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The International Prognostic Index (IPI) and IPI related prognostic indexes are widely used for risk-stratification in lymphoma. However, identifying poor prognostic group patients remains a significant objective. This study aimed to develop a predictive prognostic model for DLBCL treated with R-CHOP immunochemotherapy. A cohort comprising 167 individuals newly diagnosed with DLBCL between January 2016 and June 2021 at Jiangsu cancer hospital, Nanjing Medical University were enrolled for investigation. Univariate and multivariate Cox analysis were used for variable selection. The Akaike information criterion (AIC) guided the selection of factors for constructing the nomograms, along with a novel prognostic index for assessing both progression-free survival (PFS) and overall survival (OS). Internal validation was performed with the bootstrap method(B = 1000). Age, Lactate dehydrogenase (LDH), stage, extra-nodal sites and absolute CD4 + T cell counts (ACD4C) were associated with both PFS and OS. These discerned prognostic factors were subsequently employed in constructing nomograms for PFS and OS, respectively. The C-indexes of Internal validation performed with the Bootstrap method were 0.76 (PFS: 95%CI 0.67-0.80),0.81(OS:95%CI 0.72-0.85), respectively. The calibration plots, alongside internal bootstrap resampling, demonstrated commendable consistency between predictions and observations. For enhanced clinical applicability, we devised a novel immune prognostic index, categorizing DLBCL patients into four distinct risk groups: low, low-intermediate, high-intermediate, and high risk, corresponding to 0, 1-2, 3, 4-5 risk factors respectively. Kaplan-Meier analysis underscored the superior discriminatory capacity of the immune index in assessing the prognosis across various risk groups. The proposed immune index is a useful tool to predict the prognosis of DLBCL patients treated with R-CHOP immunochemotherapy in this study.

This study aimed to develop and evaluate a deep learning-based surgical navigation system capable of recognizing the ureter, uterine artery, and bladder-uterine dissection plane during minimally invasive gynecologic surgery. An artificial intelligence (AI) model was developed at the University of Tokyo Hospital using videos of prior surgeries. Surgical videos of 27 laparoscopic or robot-assisted total hysterectomies were used to create training and validation datasets, with an additional set of cases serving as an independent test set. Key frames were manually annotated to train segmentation models for the ureter and uterine artery. A separate model visualized loose connective tissue fibers (LCTF) to aid in recognizing the bladder-uterine peritoneal dissection plane. Quantitative performance was assessed using standard segmentation metrics, and a qualitative evaluation was conducted by nine gynecologic surgeons using predefined scoring criteria. The segmentation models achieved moderate quantitative performance, with Dice similarity coefficients of approximately 0.51 for the ureter and 0.45 for the uterine artery. In contrast, qualitative evaluation demonstrated favorable clinical interpretability. The mean recognition scores assigned by nine expert surgeons were 4.12 for the ureter and 3.45 for the uterine artery on a five-point scale, indicating that most structures were recognized clearly with only minor misrecognition. For bladder dissection, visualization of connective tissue fibers enabled identification of the correct dissection plane in the majority of evaluated frames; more than 70-80% of connective tissue was recognizable in most frames, and substantial misrecognition was uncommon. This study demonstrates that a deep learning-based system can recognize three key elements of a total hysterectomy: the ureter, the uterine artery, and the bladder-uterine dissection plane. Despite modest quantitative metrics, qualitative assessments indicated strong clinical utility. These findings establish a foundation for an integrated AI-assisted surgical navigation platform to enhance the safety and standardization of minimally invasive gynecologic surgery.

