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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 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.

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 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.

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 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 (

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.

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.

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 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 Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients’ blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

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.

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.

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.

Agricultural non-point source pollution (ANP) had become an important source of water pollution, which seriously restricted the coordinated development of Beijing, Tianjin and Hebei. As the primary agricultural production base in the region of Beijing-Tianjin-Hebei, Hebei had serious ANP. In order to clarify the current status of ANP in Hebei and figure out the main pollution source and areas, ANP load of Hebei from 2000 to 2021 were evaluated by the export coefficient modeling (ECM) and spatial-temporal characteristics were carried out using geographic information system (GIS). In addition, ANP severity and emission characteristics of Hebei in 2021 were evaluated. The results showed that the environmental impact of ANP in southwest area was obviously more serious than that in northeast area of Hebei. Especially, ANP emissions in Hebei showed significant decreasing inflection points in 2007 and 2017, respectively, reaching a minimum by 2021. The TN and TP emissions of ANP in Hebei were 315,026.1 t and 50,323.76 t in 2021, respectively. The contribution of agricultural land, livestock and poultry breeding and rural life to TN and TP emissions were 37%, 34%, 29% and 20%, 61% and 18%, respectively. The ANP pollution mainly came from livestock and poultry breeding in Hebei Province. Based on cluster analysis, cities in Hebei were divided into four types, and the control strategies for ANP environment management were put forward.

Ulcerative colitis (UC), characterized by its recurrent nature, imposes a significant disease burden and compromises the quality of life. Emerging evidence suggests that achieving clinical remission is not sufficient for long-term remission. In pursuit of a favorable prognosis, mucosal healing (MH) has been defined as the target of therapies in UC. This paradigm shift has given rise to the formulation of diverse endoscopic and histological scoring systems, providing distinct definitions for MH. Endoscopic remission (ER) has been widely employed in clinical practice, but it is susceptible to subjective factors related to endoscopists. And there’s growing evidence that histological remission (HR) might be associated with a lower risk of disease flares, but the incorporation of HR as a routine therapeutic endpoint remains a debate. The integration of advanced technology has further enriched the definition of deep MH. Up to now, a universal standardized definition for deep MH in clinical practice is currently lacking. This review will focus on the definition of deep MH, from different dimensions, and analyze strengths and limitations, respectively. Subsequent multiple large-scale trials are needed to validate the concept of deep MH, offering valuable insights into potential benefits for UC patients.

Variable fluorescence measurements provide automatic and rapid estimates of electron-based photosynthesis. However, electron transport rates (ETR) to phytoplankton production vary greatly due to biological physiology and environmental stress along the Changjiang River to the adjacent seawater, where the turbid riverside, nutrient-rich river plume, and seawater are divided by the sediment front and plume front. We assessed the light responses of ETR, 18O-labeled gross primary production (GPP), and O2-based net community production (NCP) during the bloom season at the Changjiang River Estuary. The distribution of phytoplankton and potential photosynthesis efficiency were positively correlated, exhibiting offshore decreasing trends and peaking around the upwelling areas. The conversion factors of ΦGPP (mol e- per mol O2 production) ranged from 0.8 to 31.8, and ΦNCP ranged from 0.9 to 36.9, respectively. Φe: O increased from the nutrient-rich Changjiang diluted water (CDW) to the nutrient-poor seawater. Although ΦGPP and ΦNCP were linearly related to non-photochemical quenching (R2 > 0.5) in the CDW, this relationship was decoupled in offshore seawater due to P-limitation, light stress, and shifts in the phytoplankton community. A better relationship between ΦGPP and ΦNCP was quantified using multiple linear analyses with the light attenuation coefficient (Kd), euphotic depth (Zeu), salinity, nutrients, and temperature (p< 0.001). This improvement in accuracy represents a major step forward for widespread and accurate fluorometry-based GPP and NCP applications at high temporal and spatial resolutions in the future.