Self-healed hydrogel containing carboxymethylated yeast β-(1→3)-glucan accelerates diabetic wound healing through pro-angiogenic, anti-inflammatory, and immunomodulatory

A meta-analysis of photodynamic therapy in the treatment of cervical intraepithelial neoplasia: Based on randomized controlled trials.

This study was to determine the frequency of HPV-hr and describe the distribution by categories (HPV16, HPV18, HPV-hr non16/18) among unvaccinated asymptomatic women in Peru over a 6-year period (2013-2018). In addition, the disease clearance rate is assessed in a percentage of cases. Of the 6,665 samples, 2,240 (33.6%) tested positive for HPV. Among the positive cases, single-genotype infections were caused by HPV-16 (14.8%), followed by HPV-18 (2.2%) and clustered high-risk HPV (HR-HPV) genotypes (66.7%). Multiple HPV-16 infections were more common than HPV-18 infections. In addition, 22 cases (1%) presented with infection with HPV-16, HPV-18, and HR-HPV genotypes. A subset of 116 samples from patients with 1 to 2 years of follow-up was analyzed further. Clearance rates were high, at 68.8% for HPV-16 infections and 67.5% for HR-HPV infections. However, the elimination rate of multiple infections with HPV-16 and HR-HPV genotypes was slightly lower, at 55.6%.

Airway mucus clearance from the lungs occurs by 2 widely recognized mechanisms: cilia-mediated clearance and high-velocity airflow-mediated cough clearance. However, a potentially important third mechanism of mucus clearance, referred to as cilia-independent gas–liquid transport (GLT), was proposed based on in vitro model systems to occur during normal tidal breathing but has largely been overlooked. We conducted in vitro and in vivo studies to investigate the role of tidal breathing airflow rates in mucus clearance. An in vitro airway culture bead-tracking model demonstrated airflow-dependent mucus transport at tidal breathing flow rates. As with other modes of mucus clearance, GLT was critically dependent on mucus concentration. In vivo studies in cilial beat-deficient mice demonstrated that GLT-mediated mucus clearance occurs during tidal breathing in the absence of cough, and the rate of GLT mucus clearance was dependent on breathing frequency and body orientation. These studies demonstrated that GLT is a third mechanism of mucus clearance and likely represents a significant mode of clearance in persons with cilial dysfunction. These findings indicate that increasing breathing rates through exercise, using mucus rehydrating agents or mucolytics, or combining these approaches may restore clinically and physiologically meaningful airway clearance in these patients.

To investigate the clinical utility of minimally invasive laparoscopic choledocholithotomy via the cystic duct confluence approach for secondary stones in slender common bile ducts. Data from 182 patients (74 male, 108 female; median age 45 years, range 32–68) with gallbladder calculus and secondary stones in slender common bile ducts (6–8 mm diameter), treated at Longhua District People’s Hospital, Guangdong, China from September 2021 to June 2024, were retrospectively analyzed. Of these, 90 underwent laparoscopic choledocholithotomy via cystic duct confluence with primary sutures (minimally invasive group), while 92 underwent laparoscopic common bile duct exploration with T-tube drainage (T-tube group). Clinical data and perioperative indicators were compared between groups. In carefully selected patients with secondary stones in slender common bile ducts, the laparoscopic minimally invasive choledocholithotomy via the cystic duct confluence approach is a favorable option, enabling rapid recovery and meriting broader application. Clinical data for the 2 groups were comparable (P > .05). The minimally invasive group had a mean operative duration of 95.67 ± 25.56 minutes, intraoperative hemorrhage of 10.0 mL (5.0–10.0 mL), and Winslow’s foramen drainage tube indwelling time of 4.47 ± 1.25 days. The stone clearance rate in the minimally invasive group was 100% (90 out of 90 patients). The T-tube group had an operative duration of 103.87 ± 29.83 minutes, intraoperative hemorrhage of 10.0 mL (5.0–10.0 mL), and Winslow’s foramen drainage tube indwelling time of 3.76 ± 1.06 days. The stone clearance rate in the T-tube group was 100% (92 out of 92 patients). There were no statistical differences between the groups (P > .05). Compared with the T-tube group, the minimally invasive group experienced significantly shorter postoperative hospital stay (7.72 ± 1.63 vs 12 ± 2.45 days), lower treatment costs (1.75 ± 0.27 × 104 vs 2.16 ± 0.36 × 104 CNY), exhibited reduced postoperative numerical rating scale pain scores (1.56 ± 0.67 vs 4.13 ± 0.79), and earlier postoperative time to ambulation (8.34 ± 1.67 vs 15.56 ± 3.83 hours; P < .05). Both groups had comparable bile leakage rates (1.11% vs 1.08%; P > .05), with no cases of residual stones or biliary strictures.