Asymptomatic contralateral patent processus vaginalis (CPPV) is commonly detected during the laparoscopic repair of inguinal hernias in children and is a risk factor for metachronous contralateral inguinal hernias (MCIHs). However, predicting CPPV preoperatively is challenging, and evidence on its clinical predictors is limited, particularly regarding sex-specific differences. We aimed to identify preoperative predictors of CPPV and to evaluate sex-specific risk factors. This retrospective observational study was conducted at a single tertiary-care university hospital and included children (aged&#x2009;<&#x2009;16&#xa0;years) who underwent single-incision laparoscopic percutaneous extraperitoneal closure for a clinically unilateral inguinal hernia or hydrocele between 2013 and 2024. Those who underwent surgery for a recurrent inguinal hernia, MCIH, or bilateral presentation were excluded. The preoperative clinical characteristics were analyzed. Missing data were addressed using multiple imputation before conducting multivariable logistic regression analyses in the overall and sex-stratified cohorts to determine the independent predictors of CPPV. Overall, 1031 children (502 males, 529 females) were included. CPPV was identified in 511 (49.6%) patients. In the multivariable analysis of the overall cohort, left-sided presentation and history of incarceration were independently associated with CPPV, whereas sex was not. In sex-stratified analyses, hydrocele was independently associated with CPPV in males (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.06-2.45; P&#x2009;=&#x2009;0.03). In females, left-sided presentation (OR, 2.80; 95% CI, 1.94-4.03; P&#x2009;<&#x2009;0.001), incarceration history (OR, 5.19; 95% CI, 1.39-19.30; P&#x2009;=&#x2009;0.014), and older age (OR, 1.01; 95% CI, 1.00-1.01; P&#x2009;=&#x2009;0.046) were associated with CPPV. Preoperative predictors of CPPV showed sex-specific patterns. Sex was not an independent predictor; however, hydrocele was associated with CPPV in males, whereas, in females, left-sided presentation and incarceration history showed strong independent associations with CPPV. These findings may inform preoperative counseling, operative approach selection, and meticulous contralateral laparoscopic exploration, potentially reducing the risk of subsequent MCIH.

Cryptococcosis is a severe invasive fungal infection with limited therapeutic options beyond fluconazole-based regimens. Isavuconazole, a broad-spectrum triazole antifungal, has emerged as a potential alternative, although clinical data supporting its use remain scarce. We aimed to evaluate the real-world effectiveness and safety of isavuconazole in patients with different forms of cryptococcosis. A retrospective observational study was conducted at a tertiary-care hospital, including patients with cryptococcosis who received isavuconazole at any treatment phase. Standard microbiological methods were used for pathogen identification and susceptibility testing. Demographic, clinical, and microbiological data were collected. Clinical and microbiological responses and tolerability were assessed at end of treatment or until death. Eight patients with cryptococcosis received isavuconazole, most of whom were immunocompromised. Clinical presentations included pulmonary and disseminated disease, with Cryptococcus neoformans as the predominant species. Isavuconazole was primarily used during the consolidation and maintenance phases, after induction therapy with amphotericin B and flucytosine for 2&#xa0;weeks in most cases, and as salvage therapy in two patients. It was well tolerated during prolonged treatment (6-12&#xa0;months). In the two patients with isavuconazole therapeutic drug monitoring, plasma total trough concentrations were within the therapeutic range (5 and 3.5&#xa0;&#xb5;g/mL, respectively), whereas cerebrospinal fluid total concentration levels were undetectable. A favorable clinical response was observed in four patients, while three remain on treatment with ongoing clinical improvement; one patient died early. Microbiological clearance was achieved in all culture-positive cases. Isavuconazole demonstrated clinical effectiveness in this cohort of patients across different presentations of cryptococcosis. Treatment was safe and well tolerated, supporting its role as an alternative antifungal option against Cryptococcus, particularly when fluconazole is limited by adverse effects or drug-drug interactions. However, data on central nervous system penetration were limited, and further studies are needed to better define its role in cryptococcal meningitis management.

Subsequent to an intracerebral hemorrhage (ICH), a cascade of neuroinflammatory response drives the process of secondary brain injury. At present, no anti-inflammatory nor neuroprotective pharmacological interventions have been demonstrated to improve functional outcome after ICH. This Phase 2b study was designed to establish the safety and feasibility of CN-105, a neuroprotective and anti-inflammatory pentapeptide designed from the receptor binding region of apolipoprotein E, in patients with acute primary supratentorial ICH. The Singapore CN-105 in Participants with Acute Supratentorial ICH Trial (S-CATCH, NCT03711903) was a randomized, double-blind, placebo-controlled trial involving 60 patients (30 CN-105, 30 placebo) treated within 12&#xa0;h of symptom onset. Safety was assessed through adverse events (AEs) and serious AEs (SAEs), while efficacy was evaluated using functional outcome measures, including the modified Rankin Scale (mRS) at 90&#xa0;days. CN-105 was safe and well tolerated in patients with acute ICH, with no significant differences in incidence of SAEs between groups (30% SAEs in placebo vs. 26.7% in CN-105). Notably, fewer patients treated with CN-105 group experienced in-hospital neurological deterioration (0 vs. 10% in placebo). While treatment was not associated with a statistically significant improvement in 90-day mRS, higher proportion of patients treated with CN-105 achieved favorable mRS scores (&#x2264;&#x2009;3) compared with those in the placebo group (77.8 vs. 66.7%; p&#x2009;=&#x2009;0.35). This Phase 2b trial confirmed the safety and feasibility of CN-105 administration in the acute setting of ICH. Although no statistically significant improvements in neurological outcomes were found, the observed trends warrant further investigation. Future Phase 3 trials should focus on refining patient selection and assessing the therapeutic efficacy of CN-105 in more targeted subgroups such as those with medium-sized subcortical ICH. Trial registration NCT03711903, https://clinicaltrials.gov/ https://clinicaltrials.gov/study/NCT03711903?term=NCT03711903&rank=1 . Registered 16 October 2018.

