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Abstract Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA-seq) and high-throughput chromosome conformation capture (Hi-C) sequencing. Over 10,000 cells were profiled via scRNA-seq, revealing the comprehensive B cell transformation in RS. Hi-C sequencing exposed a unique chromatin architecture in RS, with increased proximal and decreased distal interactions. At the compartment scale, the interaction between B compartments was strengthened in DLBCL cells, while topologically associating domains (TADs) in DLBCL had elevated intra-TAD and reduced inter-TAD contacts. Differentially expressed genes at TAD borders between CLL and DLBCL cells highlighted an enrichment of cAMP-mediated signalling. To substantiate the functional relevance of ATF1 and CAP1, the genes involve in cAMP-mediated signalling, in the context of cell proliferation, we have performed gain- and loss-of-function experiments in relevant cell lines. Collectively, integrated scRNA-seq and Hi-C data suggest that chromatin reorganization and altered cAMP signalling drive RS transformation.

Abstract Surface soil moisture is projected to decrease under global warming. Such projections are mostly based on climate models, which show large uncertainty (i.e., inter-model spread) partly due to inadequate observational constraint. Here we identify strong physically-based emergent relationships between soil moisture change (2070–2099 minus 1980–2014) and recent air temperature and precipitation trends across an ensemble of climate models. We extend the commonly used univariate Emergent Constraints to a bivariate method and use observed temperature and precipitation trends to constrain global soil moisture changes. Our results show that the bivariate emergent constraints can reduce soil moisture change uncertainty by 7.87%, which is four times more effective than traditional temperature-based univariate constraints. The bivariate emergent constraints change the sign of soil moisture change from negative to positive for semi-arid, dry sub-humid and humid regions and global land as a whole, but exacerbates the drying trend in arid and hyper-arid regions.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide. The pan-immune-inflammation value (PIV) has been proposed as a biomarker for assessing immune status and inflammation. There is currently no evidence regarding the effect of PIV on the risk of MASLD. This study aimed to investigate the association between PIV and MASLD. Methods The cross-sectional study included 6462 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey 2017–2020. PIV was calculated based on blood count data. Weighted multivariable logistic regression was employed to calculate the odds ratio (OR) and 95% confidence interval (CI) to investigate the association of PIV and MASLD. Restricted cubic spline (RCS) analysis was conducted to explore the dose-response relationship between PIV and MASLD. Stratified and sensitivity analyses were performed to confirm the robustness of our findings. Results Among 6462 participants, 2458 were diagnosed with MASLD. Positive associations between LnPIV and MASLD were observed in all three models (Model 1: OR = 1.46, 95% CI: 1.28–1.66, P

Abstract Background Primary mediastinal liposarcomas (PLMs) are extremely rare. Patients typically present with symptoms caused by tumor size, as the mass can compress surrounding tissues and organs. Here, we report a case of a large primary mediastinal liposarcoma that was successfully resected thoracoscopically. By reviewing the available literature on mediastinal liposarcomas and sharing perioperative insights, we aim to provide guidance on the diagnosis and surgical management of large mediastinal liposarcomas. Case presentation A 38-year-old male presented to our hospital with complaints of dysphagia after meals. Chest computed tomography (CT) revealed a large space-occupying lesion in the posterior upper mediastinum, and gastroscopy identified esophageal compression without evidence of new growth. The patient underwent thoracoscopic resection, resulting in significant improvement of his dysphagia postoperatively. He experienced no postoperative complications and was discharged one week following surgery. Conclusion The incidence of PLM is very low. Due to the proximity of vital structures such as the vena cava, esophagus, trachea, and subclavian artery, surgical resection presents elevated risks and complexity. While minimally invasive thoracoscopic techniques offer both safety and efficacy, careful preservation of surrounding organs is essential during the procedure.

Background: Metrics to successfully predict pediatric decannulation have been ineffective. The Functional Status Scale (FSS) is a validated pediatric scoring system of functional outcomes. The objective of this study was to evaluate if the FSS over time predicts pediatric tracheostomy decannulation. Subjects and Methods: Chart review of patients admitted to the pediatric intensive care unit (PICU) and underwent tracheostomy at a tertiary care children’s hospital from 2010 to 2019. Baseline demographics, comorbidities, tracheostomy indication, decannulation status, and FSS scores were recorded at PICU discharge and 1 and 3 years after tracheostomy. Logistic regression was performed to assess the association of FSS components with decannulation status at 3 years. Results: Fifty-three patients met the inclusion criteria. Forty (75.5%) patients had complete data. There were no decannulations at 1 year. Nine (22.5%) patients were decannulated at 3 years. An abnormal 3-year FSS score in the feeding domain was significantly associated with persistent tracheostomy at 3 years, with an odds ratio of 7.4 (95% confidence interval: 1.5–36.6, P = 0.01). Conclusions: FSS score can predict decannulation in children discharged from the PICU. This information could modify caregiver expectations and guide rehabilitative efforts.