Trophic exposure to environmentally relevant concentrations of nanoplastics induces slight modulation of the antioxidant system in the estuarine bivalve Scrobicularia plana.

Homocysteine (Hcy) is a sulfur-containing intermediate metabolite during methionine metabolism. Studies indicate that individuals with polycystic ovary syndrome (PCOS) have higher circulating Hcy levels relative to unaffected populations. Hyperhomocysteinemia (HHcy) has been implicated in multisystem cytotoxicity. This study was designed to evaluate the association between Hcy levels and embryo quality and pregnancy outcomes in PCOS patients undergoing assisted reproductive technologies (ART). Mechanistic insights were explored through in vitro assays and combined network pharmacology analyses. A total of 599 patients with PCOS who were undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) were retrospectively analyzed. Patients were stratified into three groups based on Hcy levels (low, intermediate, and high). Comparative analyses of clinical and laboratory parameters were performed across strata. Multivariable logistic regression models were developed to evaluate the independent association between Hcy levels and reproductive outcomes after adjustment for potential confounders. In vitro assays were conducted using KGN cells, a human granulosa-like tumor-derived cell line. Cellular viability after exposure to graded concentrations of Hcy was quantified using the Cell Counting Kit-8 (CCK-8) assay, while cell apoptosis was observed via flow cytometry. For systems-level analysis, Hcy-associated targets were retrieved from SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. PCOS-related targets were curated from OMIM, GeneCards, DrugBank, and DisGeNET repositories. Overlapping targets were analyzed for protein-protein interaction (PPI) network construction using the STRING platform, followed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Comparative univariate analysis showed a significant difference in the high-quality embryos among the three Hcy strata, whereas other clinical parameters did not reach statistical significance. Multivariable regression analysis identified a robust inverse association between Hcy level and high-quality embryo rate (β = -1.04, 95% CI: -1.36 to -0.72; p < 0.0001), which remained stable after adjustment for confounding variables, including creatinine clearance rate (β = -1.06, 95% CI: -1.40 to -0.72; p < 0.0001). In vitro results showed that exposure to Hcy (80-160 µM, 24h) significantly reduced KGN cell viability and increased apoptotic rates in a concentration-dependent manner. Network pharmacology analysis identified 102 intersecting targets that may mediate Hcy-associated effects in PCOS. KEGG pathway enrichment revealed significant involvement in lipid metabolism and atherosclerosis, viral infections (i.e., hepatitis B and cytomegalovirus), the AGE-RAGE signaling pathways in diabetic complications, and the TNF signaling cascade. Higher Hcy levels were inversely correlated with high-quality embryo formation in PCOS patients, with each increase in Hcy associated with a measurable decline (1.4%) in embryo quality. Experimental validation indicated that Hcy exerts cytotoxic and pro-apoptotic effects on KGN cells. Combined network pharmacology further suggested that Hcy may influence PCOS. These results support a contributory role of HHcy in impaired PCOS and provide a preliminary mechanistic understanding for future investigation.

Effective clearance of high-risk human papillomavirus (HR-HPV) and disease remission are critical in managing cervical lesions. This study compared Nocardia rubra cell wall skeleton (Nr-CWS) versus 5-aminolevulinic acid photodynamic therapy for HR-HPV clearance and lesion regression. In this single-center retrospective cohort (June 2020–May 2023), 234 patients with HR-HPV infection were assessed. After 1:1 propensity matching, 144 patients remained (72 per group). Primary and secondary endpoints were HR-HPV clearance and disease remission rates, respectively. Baseline differences in thinprep cytologic test results persisted post-matching. Nr-CWS demonstrated superior HR-HPV clearance at 6 months (76.4% vs 48.6%; P < .001) and 1 year (87.5% vs 66.7%; P = .03). Disease remission rates showed no significant differences at 6 months (72.9% vs 85.5%; P = .10) or 1 year (78.0% vs 90.9%; P = .058). Nr-CWS significantly outperformed 5-aminolevulinic acid photodynamic therapy in achieving HR-HPV clearance, while both therapies showed comparable efficacy in disease remission.