Breast density is a breast cancer risk factor. The accurate quantification of breast density requires reliable segmentation of dense tissue in mammograms, but it is a challenging task due to large variations in tissue appearance across hospitals and imaging devices. We propose MammoDenseSegNet, a new deep encoder-decoder convolutional neural network designed to enhance segmentation performance through two complementary modules: a) Adaptive dual attention module, which captures long-range spatial and channel interdependencies to provide focused attention on relevant dense tissue areas regardless of their location; and b) Multi kernel receptive field module, which enlarges the network's receptive field at the bottleneck layer to aggregate multi-scale contextual features. Additionally, a multi-scale dice loss with deep supervision guides learning across decoder levels to improve robustness. We evaluated MammoDenseSegNet on two public digital mammogram datasets (VinDR-Mammo and EMBED) and one private dataset, spanning a variety of breast densities and imaging artifacts in a total of 1499 images from 606 women. Statistical analysis was done using generalized linear models accounting for correlation among images from the same women and adjusting for potential confounders (proc genmod, proc mixed, SAS v.9.4, SAS Institute, Cary, NC). MammoDenseSegNet demonstrated consistently high performance across various conditions (with Recall ranging from 0.64 to 0.90 and Dice from 0.63 to 0.91) and significantly (p&#x2009;<&#x2009;0.001) outperformed the publicly available state-of-the-art algorithm based on the VGG16 (with Recall from 0.04 to 0.91 and Dice from 0.06 to 0.82 across the same conditions). The improvement was largest for low-density tissue, where the baseline algorithm practically fails (with the mean Recall of 0.14 and Dice of 0.16) while MammoDenseSegNet remained clinically useful (with the mean Recall of 0.66 and Dice of 0.63).

Although pelvic landmarks have traditionally been used to estimate the femoral head center (FC), their reliability may be limited in patients with developmental dysplasia of the hip (DDH). In contrast, femoral-based reference methods have been insufficiently investigated. This study aimed to evaluate the feasibility and clinical utility of estimating the FC location in DDH using a three-dimensional model derived from trochanteric landmarks. We retrospectively analyzed 128 femurs from 84 female patients with DDH (mean age, 36.9&#x2009;years) who underwent curved periacetabular osteotomy (CPO) from April 1, 2010, to September 30, 2020, and had no symptoms involving the spine or knee. The FC was estimated using multiple regression models based on the three-dimensional coordinates (x, y, and z) of the greater and lesser trochanter tips. Differences between the estimated and actual FC positions were assessed along all three axes. Correlation coefficients between the estimated and actual FC ranged from 0.725 to 0.875 across the three directions. The mean absolute error was 2-3&#x2009;mm, with greater errors observed in the anteroposterior direction than in the craniocaudal direction. An estimation error within 3&#x2009;mm may be considered relatively small in the context of clinically acceptable ranges reported in previous studies for restoring femoral offset and leg length during total hip arthroplasty (THA), supporting the practical applicability of this method in preoperative planning. The accuracy of the present approach was comparable to that reported in healthy populations and exceeded that of previous pelvic landmark-based regression techniques. This trochanter-based three-dimensional method enables clinically acceptable estimation of the FC in patients with DDH and may serve as a useful adjunct for planning of the femoral component when the native FC is difficult to identify.

