in preclinical lung studies. The dark-field coefficient shows promise as a potential noninvasive biomarker for early pulmonary damage, quantitative disease assessment, and therapy monitoring, supporting further investigation of longitudinal dark-field imaging in lung pathology and drug development.

Question First laboratory-based longitudinal in vivo dark-field CT in mouse lung disease models over 12 weeks. Findings Dark-field signal showed more pronounced temporal variation than attenuation signal, with distinct model-specific trajectories. Relevance statement These findings establish a methodological foundation for longitudinal preclinical imaging of lung microstructure, which may support future translational research and the development of time-resolved imaging strategies for pulmonary disease.