To evaluate the early outcomes of total laparoscopic Kasai portoenterostomy (TL-KPE) for Type III biliary atresia (BA). A retrospective analysis included 45 pediatric patients with Type III BA who underwent Kasai portoenterostomy between January 2018 and December 2024. Patients were divided into three groups (n = 15 each): open KPE (O-KPE), conventional laparoscopic KPE (L-KPE, with extracorporeal intestinal anastomosis), and TL-KPE (with fully intracorporeal anastomosis). Comparative parameters included operative time, intraoperative blood loss, postoperative recovery metrics, incidence of cholangitis within 6 months, jaundice clearance, and native liver survival rates. Compared with the O-KPE group, the TL-KPE group showed significantly less intraoperative blood loss (P = 0.016). Compared with both the O-KPE and L-KPE groups, the TL-KPE group had markedly shorter time to bowel recovery and postoperative fasting time (all P < 0.001). Postoperative hospital stay was also significantly shorter in the TL-KPE group compared to the O-KPE (P = 0.016) and L-KPE (P = 0.034) groups. There were no significant differences among the three groups in operative time (P = 0.052), incidence of postoperative complications (P = 0.132), jaundice clearance cases (P = 0.278), early cholangitis (P = 0.932), or recurrent cholangitis (P = 1.000). No perioperative deaths occurred in any group. TL-KPE is a safe and technically feasible approach for Type III BA that enhances short-term postoperative recovery. These early results warrant further multicenter prospective studies with longer follow-up to evaluate potential long-term benefits on native liver survival.

Retrograde Intrarenal Surgery (RIRS) is prevalent in the treatment of renal calculi. The effect of Body Mass Index (BMI) on stone clearance and surgical results has not yet been investigated extensively. This study sought to analyze the effect of BMI on clinical, procedural, and postoperative outcomes of patients undergoing RIRS. This retrospective observational study was performed at the Pakistan Kidney and Liver Institute and Research Center (PKLI & RC), Lahore, between September 2018 and August 2024. Two hundred and sixty adult patients who underwent RIRS for renal stones were classified into four groups based on BMI: normal weight (<25 kg/m2), overweight (25-29.9 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (⩾40 kg/m2). The clinical and operative information was recorded from electronic data. Outcomes assessed included stone clearance, rates of complications, hospital stay, pain scores, and secondary intervention requirement. Statistics used were Chi-square tests, ANOVA/Kruskal-Wallis tests, and binary logistic regression. Stone clearance rates varied across BMI groups (p = 0.027), though multivariate analysis showed that BMI was not an independent predictor. Increased BMI was also found to be linked with more residual fragments (p = 0.029), longer hospital stays (p = 0.004), increased pain scores (p = 0.002). These differences, notwithstanding intraoperative safety, were uniform across the groups. Binary logistic regression found that stone burden ⩾20 mm was the only independent predictor of incomplete clearance (OR = 0.165, p < 0.001), whereas BMI was not an independent predictor. RIRS is a safe and successful procedure in all BMI groups. Obese and overweight patients can have suboptimal results, especially regarding clearance of stones and postoperative recovery. Burden of stone continues to be the most important predictor of surgical success. The results indicate the necessity of personalized planning and follow-up, particularly in those with high stone burden or higher BMI.

Molluscum contagiosum (MC) is a viral skin infection that poses significant physical and psychosocial burdens, particularly in pediatric and immunocompromised populations. Despite the availability of various treatment options, comparative efficacy and safety data remain limited. This systematic review, conducted in accordance with PRISMA guidelines, evaluates and compares the efficacy, safety, recurrence, and adverse effects of MC treatments. A total of 89 studies encompassing 12,955 participants were analyzed. Curettage, potassium hydroxide (KOH), autoinoculation, and podophyllotoxin demonstrated high clearance rates (97.8%, 73.8%, 79.4%, and 75.0%, respectively) with minimal local side effects. Cryotherapy and laser therapies offered rapid lesion resolution though laser treatment was associated with more discomfort and higher cost. Emerging therapies such as berdazimer gel demonstrated favorable safety profiles, particularly for pediatric patients, while intralesional immunotherapies like Candida and MMR vaccine showed encouraging results in patients with persistent or recurring lesions. The management of MC requires an individualized approach, balancing efficacy, safety, and patient-specific factors such as age, lesion severity, and immune status. Cantharidin, KOH, cryotherapy, autoinoculation, and podophyllotoxin offer high clearance rates, with immunotherapies and lasers offering additional options for resistant cases. Further standardized trials are needed to optimize treatment strategies and long-term recurrence.