Abstract Background Decision-making in the management of Crohn’s disease (CD)-related spontaneous intra-abdominal abscess (IAA) is challenging. This study aims to reveal predictive factors for percutaneous drainage and/or surgery in the treatment of CD-related spontaneous IAA through long-term follow-up. Methods Data were collected, including clinical manifestations, radiography and treatment strategies, in Chinese patients with CD-related IAA in a tertiary medical center. Univariate and Multivariate Cox analysis were conducted to identify predictors for invasive therapy. Results Altogether, 48 CD patients were identified as having IAA through enhanced CT scans. The median follow-up time was 45.0 (23.3, 58.0) months. 23 (47.9%) patients underwent conservative medical treatment, and 25 (52.1%) patients underwent percutaneous drainage and/or surgical intervention (invasive treatment group). The 1-, 2-, and 5-year overall survival rates without invasive treatment were 75.0%, 56.1%, and 46.1%, respectively. On univariate Cox analysis, the computerized tomography (CT) features including nonperienteric abscess (HR: 4.22, 95% CI: 1.81–9.86, p = 0.001), max abscess diameter (HR: 1.01, 95% CI: 1.00-1.02, p

Abstract The incidence of multiple primary lung cancer (MPLC) is increasing, with some of our surgical patients exhibiting numerous lesions. We defined lung cancer with five or more primary lesions as super MPLCs. Elucidating the genomic characteristics of this special MPLC subtype can help reduce disease burden and understand tumor evolution. In our cohort of synchronous super early-stage MPLCs (PUMCH-ssesMPLC), whole-exome sequencing on 130 resected malignant specimens from 18 patients provided comprehensive super-MPLC genomic landscapes. Mutations are enriched in PI3k-Akt and MAPK pathways. Their BRAF mutation frequency (31.5%) is significantly higher than MPLC with fewer lesions and early-stage single-lesion cancer, while EGFR mutations are significantly fewer (13.8%). As lesion counts increase, BRAF mutations gradually become dominant. Also, invasive lesions more tend to have classic super-MPLC mutation patterns. High-frequency BRAF mutations, especially Class II, and low-frequency EGFR mutations could be a reason for the limited effectiveness of targeted therapy in super-MPLC patients.

Abstract Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Abstract Background Traditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases. Methods Here, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs. Results We found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9. Conclusion Au-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.

Abstract The increasing complexity and high-dimensional nature of real-world optimization problems necessitate the development of advanced optimization algorithms. Traditional Particle Swarm Optimization (PSO) often faces challenges such as local optima entrapment and slow convergence, limiting its effectiveness in complex tasks. This paper introduces a novel Hybrid Strategy Particle Swarm Optimization (HSPSO) algorithm, which integrates adaptive weight adjustment, reverse learning, Cauchy mutation, and the Hook-Jeeves strategy to enhance both global and local search capabilities. HSPSO is evaluated using CEC-2005 and CEC-2014 benchmark functions, demonstrating superior performance over standard PSO, Dynamic Adaptive Inertia Weight PSO (DAIW-PSO), Hummingbird Flight patterns PSO (HBF-PSO), Butterfly Optimization Algorithm (BOA), Ant Colony Optimization (ACO), and Firefly Algorithm (FA). Experimental results show that HSPSO achieves optimal results in terms of best fitness, average fitness, and stability. Additionally, HSPSO is applied to feature selection for the UCI Arrhythmia dataset, resulting in a high-accuracy classification model that outperforms traditional methods. These findings establish HSPSO as an effective solution for complex optimization and feature selection tasks.

Abstract This paper proposes a method of impulse current generator modulated DC arc by combining the advantages of pulse and the RF to solve the low electron energy problem of direct current arc. Through experimental analyzing the electrical, spectral, and optical characteristics of the arc, the effect of impulse current generator (ICG) on improving electron energy is discussed. The results show that the ICG consumes more energy to enhance the strength of arc discharge, and therefore electron energy is increased in a microsecond scale. In addition, it is found that the electron energy of the arc discharge can be adjusted by varying inductance, capacitance, and discharge tube: increasing the inductance or capacitance can increase the electron energy firstly and then decrease it. In adjusting the three adjustable components, adjusting the inductor is the most effective method, followed by adjusting the capacitor, and adjusting the repetition frequency has the least effect. The reason is discussed, and it is believed that the results are related to leakage inductance and distributed capacitance.

Abstract This study aims to develop machine learning (ML)-assisted models for analyzing datasets related to Gleason scores in prostate cancer, conducting statistical analyses on the datasets, and identifying meaningful features. We retrospectively collected data from 717 hormone-sensitive prostate cancer (HSPC) patients at Yunnan Cancer Hospital. Of these, data from 526 patients were used for modeling. Seven auxiliary models were established using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), Extreme gradient boosting tree (XGBoost), Adaptive Boosting (Adaboost), and artificial neural network (ANN) based on 21 clinical biochemical indicators and features. Evaluation metrics included accuracy (ACC), precision (PRE), specificity (SPE), sensitivity (SEN) or regression rate(Recall), and f1 score. Evaluation metrics for the models primarily included ACC, PRE, SPE, SEN or Recall, f1 score, and area under the curve(AUC). Evaluation metrics were visualized using confusion matrices and ROC curves. Among the ensemble learning methods, RF, XGBoost, and Adaboost performed the best. RF achieved a training dataset score of 0.769 (95% CI: 0.759—0.835) and a testing dataset score of 0.755 (95% CI: 0.660—0.760) (AUC: 0.786, 95%CI: 0.722—0.803), while XGBoost achieved a training dataset score of 0.755 (95% CI: 95%CI: 0.711—0.809) and a testing dataset score of 0.745 (95% CI: 0.660—0.764) (AUC: 0.777, 95% CI: 0.726—0.798). Adaboost scored 0.789 on the training dataset (95% CI: 0.782—0.857) and 0.774 on the testing dataset (95% CI: 0.651—0.774) (AUC: 0.799, 95% CI: 0.703—0.802). In terms of feature importance (FI) in ensemble learning, Bone metastases at first visit, prostatic volume, age, and T1-T2 have significant proportions in RF’s FI. fPSA, TPSA, and tumor burden have significant proportions in Adaboost’s FI, while f/TPSA, LDH, and testosterone have the highest proportions in XGBoost. Our findings indicate that ensemble learning methods demonstrate good performance in classifying HSPC patient data, with TNM staging and fPSA being important classification indicators. These discoveries provide valuable references for distinguishing different Gleason scores, facilitating more accurate patient assessments and personalized treatment plans.