Deep Brain Stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD), yet registry-based data from developing countries remain limited. This study reports the establishment and feasibility of the Iranian Deep Brain Stimulation Registry for Parkinson's Disease (IDBSR-PD). We conducted a single-center feasibility study at the Research Center for Neuromodulation and Pain, including all PD patients undergoing DBS implantation since 2014. Primary feasibility outcomes included patient enrollment coverage, follow-up adherence, data completeness, multidisciplinary implementation, and the sustainability of technical infrastructure. Secondary outcomes included descriptive patient characteristics. Only descriptive statistics were performed; no hypothesis testing or longitudinal outcome analyses were conducted. A total of 208 patients were enrolled (65.4% male; mean age 58.4&#x2009;&#xb1;&#x2009;10.2 years). Enrollment increased progressively over time, peaking in 2024 (n&#x2009;=&#x2009;41). Patients were referred from multiple provinces across Iran. Data validation mechanisms and regular surveillance ensured acceptable data completeness. The IDBSR-PD demonstrates the feasibility and sustainability of a web-based DBS registry in a developing country. These findings confirm the viability of structured data collection and provide a foundation for future multicenter and longitudinal outcome research.

Knee osteoarthritis (KOA) is a common degenerative bone disease, and transcutaneous electrical nerve stimulation (TENS) is an alternative and complementary therapy (ACM). This study revealed the role of TENS in regulating the intestinal microbiota in KOA rats. This study concentrated on the intestinal microbiota of KOA rats which were treated with TENS for 1, 2, and 3 weeks. Three intensities of TENS were used to treat KOA rats, and the expressions of IL6/8, PI3K-AKT were measured. The intestinal microbiota was analyzed by 16&#xa0;S rDNA sequencing. Compared with the Model Control group, TENS could improve symptoms of KOA rats and inhibit the expressions of IL6/8 by down-regulating the PI3K-AKT expression. After 3 weeks of treatment with TENS, compared with the Model Control group, the abundances of Bacteroidetes, Bacteroidetes, and Thermodesulfobacteria increased in the TENS groups; the abundances of Ficmicutes, Campylobacter, and Verruca decreased in the TENS groups. TENS could improve the histomorphology of knee and inhibit inflammation in KOA rats. After treatment with TENS, the intestinal microbiota gradually changed from 1,2,3 weeks and the abundance of them was different with three intensities of TENS. Further study will elucidate the underlying mechanisms of TENS in altering gut microbiota and the potential therapeutic applications of these intestinal microbiota for KOA.

Same-day discharge (SDD) following bariatric surgery is becoming increasingly more common to reduce healthcare utilization. However, predictors of successful SDD vary across the literature. This study applied machine learning to identify predictors of SDD and evaluate the relative contributions of patient- and procedure-related factors. Patients undergoing sleeve gastrectomy and gastric bypass were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2020 and 2023. Patient, procedure and operative characteristics were analyzed. Synthetic Minority Oversampling Technique was applied given that SDD represented the minority of the cases. Machine learning models including Random Forest, Na&#xef;ve Bayes, Neural Network, Extreme Gradient Boosting (XGBoost), and categorical boosting (CatBoost) were developed to predict SDD. Model performance was evaluated using the area under the receiver operating characteristic curve and compared with multivariable logistic regression. Feature importance was assessed using SHapley Additive exPlanations (SHAP). A total of 768,744 patients underwent bariatric surgery, of whom 66,809 (8.7%) underwent same-day discharge (SDD). SHAP analysis identified operative duration as the strongest predictor of SDD, while baseline patient comorbidities demonstrated comparatively smaller contributions to model predictions. Among machine learning models, CatBoost demonstrated the highest predictive performance (AUC 0.80), followed by XGBoost (AUC 0.79), whereas multivariable logistic regression had the lowest predictive performance (AUC 0.50). We developed a machine learning model that outperformed logistic regression in predicting same-day discharge following bariatric surgery. Operative duration emerged as the most important predictor of discharge status, suggesting that intraoperative events may play a greater role in determining discharge status than preoperative patient comorbidities.