Efficacy of low-dose rituximab as preemptive treatment of EBV DNA-emia after allogeneic hematopoietic stem cell transplantation.

Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant therapeutic challenge with high mortality rates. This study evaluated the clinical efficacy of high-dose ampicillin-sulbactam combined with colistin compared to standard colistin-based regimens. This retrospective study was conducted on 83 patients with CRAB-VAP at Hanoi Medical University Hospital, Vietnam, from May 2024 to May 2025. Patients were divided into an intervention group (n = 33) treated with high-dose ampicillin-sulbactam combined with colistin and a control group (n = 50) receiving other antibiotic regimens combined with colistin. Primary outcomes included 28-day mortality and total ventilation duration. The intervention group achieved significantly lower 28-day mortality (6.1% vs. 38.0%; p < 0.001) and higher microbiological clearance rates by day 14 (93.9% vs. 30.0%; p < 0.001). While early acute kidney injury was more frequent in the intervention group (66.7% vs. 24.0%), renal function outcomes were comparable by day 14. Multivariable analysis identified day-14 microbiological clearance as the strongest independent predictor of survival (hazard ratio [HR] = 13.03; p < 0.001). High-dose ampicillin-sulbactam combined with colistin significantly improves microbiological clearance and survival in patients with CRAB-VAP. Despite a higher incidence of transient nephrotoxicity, the regimen provides a substantial survival benefit.

Prostate-specific membrane antigen (PSMA)-targeting peptide-drug conjugates (PDCs) offer promise for the treatment of PSMA-positive prostate cancer, but their applications are limited by rapid clearance, poor pharmacokinetics, and low efficacy. Herein, we design a series of PDCs incorporating rational functional moieties, including a Glu-Ureido-Lys PSMA-targeting ligand, the cytotoxic payload monomethyl auristatin E (MMAE), and a cathepsin B-cleavable Val-Cit linker, combined with structural modifications such as free amine exposure, acetylation, stearic acid acylation, or p-iodophenylbutyric acid (PIBA) conjugation. Among them, the stearic acid-modified PSMA-targeting PDC (PDC-C18) is identified as a long-acting candidate for treating prostate cancer. PDC-C18 rapidly forms stable nanocomplexes with human serum albumin (HSA) through hydrophobic interactions, effectively shielding its hydrophobic moiety while preserving PSMA specificity. Notably, PDC-C18 exhibits a more than 160-fold extension in half-life compared to conventional PDCs, prolongs mean residence time (MRT) from 12.47 h to 23.93 h relative to PIBA-modified PDCs, and achieves a 60-fold reduction in clearance rate. This long-acting property translates into a remarkable tumor suppression rate of 96.91%, simultaneously avoiding the side effects associated with traditional PIBA modification strategies. Overall, this study presents an effective approach to improving the pharmacokinetic behavior of PDCs and provides valuable insights for the development of next-generation tumor-targeted therapies.

Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts.