Abstract Patients with neurogenic rosacea (NR) frequently demonstrate pronounced neurological manifestations, often unresponsive to conventional therapeutic approaches. A molecular-level understanding and diagnosis of this patient cohort could significantly guide clinical interventions. In this study, we amalgamated our sequencing data (n = 46) with a publicly accessible database (n = 38) to perform an unsupervised cluster analysis of the integrated dataset. The eighty-four rosacea patients were partitioned into two distinct clusters. Neurovascular biomarkers were found to be elevated in cluster 1 compared to cluster 2. Pathways in cluster 1 were predominantly involved in neurotransmitter synthesis, transmission, and functionality, whereas cluster 2 pathways were centered on inflammation-related processes. Differential gene expression analysis and WGCNA were employed to delineate the characteristic gene sets of the two clusters. Subsequently, a diagnostic model was constructed from the identified gene sets using linear regression methodologies. The model's C index, comprising genes PNPLA3, CUX2, PLIN2, and HMGCR, achieved a remarkable value of 0.9683, with an area under the curve (AUC) for the training cohort's nomogram of 0.9376. Clinical characteristics from our dataset (n = 46) were assessed by three seasoned dermatologists, forming the NR validation cohort (NR, n = 18; non-neurogenic rosacea, n = 28). Upon application of our model to NR diagnosis, the model's AUC value reached 0.9023. Finally, potential therapeutic candidates for both patient groups were predicted via the Connectivity Map. In summation, this study unveiled two clusters with unique molecular phenotypes within rosacea, leading to the development of a precise diagnostic model instrumental in NR diagnosis.

Abstract Background Anaplastic lymphoma kinase (ALK) test in advanced non‐small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real‐world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. Methods In this real‐world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)‐VENTANA‐D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. Results The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC‐VENTANA‐D5F3 revealed an intra‐hospital consistency rate of 98.2% (879/895) and an inter‐hospital consistency rate of 99.2% (646/651). IHC‐VENTANA‐D5F3 was used in 53.6%, real‐time polymerase chain reaction (RT‐PCR) in 25.4%, next‐generation sequencing (NGS) in 18.3%, and fluorescence in‐situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC‐VENTANA‐D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT‐PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). Conclusions This study highlights the real‐world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC‐VENTANA‐D5F3 with high consistency and distinct clinicopathological features in ALK‐positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision‐making in NSCLC.

Chimeric antigen receptor (CAR) T cells have encouraging results in the treatment of hematological malignancies. However, CAR-T therapy still faces numerous challenges against solid tumors, such as hepatocellular carcinoma (HCC), owing to heterogeneous antigen expression in tumor cells, limited persistence of CAR-T cells, etc. Therefore, to treat HCC more effectively, we connected the molecular receptor NKBB to a second-generation glypican-3 (GPC3) CAR to construct GC3328z-NKBB CAR-T cells, which have double specific targets of GPC3 and NKG2DLs (natural killer group 2, member D ligands), dual co-stimulation of CD28 and 41BB, and a single CD3ζ chain. Our study showed that the molecular receptor NKBB conferred GPC3 CAR-T cells with enhanced migration and infiltration abilities towards HCC, higher central memory T (TCM) cell proportion and proliferation capacity, and reduced exhaustion level. GC3328z-NKBB CAR-T cells exhibited improved cytotoxicity against HCC cells and prolonged persistence. The cathepsin L/interleukin-17 (CTSL/IL-17) axis contributed to the superior anti-HCC activity of GC3328z-NKBB CAR-T cells. Overall, the molecular receptor NKBB significantly increased the persistence of GPC3 CAR-T cells, and GC3328z-NKBB CAR-T cells possessed potent anti-HCC activity in mice, providing a new strategy for the potential improvement of adoptive T cell therapy in the treatment of HCC.