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To explore the active components and potential molecular mechanisms of Xiangsha Liujunzi decoction (XSLJZ) in the treatment of thyroid cancer. Active components and corresponding targets of XSLJZ were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Thyroid cancer-related targets were collected from seven bioinformatics databases, including GeneCards, OMIM, DisGeNET, DrugBank, TCGA, GEO, and TTD. A protein-protein interaction (PPI) network and a multi-level "XSLJZ-medicinal materials-active components-potential targets-thyroid cancer" network were constructed to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking to assess binding affinities. In vitro, CCK-8, flow cytometry, colony formation, Transwell, and Western blotting assays were used to evaluate cell proliferation, death, colony formation, migration, and protein expression in 8505C and TPC-1 thyroid cancer cells. In vivo, a subcutaneous xenograft model was established in female BALB/c nude mice (6-8 weeks old, 15-16 g) by injecting 2&#xd7;106 8505C cells. Mice were randomly divided into model control (vehicle), low-dose XSLJZ (2 mg/kg), and high-dose XSLJZ (4 mg/kg) groups (n=6 per group), receiving daily gavage for 24 days. Tumor volume and body weight were measured every four days. Histopathological changes were observed by HE and immunohistochemical staining. Five major active components of XSLJZ (isoliquiritigenin, naringenin, baicalein, nobiletin, and glycyrrhetinic acid) and 45 core targets for thyroid cancer were identified. XSLJZ and these five components significantly inhibited the proliferation of 8505C and TPC-1 cells without notable toxicity to normal thyroid cells, with isoliquiritigenin showing the most prominent effect. Flow cytometry revealed that XSLJZ (16 mg/mL) induced up to 84.91% death in TPC-1 cells. Molecular docking showed low binding energies between isoliquiritigenin and Akt1, Caspase-3, Caspase-9, and PARP (lowest: &#xff0d;9.9 kcal/mol with PARP). XSLJZ and isoliquiritigenin dose-dependently suppressed colony formation and migration, downregulated RAGE, p-PI3K, and p-Akt, upregulated Bax and mitochondrial cytochrome c, and activated Caspase-3/9-mediated apoptosis and GSDME-dependent pyroptosis via the AGE-RAGE&#x2192;PI3K/Akt axis. In vivo, both low and high doses of XSLJZ significantly inhibited tumor growth, reduced Akt and Ki-67 expression in tumor tissues (all P<0.05), and showed no obvious toxicity to the heart, liver, or kidneys. XSLJZ inhibits thyroid cancer cell proliferation and induces cell death through multi-component, multi-target synergistic regulation of the AGE-RAGE&#x2192;PI3K/Akt signaling pathway. &#x76ee;&#x7684;: &#x63a2;&#x7a76;&#x9999;&#x7802;&#x516d;&#x541b;&#x5b50;&#x6c64;&#xff08;XSLJZ&#xff09;&#x6cbb;&#x7597;&#x7532;&#x72b6;&#x817a;&#x764c;&#x7684;&#x6d3b;&#x6027;&#x6210;&#x5206;&#x53ca;&#x6f5c;&#x5728;&#x5206;&#x5b50;&#x673a;&#x5236;&#x3002;&#x65b9;&#x6cd5;: &#x5229;&#x7528;&#x4e2d;&#x836f;&#x7cfb;&#x7edf;&#x836f;&#x7406;&#x5b66;&#x6570;&#x636e;&#x5e93;&#x4e0e;&#x5206;&#x6790;&#x5e73;&#x53f0;&#xff08;TCMSP&#xff09;&#x7b5b;&#x9009;XSLJZ&#x7684;&#x836f;&#x7269;&#x6709;&#x6548;&#x6d3b;&#x6027;&#x6210;&#x5206;&#x53ca;&#x5176;&#x9776;&#x70b9;&#x3002;&#x8fd0;&#x7528;GeneCards&#x3001;&#x5728;&#x7ebf;&#x4eba;&#x7c7b;&#x5b5f;&#x5fb7;&#x5c14;&#x9057;&#x4f20;&#xff08;OMIM&#xff09;&#x3001;DisGENET&#x3001;DrugBank&#x3001;&#x764c;&#x75c7;&#x57fa;&#x56e0;&#x7ec4;&#x56fe;&#x8c31;&#xff08;TCGA&#xff09;&#x3001;&#x57fa;&#x56e0;&#x8868;&#x8fbe;&#x7efc;&#x5408;&#xff08;GEO&#xff09;&#x6570;&#x636e;&#x5e93;&#x53ca;&#x6cbb;&#x7597;&#x9776;&#x70b9;&#x6570;&#x636e;&#x5e93;&#xff08;TTD&#xff09;&#x7b49;&#x4e03;&#x4e2a;&#x751f;&#x7269;&#x4fe1;&#x606f;&#x5b66;&#x6570;&#x636e;&#x5e93;&#x7b5b;&#x9009;&#x7532;&#x72b6;&#x817a;&#x764c;&#x76f8;&#x5173;&#x9776;&#x70b9;&#x3002;&#x901a;&#x8fc7;&#x6784;&#x5efa;&#x86cb;&#x767d;-&#x86cb;&#x767d;&#x76f8;&#x4e92;&#x4f5c;&#x7528;&#xff08;PPI&#xff09;&#x7f51;&#x7edc;&#x548c;&#x201c;XSLJZ-&#x836f;&#x6750;-&#x6d3b;&#x6027;&#x6210;&#x5206;-&#x6f5c;&#x5728;&#x9776;&#x70b9;-&#x7532;&#x72b6;&#x817a;&#x764c;&#x201d;&#x591a;&#x5c42;&#x6b21;&#x7f51;&#x7edc;&#x7b5b;&#x9009;&#x6838;&#x5fc3;&#x9776;&#x70b9;&#xff0c;&#x5e76;&#x901a;&#x8fc7;&#x57fa;&#x56e0;&#x672c;&#x4f53;&#xff08;GO&#xff09;&#x529f;&#x80fd;&#x6ce8;&#x91ca;&#x3001;&#x4eac;&#x90fd;&#x57fa;&#x56e0;&#x548c;&#x57fa;&#x56e0;&#x7ec4;&#x6570;&#x636e;&#x5e93;&#xff08;KEGG&#xff09;&#x901a;&#x8def;&#x8fdb;&#x884c;&#x5bcc;&#x96c6;&#x5206;&#x6790;&#xff0c;&#x5206;&#x5b50;&#x5bf9;&#x63a5;&#x5206;&#x6790;XSLJZ&#x6d3b;&#x6027;&#x6210;&#x5206;&#x4e0e;&#x9776;&#x70b9;&#x7684;&#x7ed3;&#x5408;&#x80fd;&#x529b;&#x3002;&#x4f53;&#x5916;&#x8bd5;&#x9a8c;&#x4e2d;&#xff0c;&#x901a;&#x8fc7;CCK-8&#x68c0;&#x6d4b;&#x7ec6;&#x80de;&#x6d3b;&#x6027;&#xff0c;&#x6d41;&#x5f0f;&#x7ec6;&#x80de;&#x672f;&#x68c0;&#x6d4b;&#x7532;&#x72b6;&#x817a;&#x764c;&#x7ec6;&#x80de;&#x6b7b;&#x4ea1;&#x60c5;&#x51b5;&#xff0c;&#x514b;&#x9686;&#x5f62;&#x6210;&#x5b9e;&#x9a8c;&#x68c0;&#x9a8c;&#x7532;&#x72b6;&#x817a;&#x764c;&#x7ec6;&#x80de;&#x589e;&#x6b96;&#x80fd;&#x529b;&#xff0c;Transwell&#x5b9e;&#x9a8c;&#x68c0;&#x9a8c;&#x7532;&#x72b6;&#x817a;&#x764c;&#x7ec6;&#x80de;&#x8fc1;&#x79fb;&#x80fd;&#x529b;&#xff0c;&#x86cb;&#x767d;&#x8d28;&#x5370;&#x8ff9;&#x6cd5;&#x68c0;&#x6d4b;&#x76ee;&#x6807;&#x86cb;&#x767d;&#x8868;&#x8fbe;&#x3002;&#x53d6;6~8&#x5468;&#x9f84;&#x96cc;&#x6027;BALB/c&#x88f8;&#x9f20;&#xff08;&#x4f53;&#x91cd;15~16g&#xff09;&#x5efa;&#x7acb;&#x76ae;&#x4e0b;&#x79fb;&#x690d;&#x7624;&#x6a21;&#x578b;&#xff0c;&#x4e8e;&#x88f8;&#x9f20;&#x4fa7;&#x8179;&#x90e8;&#x76ae;&#x4e0b;&#x6ce8;&#x5c04;2&#xd7;10&#x2076;/100 &#xb5;L&#x7684;8505C&#x7ec6;&#x80de;&#x60ac;&#x6d6e;&#x6db2;&#x3002;&#x4e00;&#x5468;&#x540e;&#xff0c;&#x5c06;&#x5c0f;&#x9f20;&#x968f;&#x673a;&#x5206;&#x4e3a;&#x6a21;&#x578b;&#x5bf9;&#x7167;&#x7ec4;&#xff08;&#x7ed9;&#x4e88;&#x8d4b;&#x5f62;&#x5242;&#xff09;&#x3001;XSLJZ&#x5c0f;&#x5242;&#x91cf;&#x7ec4;&#xff08;&#x7ed9;&#x4e88;XSLJZ 2 mg/kg&#xff09;&#x548c;XSLJZ&#x5927;&#x5242;&#x91cf;&#x7ec4;&#xff08;&#x7ed9;&#x4e88;XSLJZ 4 mg/kg&#xff09;&#xff0c;&#x5747;&#x6bcf;&#x65e5;&#x4e00;&#x6b21;&#x704c;&#x80c3;&#xff0c;&#x6301;&#x7eed;24 d&#xff0c;&#x6bcf;&#x7ec4;6&#x53ea;&#x3002;&#x6bcf;&#x56db;&#x5929;&#x6d4b;&#x91cf;&#x4e00;&#x6b21;&#x5c0f;&#x9f20;&#x7684;&#x4f53;&#x91cd;&#x548c;&#x80bf;&#x7624;&#x5927;&#x5c0f;&#x3002;HE&#x67d3;&#x8272;&#x548c;&#x514d;&#x75ab;&#x7ec4;&#x7ec7;&#x5316;&#x5b66;&#x67d3;&#x8272;&#x89c2;&#x5bdf;&#x7ec4;&#x7ec7;&#x75c5;&#x7406;&#x5b66;&#x53d8;&#x5316;&#x3002;&#x7ed3;&#x679c;: 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Migration is one of the most feared complications following