Microplastics are pervasive environmental pollutants that pose potential risks to human health, particularly through inhalation. Despite growing concerns, limited data exist on how environmental aging, such as ultraviolet (UV) irradiation, affects the pulmonary toxicity of inhaled nano- and microplastics. This study evaluated the influence of UV-driven surface oxidation on the inflammatory potential and lung clearance kinetics of polystyrene (PS) particles. Spherical PS particles (50, 200, and 400nm) were synthesized, selectively oxidized by UV irradiation, and thoroughly characterized for surface chemistry and intrinsic reactive oxygen species (ROS) generation. Mice exposed to these particles via pharyngeal aspiration (75µg/mouse; n = 4 per group) exhibited significantly greater acute pulmonary inflammation from UV-oxidized particles compared to pristine particles, with smaller ones (50nm) displaying slightly higher inflammogenicity. Although inflammation largely resolved by four weeks post-exposure (75µg/mouse; n = 4 per group), mild neutrophilic inflammation persisted. Notably, particle-induced ROS generation and subsequent cellular oxidative stress in alveolar macrophages showed strong correlations with acute inflammatory endpoints. Additionally, the particle dispersion method significantly affected lung clearance rates: particles dispersed in distilled water (DW) containing 10% ethanol exhibited shorter clearance half-lives (3-8 days) than those dispersed in 5% mouse serum (~ 18 days) (75µg/mouse; n = 4 per group). These results highlight the dispersion medium as an important experimental variable influencing pulmonary clearance and toxicity interpretation. These findings suggest that the surface oxidation of nano- and microplastics through environmental aging can increase associated health risks. However, within the tested size range (50-400nm), neither surface oxidation nor particle size markedly altered the overall lung clearance pattern.

Abstract Objective This study evaluates the impact of acoustic gunshot detection technology (ShotSpotter) on crime rates, emergency call volume, police response times, and case clearance rates in Detroit, Michigan. Methods We employ a difference-in-differences design leveraging the staggered rollout of ShotSpotter across Detroit neighborhoods. The treatment group consists of several areas receiving coverage in March 2021, while the control group is comprised of areas covered by ShotSpotter starting in October 2022. Using Detroit Police Department data from January 2017 to October 2022, we estimate Poisson regression models for crime and call volume outcomes and log-linear regression models for police travel times. All models include area and time fixed effects, with robust standard errors. Results ShotSpotter installation is associated with a 6.5% reduction in violent crime ( p &lt;0.10) but a 8.5% increase in nonviolent crime ( p &lt;0.1). The technology produces a 322% increase in gunshot-related calls for service and a 10.4% decrease in total non-gunshot Priority 1 calls. There was no significant different in police travel time. We find no significant change in case clearance rates for any crime category. Conclusion While gunshot detection technology reduces violent crime in Detroit, it imposes substantial operational costs through increased call volume and slower response to technology-generated alerts. Municipalities must weigh public safety benefits against resource constraints when considering adoption. The heterogeneous effects across crime types and policing outcomes highlight the need for context-specific cost-benefit analysis.

Analysis of factors affecting lesion or HPV clearance rate after photodynamic therapy of persistent cervical intraepithelial neoplasia grade 1.

Therapeutic plasma exchange (TPE) is being increasingly utilized in the clinical management of severe rheumatic immune diseases, providing an effective means for rapidly removing pathogenic autoantibodies and inflammatory mediators. However, the non-selective nature of this technique can also lead to the unintended clearance of concomitantly administered antirheumatic drugs, potentially compromising therapeutic efficacy and disease control. Therefore, effective management of potential drug removal process during TPE and the implementation of individualized risk assessment are crucial for optimizing treatment outcomes in patients undergoing TPE. The variability in the extent of drug removal during TPE is primarily determined by their distinct pharmacokinetic characteristics, necessitating the establishment of a systematic, evidence-based strategy for adjusting drug administration regimens in patients receiving TPE treatment. This review synthesizes current evidence from 65 studies on the removal of antirheumatic drugs during TPE, identifying key determinants influencing clearance rates, including volume of distribution, protein binding, molecular size, and elimination half-life. Our analysis reveals that the risk of drug removal exists as a continuous spectrum: large monoclonal antibodies (e.g., rituximab, natalizumab), characterized by a large molecule size, low volume of distribution, with which mostly confined to the vascular space, are cleared with high efficiency. This finding supports the clinical recommendation of administering such drugs after TPE. For drugs with limited direct evidence, we propose a predictive model based on fundamental pharmacokinetic parameters to estimate their removal risk and guide clinical decision-making. Based on this evidence, we have constructed a stratified clinical management framework. It aims to maintain effective therapeutic drug exposure levels during chronic TPE therapy and to provide a rationale for the judicious application of TPE in overdose scenarios. Implementing this pharmacokinetic-informed, risk-adapted individualized strategy is important for ensuring treatment continuity, enhancing patient safety, and advancing empiricism-based therapy towards precision medicine.

Optimized intracerebral hematoma management with ultrasound-guided minimally invasive surgery (HUG-MIS): A technical note.