Background: The presence of level IV/V metastasis is a significant prognostic factor for patients with oral and oropharyngeal cancer, while level IV lymphadenopathy defines the N3 stage in nasopharyngeal carcinoma. However, the current staging system for hypopharyngeal squamous cell carcinoma (HPSCC) does not consider the location of involved nodes. Objectives: To evaluate the risk factors and prognostic impact of level IV/V metastasis in patients with HPSCC. Methods: The analysis included 2740 HPSCC patients from the SEER (Surveillance, Epidemiology, and End Results) database, followed by a validated study on 232 patients with pathologically positive nodes (pN+) at our center. Results: Of the 2740 patients, 1961 presented with metastatic lymph nodes (LNs), 20.8% and 14.1% had nodal involvement in level IV and level V, respectively. Multivariate analysis revealed that N3 and M1 stages were independently associated with level IV/V metastasis. Level IV metastasis was the sole independent adverse factor for overall survival (OS) among all LN regions ( p

ObjectiveTo explore the impact of aerobic and resistance training on walking and balance abilities (UPDRS-III, Gait Velocity, Mini-BESTest, and TUG) in individuals with Parkinson's disease (PD).MethodAll articles published between the year of inception and July 2024 were obtained from PubMed, Embase, and Web of Science. Meta-analysis was conducted with RevMan 5.4.ResultResearch from 15 randomized controlled trials, comprising 792 older patients with a diagnosis of PD, was included in the analysis. Aerobic training (AT) and Resistance training (RT) significantly improved UPDRS-III (AT, SMD = -5.69, 95% CI: -8.67 to -2.71, p = 0.0002, I2 = 82%; RT, SMD = -3.01, 95% CI: -4.89 to -1.12, p = 0.002, I2 = 0%) and Gait Velocity(AT, SMD = 0.88, 95% CI: 0.58 to 1.18, p < 0.00001, I2 = 42%; RT, SMD = 0.52, 95% CI: 0.10 to 0.94, p = 0.01, I2 = 55%). AT showed no difference in Mini-BESTest (AT, SMD = 2.12, 95% CI: -0.70 to 4.94, p = 0.14, I2 = 90%). RT showed no change in TUG (RT, SMD = -0.03, 95% CI: -1.60 to 1.54, p = 0.97, I2 = 63%).ConclusionsResistance training stood out as the most effective approach to boost performance on the mini-BESTest. Conversely, aerobic exercise proved to be superior for improving the UPDRS-III, gait velocity and TUG scores.

Wetlands are among the most productive ecosystems and play crucial roles in relation to biodiversity conservation and various ecosystem services. However, rapid urbanization and environmental changes have led to the loss of a significant number of wetlands, making it imperative to understand the driving forces behind wetland changes. This study employed Partial Least Squares Structural Equation Modeling (PLS-SEM) and the Patch-generating Land Use Simulation (PLUS) model to investigate the influences of natural factors and urbanization on wetland distribution. Based on the driving factors, simulations were conducted for three scenarios—Natural Increase Scenario (NIS), Economic Development Scenario (EDS), and Wetland Protection Scenario (WPS)—projecting the wetland distribution in the Sanjiang Plain until 2050. Results indicate that from 1990 to 2020, the wetland area increased by 9,548.58 km2, with paddy fields increasing by 12,995.73 km2 and marsh wetlands decreasing by 1,031.9 km2. The factors driving wetland distribution varied across different periods. Between 1990 and 2000, topography and urbanization significantly influenced wetland distribution, whereas climate factors became gradually more significant between 2010 and 2020. Furthermore, in addition to exerting direct impacts on wetland distribution, urbanization and climate factors can indirectly affect wetland distribution by influencing topography and soil. Future development scenarios indicate an inevitable increase in paddy field areas and decrease in wetland areas. This framework provides an effective approach for exploring regional wetland changes and supporting regional wetland conservation and future sustainable development.

Objectives To investigate the relationship between drinks behavior and female androgenetic alopecia (AGA) and to clarify the mediating effect of sleep behavior on such relationship. Methods A total of 308 female AGA patients and 305 female normal controls were recruited from the hospital, and questionnaires including drinks behavior and sleep behavior were inquired among them. Blood sugar and blood lipids were detected. Then, the mediating effect of sleep behavior on the relationship between drinks behavior and AGA was analyzed. Results Female AGA patients presented a higher frequency of intake of sweetened tea drinks. It was found that occasional intake (1–2 times per week; ORadj = 2.130, 95% CI [1.495–3.033]) and frequent intake (3–6 time per week; ORadj = 2.054, 95% CI [1.015–4.157]) of sweetened tea drinks were associated with AGA. The daily sugar intake from soft drinks increased the risk of AGA (ORadj = 1.025, 95% CI [1.003–1.048]), and hyperglycemia was positively associated with alopecia (ORadj = 1.897, 95% CI [1.225–2.936]). In addition, bedtime after 12 pm significantly increased the risk of developing alopecia (ORadj = 2.609, 95% CI [1.020–6.676]). Interestingly, bedtime, instead of daily sugar intake from soft drinks, could mediate the relationship between sweetened tea drinks intake and alopecia. Conclusions Sweetened tea drinks consumption increases the risk of female AGA, which is mediated by bedtime.