lip filler. The use of a specific filler with a high degree of elasticity and cohesiveness could be the key to solve the problem if injections are performed in the correct anatomical plane. The purpose of this study was to describe the authors' 5-year experience with a new concept of lip filling, iLips. This reproducible approach combines elasticity and cohesiveness of a 25,5 mg/ml filler injected through superficial micro-tunnels in a virtual space between orbicularis muscle and mucosa creating a tridimensional net that respects lip dynamic also leading to a low risk of filler migration. A total of 4583 consecutive patients who underwent lip filler with iLips technique were enrolled in this prospective study. An objective evaluation on the aesthetic results was obtained by a jury composed of 3 external plastic surgeons using Lip Fullness Merz scale. PROMs were investigated through FACE-Q administration to the patients ("Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" scales). Statistical analysis was performed through Prism10. Complications were reported. t-test with Welch's correction showed an improvement in Lip Fullness Merz score both in upper and lower lip (p<0.05). A similar trend was shown also for "Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" mean values after the procedure. Just 2 cases of major vascular complications were reported. iLips &#xae; seem to be a safe, highly reproducible, effective and satisfying approach for lip augmentation positively impacting also the patient's psychological sphere. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

This study compared the incidence of intraoperative significant vessel injury between robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) during major pulmonary resection. This retrospective study included 1215 patients who underwent major pulmonary resection via a minimally invasive approach between October 2012 and August 2025 at our institution: 903 underwent VATS (413 uniport, 490 multiport) and 312 underwent RATS. Propensity scores were calculated using preoperative variables, and stabilized inverse probability of treatment weighting (IPTW) was applied. The primary outcome was intraoperative significant vessel injury, defined as bleeding that required additional hemostatic intervention, such as sealant application, clipping, or suturing, after initial compression. Weighted logistic regression was used to assess the association between surgical approach and significant vessel injury. Secondary perioperative outcomes were also compared. After IPTW adjustment, baseline characteristics were well balanced. RATS was associated with a significantly lower risk of intraoperative significant vessel injury than VATS (adjusted odds ratio [OR]: 0.21, 95% confidence interval [CI], 0.08-0.54, P&#x2009;=&#x2009;0.001). In an exploratory three-group analysis, RATS showed a lower risk than multiport VATS (OR: 0.15, 95% CI: 0.06-0.40, P&#x2009;<&#x2009;0.001) and a borderline lower risk than uniport VATS (OR: 0.35, 95% CI: 0.12-1.00, P&#x2009;=&#x2009;0.050). RATS was also associated with more favorable perioperative outcomes. RATS was associated with a lower risk of intraoperative significant vessel injury than VATS and with favorable short-term perioperative outcomes during major pulmonary resection.