Laser-activated selective electroless plating (LASELP) is a promising complementary manufacturing process employed in hybrid additive manufacturing (HAM) technology for the fabrication of customized 3D electronics. However, to the best knowledge of the authors, most current LASELP technologies could only enable copper deposition on/within the polymer matrix, which largely limited the application scope of this technology. Accordingly, an advanced LASELP technology combining catalyst exchanging process is proposed to pattern diverse functional metals on the photopolymer to fabricate 3D electronics. Two kinds of catalyst systems are selected in this HAM technology: (1) Cu2(OH)PO4; (2) antimony tin oxide (ATO) and titania (TiO2). Silver and nickel-phosphorus (Ni-P) alloy are selected as the representatives of direct- and indirect-ELP metals, respectively. Silver could be directly plated on the laser-activated surface to deposit a dense and highly conductive layer, while for the Ni-P layer an inevitable catalyst exchange step is applied here to induce Pd0 plating seeds on the laser-activated substrate. Finally, a variety of customized electronics, such as conformal circuit boards, smart structure with strain sensor, embedded structural thermometer, Internet of Things bottle cap, and gas tube integrated with 3D conformal NO2 sensor are fabricated and fully verify this HAM technology.

Background A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited.Objectives To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA.Methods In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature.Results We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported.Conclusions Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab’s successful treatment response.

Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes.

Abstract Background Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. Methods A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. Results A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. Conclusions Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients.

Abstract In recent years, significant improvement has been made in the management of non‐small cell lung cancer (NSCLC), primarily driven by advances in targeted therapy and immunotherapy. Research on neoadjuvant targeted therapy has also experienced considerable development, primarily directed towards NSCLC harboring epidermal growth factor receptor or anaplastic lymphoma kinase mutations. Nevertheless, there remains a dearth of studies investigating neoadjuvant targeted therapy in the context of BRAF (V‐Raf murine sarcoma viral oncogene homolog B) V600E mutant NSCLC. Herein, we describe the clinical trajectory of a stage IIIA NSCLC patient who underwent a two‐month course of neoadjuvant targeted therapy comprising BRAF and MEK (mitogen‐activated extracellular signal‐regulated kinase) inhibitors prior to surgical intervention, and subsequent postoperative evaluation unveiled a pathological complete response. The case reported here indicates the efficacy and safety of combining BRAF and MEK inhibitors as neoadjuvant targeted therapy in BRAF V600E‐mutant NSCLC and suggests the potential viability of such a therapeutic modality in improving treatment outcomes in this subset of NSCLC.

Single-atom catalysts (SACs) exhibit outstanding catalytic activity due to their highly dispersed metal centers. Activating persulfates (PS) with SACs can generate various reactive oxygen species (ROS) to efficiently degrade emerging organic contaminants (EOCs) in aqueous environments, offering unique advantages such as high reaction rates and excellent stability. This technique has been extensively researched and holds enormous potential applications. In this paper, we comprehensively elaborated on the synthesis methods of SACs and their limitations, and factors influencing the catalytic performance of SACs, including metal center characteristics, coordination environment, and types of substrates. We also analyzed practical considerations for application. Subsequently, we discussed the mechanism of SACs activating PS for EOCs degradation, encompassing adsorption processes, radical pathways, and non-radical pathways. Finally, we provide prospects and outline our vision for future research, aiming to guide advancements in applying this technique. HIGHLIGHTS Summarized the synthesis methods of single-atom catalysts and limitations.; Discussed the factors influencing the performance of single-atom catalysts and practical factors.; Elucidated the mechanism of SACs activating PS for EOCs degradation and prospects for the future.;

Abstract Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd−/−) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Abstract Background Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. Methods DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Results Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Abstract Background Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment. Methods We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes’ expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR. Results Twenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies. Conclusions By employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.

Abstract Background Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. Methods The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People’s Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Results A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804–0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. Conclusion In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.

With the merits of both solid polymer electrolytes (SPEs) and inorganic ceramic electrolytes (ICEs), composite polymer electrolytes (CPEs) prepared by coupling polymer matrix with inorganic fillers are broadly utilized in solid lithium metal batteries (SLMBs). However, CPEs fabricated by a single filler with polymer matrix often exhibit unsatisfactory performance. Here, prepared by coupling poly (ethylene oxide) (PEO) matrix with a natural additive carboxymethyl cellulose lithium (CMC-Li) and an inorganic filler mineral hectorite (Ht), an efficient CPE is reported. Detailedly, CMC-Li is considered to act as a “bridge”, which connects the Ht nanosheets distributed in PEO, thus establishing continuous Li+ transmission channels. Ht with a nanolayers structure vividly acts as “bricks”, pave the way for ion transference. In addition, oxygen atoms in CMC-Li contribute to adequately dissociating lithium salts, hydrogen bonding generated by hydroxyl groups is propitious to anchor anions to increase the Li+ transference number. Under the synergistic effect brought by CMC-Li and Ht, the electrolyte membrane PEO-10%Ht-4%CMC-Li (PHCL, in mass fraction) displays a high Li+ transfer number (0.73) and exceptional Li+ conductivity at 25 °C (2.5 × 10−4 S/cm). Our work demonstrates a powerful mean to fabricate the efficient electrolyte membrane for SLMBs.

Objective: COVID-19 remains a significant health threat to the United States (U.S.) and the world even after the development of effective vaccines. Throughout the pandemic, rural areas have been more hesitant to be vaccinated for COVID-19 than more urban counterparts. The purpose of this study was to assess predictors of vaccine hesitancy in a small, largely rural, southern state using a multivariate model that would allow an assessment of independent predictors of COVID-19 vaccine hesitancy. Methods: Cross-sectional survey research was conducted using data collected from a weighted random sample of 1500 individuals residing in Arkansas, U.S. Data were collected using random digit dialing of landline and cell phone numbers between July 12 and July 30, 2021. Participants were asked about their hesitancy to be vaccinated for COVID-19. Data were analyzed using bivariate odds ratios and cumulative logit model. Results: Results found 47 % of the sample were hesitant to be vaccinated. Bivariate analysis found vaccine hesitancy to be related to age, race/ethnicity, rural residence, education, employment, and having had COVID-19. Multivariate analysis showed sex, age, rural residence, and history of having had COVID-19 were associated with hesitancy. A history of vaccination/trust in vaccines remained strongly negatively associated with hesitancy. Conclusion: Findings suggest population diversity may account for vaccine hesitancy across jurisdictions, suggesting public health messages be tailored to a local audience. The strongest finding suggests vaccinations should be emphasized in general to build habits of being vaccinated.

Castleman disease (CD) is a heterogeneous hematological condition characterized by distinctive histopathological features. The etiology remains unclear, and clinical symptoms are generally nonspecific. CD can occur in any location containing lymphatic tissue, with the mediastinum being the most common site, while adrenal involvement is rare. Adrenal CD is typically incidentally discovered during physical examination, commonly affecting one side. Imaging studies often make it challenging to differentiate from common adrenal tumors, necessitating pathological confirmation. Surgical intervention is the preferred treatment, and the prognosis is generally favorable.This paper presents a rare case of a left adrenal mass, which was diagnosed as Castleman disease following surgical resection.

Background Sesn2 (Sestrin2) is a stress‐induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2‐mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R. Methods and Results In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild‐type (WT) and cardiac‐specific Sesn2 knockout (Sesn2cKO) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4‐phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post‐I/R. Hearts from Sesn2cKO mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2cKO hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin‐induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2cKO mice. Conclusions Sesn2 attenuates cardiac ER stress post‐I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.

This study aimed to investigate the impact of incorporating mature compost on the harmlessness and maturity level of composting from swine manure and carcasses from industrialized pig farms in continuously running large-scale silo reactor systems. The potential human or animal bacterial pathogens and core bacterial community in composting were analyzed by high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the addition of mature compost in the GD group significantly increased the temperature of all depths, the accumulated temperature of compost, and the germination index (75.43%) compared to that in the HN group without mature compost. High-throughput sequencing revealed that the dominated genera in GD were Ureibacillus, Lactobacillus, Corynebacterium, Staphylococcus, and Jeotgalicoccus, and the addition of mature compost could significantly increase the relative abundance of Ureibacillus (16.82%) that was associated with the biodegradation of organics. A total of 421 potential bacterial pathogens were detected, and the dominated genera of pathogens were Streptococcus, Staphylococcus, and Anaerococcus. The potential pathogen in the GD group with mature compost was reduced from 7.16 to 0.77%, which was significantly lower than that (2.97%) in the HN group. Together, these findings revealed that mature compost addition in large-scale reactor composting could accelerate the harmless and humification process, providing an effective and environmentally friendly scheme to deal with the main organic wastes in intensive pig farms.

IntroductionThis study investigates the effectiveness of government environmental audits in mitigating air pollution. Specifically, it focuses on a pilot project conducted in Lanzhou City by the former Ministry of Environmental Protection. The research employs a regression discontinuity design to empirically assess the impact of these audits on air quality.MethodsThe study utilizes a regression discontinuity design to evaluate the impact of the government environmental audits. The primary outcome variable is the Air Quality Index (AQI). The analysis includes extensive robustness checks, such as sensitivity testing for optimal bandwidths of key pollutants, adjusting for precipitation levels, and conducting various robustness tests to ensure the reliability of the results.ResultsThe findings reveal a significant decline in the AQI following the implementation of the environmental audits. The AQI decreased from 31 to 25 during and after the audit period. Additionally, the study observed a notable increase in precipitation levels, suggesting potential environmental improvements. Robustness tests further confirm the reliability of the regression results.DiscussionThe research outcomes demonstrate the effectiveness of government environmental audits in reducing air pollution. By supervising local governments in the implementation of environmental protection policies, these audits contribute to improved air quality. The findings highlight the importance of targeted interventions and policy enforcement in addressing environmental challenges.

This paper introduces a comprehensive and resilient multi-energy system (MES) designed for independent planning and real-time implementation. A robust daily coordinated planning model is proposed, incorporating adjustable optimization with fundamental operational and uncertainty constraints. The model integrates various energy sources and systems, including photovoltaics, wind turbines, combined heat and power (CHP) units, energy storage system (ESS), electric vehicle (EV), electric boilers, and power-to-gas (P2G) facilities, to manage electricity, natural gas, and heat demands. The objective is to minimize MES operational costs while meeting electricity and heat requirements, considering renewable energy uncertainties. It includes the development of a two-stage flexible robust optimization model that accounts for energy equilibrium, capacity constraints, and demand response mechanisms. The model incorporates price-based demand response with both switchable and interruptible loads, enhancing system controllability and flexibility. Additionally, a scenario generation and reduction technique based on the Kantorovich distance is employed to effectively manage forecast errors and uncertainties. A novel modified Slime Mold Algorithm (SMA) is utilized to solve the optimization problem, demonstrating superior convergence and computational efficiency compared to traditional meta-heuristics. The slime mold algorithm is further enhanced with chaos theory, using a sine map to introduce dynamic exploration capabilities. The findings indicate that the proposed multi-energy system model effectively balances electricity, natural gas, and heat loads while accommodating renewable energy fluctuations. The enhanced slime mold algorithm provides optimal solutions swiftly, ensuring reliable and cost-effective multi-energy system operation.