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Subcutaneous natalizumab offers greater convenience than intravenous administration, but pharmacokinetic differences have raised concerns about potential subclinical disease activity. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) are sensitive biomarkers of neuroaxonal damage and astroglial activation. In this prospective, single-center cohort study, consecutive patients with relapsing-remitting multiple sclerosis who transitioned from intravenous to subcutaneous natalizumab were followed for 12&#xa0;months. Serum sNfL and GFAP were measured at baseline (prior to switch), and at 6 and 12&#xa0;months using SIMOA technology. Additional clinical outcomes included annualized relapse rate (ARR), EDSS, and MRI activity. 23 patients were included (mean age 43.7&#xa0;years; 91% female). Median disease duration was 14&#xa0;years (IQR 8.1-22), median time on natalizumab was 5&#xa0;years (IQR 3.3-7.9), baseline 2-year ARR was 0.09&#x2009;&#xb1;&#x2009;0.2, and median EDSS was 2.0 (IQR 2.0-3.5). Median sNfL Z-scores were 0.2 (IQR -&#xa0;0.3-0.6) at baseline, 0.1 (IQR -&#xa0;0.4-1.0) at 6&#xa0;months, and 0.5 (IQR -&#xa0;0.4-1.1) at 12&#xa0;months, with no significant change over time (p&#x2009;=&#x2009;0.401). GFAP levels were similarly stable (87.7, 86.8, and 90.2&#xa0;pg/mL; p&#x2009;=&#x2009;0.957). ARR remained low and unchanged (0.09 pre- and post-switch; p&#x2009;=&#x2009;1.0), with no radiological activity observed. EDSS remained stable over follow-up. In this small real-world cohort, switching from intravenous to subcutaneous natalizumab was associated with stable sNfL and GFAP levels over 12&#xa0;months, alongside stable conventional clinical and MRI outcomes. These findings provide supplementary biomarker evidence broadly consistent with existing clinical trial and real-world data, but should be interpreted cautiously given the small sample size.

Activating mutations in the RAS-MAPK pathway account for ~20% of cases of pediatric hypertrophic cardiomyopathy (HCM) and are associated with poor outcomes. Mavacamten is approved for obstructive HCM; however, patients with RAS-associated HCM have not been included in the clinical trials so far. We aimed to characterize the functional and energetic disturbances in an in vitro RAS-HCM model and evaluate the therapeutic effects of mavacamten. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying a CRISPR-induced BRAF (p.Thr599Arg) mutation and their isogenic control were studied. Cell size, contractility, and transcriptomics were assessed, while energetics were determined using MitoStress assays, live ATP imaging, and NAD(P)H/FAD autofluorescence. BRAF-mutant hiPSC-CMs showed hypertrophy, hypercontractility, increased mitochondrial cofactor pools, and enhanced maximal respiratory capacity. Despite this, they developed ATP deficiency in response to rapid pacing, suggesting mitochondrial inefficiencies or an overwhelming ATP demand. Mavacamten normalized mitochondrial respiration and excessive ATP consumption, partially restoring energetic balance and highlighting hypercontractility as a major burden in RAS-HCM. BRAF-mutant cardiomyocytes recapitulate the characteristics of HCM in vitro. Mavacamten mitigates dysfunctions and restores energetic balance under stress conditions, indicating it holds potential as a therapeutic option for RASopathy-associated HCM. BRAF-mutant hiPSC-CMs exhibit hypertrophy, hypercontractility, and energetic imbalance under stress, reproducing pathological characteristics of RAS-HCM. Mitochondrial stress tests showed a higher basal respiration and maximal respiratory capacity, indicating that mitochondrial dysfunction is not the main cause of this imbalance. Mavacamten normalized basal mitochondrial respiration and ATP utilization under stress, indicating that hypercontractility represents a major energetic burden. The beneficial effects of mavacamten on BRAF-mutant hiPSC-CMs suggest therapeutic potential for treating RASopathy-associated HCM.

Fungal infections, especially in people with weakened immune systems, are a significant global health burden. Accurate identification of fungal morphology from microscopic images is a critical step in guiding timely antifungal treatment decisions. However, manual morphological assessment remains highly dependent on expert mycologists and is prone to inter-observer variability. In this study, we propose a hybrid deep learning framework that integrates the ConvNeXtV2-Base architecture with a Multi-Head Attention-based Multiple Instance Learning module for automated classification of microscopic fungal morphology images. The framework was evaluated on the open-access DeFungi dataset, consisting of 3696 microscopic images representing five clinically meaningful fungal morphology classes. In comparative experiments, classical vision transformer (ViT) models achieved 91.20% accuracy, while MIL-enhanced ViT models reached 93.99%. The proposed ConvNeXtV2-Base&#x2009;+&#x2009;MIL hybrid method outperformed all evaluated architectures, achieving 98.90% classification accuracy. These results establish a new benchmark for automated fungal morphology classification and highlight the potential of AI-assisted decision-support tools to aid expert mycologists in morphology-based assessment workflows.