BackgroundTraditional Chinese medicine (TCM) is used to treat mycoplasma pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment.MethodWe retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023. Data extraction and quality assessment of the enrolled studies were independently by two reviewers. Review Manager 5.3 was used for meta-analysis.ResultA total of 51 RCTs involving 5,799 children aged 1–14 enrolled. Meta-analysis demonstrated that TCM combined with AZM improved the cure rate (odds ratio [OR] = 2.34, 95% CI: 2.06 to 2.64) and the effective rate (OR = 5.21, 95% CI: 4.22 to 6.43), shorted the disappearance duration of cough (WMD = −1.62, 95% CI: −1.90 to −1.34), the duration of fever (WMD = −1.62, 95% CI: −1.96 to −1.29), and the disappearance time of lung rales (WMD = −1.15, 95% CI: −1.32 to −0.98), improved CRP levels (WMD = −2.06, 95% CI: −2.57 to −1.55), IL-6 levels (WMD = −1.92,95% CI: −2.51 to −1.34), and TNF-α levels (WMD = −1.59, 95% CI: −2.14 to −1.04), and reduced adverse reactions (OR = 0.37, 95% CI: 0.32 to 0.44).ConclusionTCM combined with AZM in the treatment of MP among children has favorable clinical efficacy and safety.

ABSTRACT Background This study aimed to identify a specific SCLC population that would benefit from surgery. Methods This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan–Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer–specific survival (LCSS), respectively. Outcomes Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35–63 months vs. 27 months; 95% CI: 21–33 months, p

Objective Unintentional injuries constitute a significant global public health issue with significant social and economic costs. Previous evidence suggests ambient temperatures are associated with unintentional injury occurrences. However, the impacts of ambient temperature on unintentional injury economic burden have received little research attention. The objective of the study was to examine the association between ambient temperature and economic burden of unintentional injury.Design Time-stratified case-crossover study.Setting This study was performed at Tianjin Hospital, the largest trauma centre in Tianjin, by applying a hospital-based time-stratified case-crossover study.Participants The 12 241 patients admitted with unintentional injuries and meteorological data were collected in Tianjin, China in 2021.Primary and secondary outcome The association between ambient temperature and unintentional injury hospitalisation was evaluated with a distributed lag non-linear model, further temperature-attributable economic burden of unintentional injuries was quantified, and adjusted for demographic characteristics, injury mechanism and injury location of injury.Results The temperatures below 11.5°C were significantly associated with the increased risk of unintentional injury hospitalisation in Tianjin, in 2021. The effect was maximised on the current day. The relatively low temperature was responsible for 25.44% (95% CI 13.74, 33.09) of unintentional injury patients, and was associated with the number of unintentional injury patients (3114, 95% CI 1608, 4036). The relatively low temperature was associated with the excess economic burden for unintentional injury (¥197.52 million, 95% CI 102.00, 256.00; about 27.10 million dollars), accounting for 26.49% of the total economic burden. The cold temperatures generally had greater impacts on males (¥136.46 million, 95% CI 83.28, 172.42; about 18.67 million dollars) and the elderly (¥74.35 million, 95% CI 14.87, 102.14; about 10.24 million dollars).Conclusion The temperature was associated with approximately 3000 unintentional injury patients and ¥200 million (27 million dollars), accounting for 26% of the total economic burden in Tianjin, 2021.

Ureteral endometriosis accounts for about 5 % of urologic endometriosis, with a peak incidence in the age group of 30–35 years, usually with unilateral onset. Because of its insidious onset, often combined with asymptomatic loss of renal function, and the ineffectiveness of medications, surgery is the gold standard of treatment.Thus, here we report a case of ureteral endometriosis with severe hydronephrosis to raise awareness of this condition.

Purpose To assess the value of pretreatment neutrophil-to-lymphocyte ratio (NLR) and systemic immunoinflammatory index (SII) in the prognosis of nasopharyngeal carcinoma (NPC) patients. Methods This retrospective study analyzed a total of 185 NPC patients who visited the clinic from June 2015 to December 2018 and were selected as study subjects. The NLR and SII were calculated based on the collection of demographic information, clinical characteristics, and pre-treatment lymphocyte counts, neutrophil counts, and platelet counts. Predictive efficacy was evaluated using the receiver operating characteristic (ROC) curve, and survival analysis was performed through life table methods and Cox risk-proportional regression. Results Using the X-tile software, significant differences were found in clinical factors among NPC patients based on NLR (>2.91) and SII (>535.47). Age, TNM staging, SII, and NLR were identified as independent prognostic factors in a Cox regression analysis. SII had the highest area under the curve (AUC) for predicting 1-year survival, TNM staging had the highest AUC for predicting 3-year survival, and NLR had the highest AUC for predicting 5-year survival. The combined model showed superior predictive accuracy across all time points. Conclusion NLR and SII, as biomarkers of inflammation and immune status, have significant clinical applications in the prognostic assessment of NPC. The integrated prediction model combining age, TNM staging, SII, and NLR significantly improved the accuracy of survival prediction and provided a reliable basis for individualised treatment of NPC.

Abstract Background Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels. Methods We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging. Results All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed. Conclusion The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.

Abstract Steady-State Microbunching (SSMB) has been proposed as a concept to generate coherent synchrotron radiation at an electron storage ring. SSMB promises to supply kilowatt level average power radiation in the extreme ultraviolet regime, meeting the power level demands for lithography applications that presently cannot be fulfilled by established accelerator technologies. SSMB is under theoretical and experimental study, building on a proof-of-principle (PoP) experiment at the Metrology Light Source which previously showed the viability of the idea. Here we report experimental findings from systematic studies in the ongoing SSMB PoP experiment, where microbunching is generated from an energy modulation imposed by a laser of wavelength 1064 nm. The results confirm the expected dependence of the microbunching process on modulation amplitude and show that the influence of transverse-longitudinal coupling dynamics is as predicted. This confirmation of key parts of the SSMB theory establishes a solid footing for continuing the proof-of-principle efforts towards the goal of constructing a prototype SSMB light source facility.

Abstract Background Odontogenic cysts/tumor can cause severe bone destruction, which affects maxillofacial function and aesthetics. Meanwhile, metabolic reprogramming is an important hallmark of diseases. Changes in metabolic flow affect all aspects of disease, especially bone-related diseases. At present, the researches on pathogenesis of odontogenic cysts/tumor are mainly focused on the level of gene regulation, but the effects of metabolic alterations on odontogenic cysts/tumor have still underexplored. Materials and methods Imaging analysis was used to evaluate the lesion size of different odontogenic lesions. Tartrate resistant acid phosphatase (TRAP) and immunohistochemistry (IHC) assays were utilized to detect the differences in bone destruction activity in odontogenic cysts and tumors. Furthermore, metabolomics and weighted gene co-expression network analysis (WGCNA) were conducted for the metabolomic features and key metabolite screening, respectively. The effect of ferroptosis inhibition on bone destruction was confirmed by IHC, immunofluorescence, and malondialdehyde colorimetric assay. Results The bone destruction activity of ameloblastoma (AM) was the strongest and the weakest in odontogenic cysts (OC). High-throughput targeted metabolomics was used to map the metabolomic profiles of OC, odontogenic keratocyst (OKC) and AM. WGCNA and differential analysis identified L-cysteine in OKC and AM. Cystathionine γ-lyase (CTH) was further screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The functions of L-cysteine were further validated. Finally, we confirmed that CTH affected destructive activities by regulating the sensitivity of epithelial cells to ferroptosis. Conclusion High-throughput targeted metabolomics performed on diseased tissue confirmed the unique alteration of metabolic profiles in OKC and AM. CTH and its metabolite L-cysteine are the key factors regulating destructive activities.

Abstract Production of liquid fertilizers containing nitrogenous nutrients and biostimulants from sewage sludge (SS-NB) has been attracting increasing attention due to its excellent fertilization effect and resource recycling attributes. To better understand the functional effects of nutrients and biostimulants in SS-NB on soil, the adsorption capacity and mechanism of straw biochar (SB) and wood chip biochar (WCB) for alkaline and neutral SS-NB components were investigated. The adsorption of total organic carbon (TOC) from alkaline and neutral SS-NB by WCB was 61.14% and 89.73%, respectively, higher than that by SB, which was 56.25% and 83.36%. Moreover, TOC from neutral SS-NB was more readily adsorbed, especially for fulvic and humic acids. SB had a strong adsorption capacity for calcium ions and nitrogen (TKN, nitrate N, protein, amino acid) and released large amounts of P. In addition, WCB and SB showed a strong affinity for macromolecules (proteins) and reducing substances (lignin and lipids) and excellent fixation ability for phytohormones and allelochemicals. However, WCB adsorbed more types of molecular substances than SB while maintaining a high immobilization rate. Analysis of the adsorption mechanism showed that surface amino groups of the biochar were involved in adsorption, while WCB had additionally high adsorption efficiencies through pore adsorption, hydrogen bonding adsorption and pore size-exclusion effects. The study revealed that biochar can be used as an efficient adsorption carrier for SS-NB to improve soil fertility management. Graphical Abstract

Abstract Background Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. Methods The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. Results 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. Conclusions IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Due to various causes, chronic kidney disease（CKD） is characterized by chronic irreversible changes in the structure and function of kidney. The most common pathological manifestation is renal fibrosis. Many studies have demonstrated that injured renal tubular epithelial cells could release a large variety of cytokines to cause extracellular matrix deposition and promote the development of renal fibrosis during CKD. This review summarized the latest studies on the roles of renal tubular epithelial cell injury-related cytokines in CKD. It provided new concepts for clarifying the mechanism and exploring new treatments of CKD.