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Abstract Background This study investigated the clinical efficacy of Double INFIX for the treatment of unstable pelvic fractures. Methods We performed a retrospective analysis of 23 patients with unstable pelvic fractures treated using the Double INFIX minimally invasive technique. The cohort included five cases of Tile B1 type, eight cases of B2 type, six cases of B3 type, three cases of C1 type and one case of type C2. Pre- and postoperative evaluations included standardised pelvic serial films and three-dimensional CT scans. Key observational indicators were fracture reduction quality (assessed using Matta’s criteria), fracture healing, functional recovery (evaluated with the Majeed function assessment criteria), and incidence of complications. Results The mean follow-up duration was 24.48 ± 1.78 months. The average fracture healing time was 4.00 ± 1.41 months, and the average time for removal of fixation was 7.43 ± 1.75 months. Repeat imaging at 12 months postoperatively using Matta’s criteria showed eight cases with excellent results (52.17%), 13 cases with good results (34.78%), three cases with fair results (13.04%), and no cases with poor results. The combined excellent and good rate was 86.96%, whereas the fair rate was 13.04%. The average Majeed hip joint function score at the final follow-up was 95.04 ± 1.72. Postoperative complications included meralgia paresthetica in two cases (8.7%) and sacrococcygeal discomfort in three patients when lying flat. Conclusion Double INFIX is a minimally invasive treatment technique with adequate clinical efficacy for managing unstable pelvic fractures.

Abstract Background Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare single-gene X-linked immunodeficiency disease caused by mutations in the forkhead box protein 3 (FOXP3) gene. The typical clinical manifestations of IPEX mainly include severe atopic dermatitis, insulin-dependent type 1 diabetes mellitus, and intractable diarrhea. Case presentation Here, we report a boy with intractable diarrhea diagnosed with early-onset IPEX syndrome due to the c.434C > T (p.Ala145Val) mutation in exon 4 of the FOXP3 gene. The patient experienced intractable diarrhea and severe weight loss, and his clinical symptoms could not be alleviated by conventional supportive and anti-infection treatment. Sirolimus, an immunosuppressant, preferentially inhibits effector T cells while allowing the proliferation of Tregs and is used to treat IPEX patients and alleviate intractable diarrhea. Conclusion We reviewed the literature on the use of sirolimus for the treatment of IPEX syndrome over the past two decades.

Abstract Background This study evaluated the clinical effects of the use of a temporary bi-frame fixator in conjunction with minimally invasive percutaneous plate osteosynthesis (MIPPO) for treating AO/OTA 41B3 and 41C tibial plateau fractures (TPFs). Methods This was a retrospective analysis of 30 patients with TPFs affected by vertical compression seen from October 2019 to October 2020. All patients were treated with a bi-frame fixator to correct the vertical shortening deformity, with the MIPPO technique used after reduction. All patients underwent routine examinations at 1, 3, 6, 12 and 24months postoperatively and then annually. Clinical parameters assessed included the Hospital for Special Surgery score (HSS), number of assistants, intraoperative hemorrhage, intraoperative fluoroscopy frequency, length of hospital stay, and time to fracture healing. Radiographic findings were assessed using Rasmussen scores. Results All patients had satisfactory fracture reduction on postoperative imaging. The average operating time was 112.03 ± 20.9 min, with 15.79 ± 3.45 fluoroscopic exposures; the average blood loss was 66.63 ± 10.88 mL, the average length of hospital stay was 12.86 ± 5.11 days, and the average fracture healing time was 10.33 ± 1.48 weeks. The mean follow-up time was 23.18 ± 2.59 months. At the last follow-up, the Rasmussen anatomical score was excellent in 22 (75.3%) patients, good in 5 (16.7%), and fair in 3 (10%). The average HSS was 65.7 ± 3.26, 82.26 ± 2.28, and 87.66 ± 2.4 after 1, 6, and 12 months, respectively, and it was 92.56 ± 2.96 at the last follow-up (F = 1073.073, P

Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity, which are uniquely driven by single-atom constructs. A dramatic increase in antioxidant capacity, 158 times more than natural trolox, is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au24Cu1. Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis (OA), pH-dependent dendritic mesoporous silica nanoparticles (DMSNs) coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions, thereby enhancing the duration of effectiveness. Nonetheless, achieving high therapeutic efficacy remains a significant challenge. Herein, we describe the construction of a Clusterzymes-DMSNs-PEG complex (CDP) which remarkably diminishes reactive oxygen species (ROS) and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway. In the rabbit ACLT (anterior cruciate ligament transection) model, the CDP complex demonstrated inhibition of matrix metalloproteinase activity, preservation of type II collagen and aggregation protein secretion, thus prolonging the clusterzymes' protective influence on joint cartilage structure. Our research underscores the efficacy of the CDP complex in ROS-scavenging, enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment, leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway. This study illuminates the design, composition, and use of DMSNs and clusterzymes in biomedicine, thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.

Abstract Background Circular RNAs (circRNAs) are differentially expressed in various cardiovascular diseases, including myocardial infarction (MI) injury. However, their functional role in necroptosis-induced loss of cardiomyocytes remains unclear. We identified a cardiac necroptosis-associated circRNA transcribed from the Cacna1c gene (circCacna1c) to investigate the involvement of circRNAs in cardiomyocyte necroptosis. Methods To investigate the role of circCacna1c during oxidative stress, H9c2 cells and neonatal rat cardiomyocytes were treated with hydrogen peroxide (H2O2) to induce reactive oxygen species (ROS)-induced cardiomyocyte death. The N 6-methyladenosine (m6A) modification level of circCacna1c was determined by methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP–qPCR) analysis. Additionally, an RNA pull-down assay was performed to identify interacting proteins of circCacna1c in cardiomyocytes, and the regulatory role of circCacna1c in target protein expression was tested using a western blotting assay. Furthermore, the MI mouse model was constructed to analyze the effect of circCacna1c on heart function and cardiomyocyte necroptosis. Results The expression of circCacna1c was found to be reduced in cardiomyocytes exposed to oxidative stress and in mouse hearts injured by MI. Overexpression of circCacna1c inhibited necroptosis of cardiomyocytes induced by hydrogen peroxide and MI injury, resulting in a significant reduction in myocardial infarction size and improved cardiac function. Mechanistically, circCacna1c directly interacts with heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in the cytoplasm, preventing its nuclear translocation and leading to reduced Hnrnpf levels within the nucleus. This subsequently suppresses Hnrnpf-dependent receptor-interacting protein kinase 1 (RIPK1) expression. Furthermore, fat mass and obesity-associated protein (FTO) mediates demethylation of m6A modification on circCacna1c during necrosis and facilitates degradation of circCacna1c. Conclusion Our study demonstrates that circCacna1c can improve cardiac function following MI-induced heart injury by inhibiting the Hnrnpf/RIPK1-mediated cardiomyocyte necroptosis. Therefore, the FTO/circCacna1c/Hnrnpf/RIPK1 axis holds great potential as an effective target for attenuating cardiac injury caused by necroptosis in ischemic heart disease. Graphical Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterised by a short survival period, high malignancy, strong invasiveness, and high rates of recurrence and metastasis. Due to its unique molecular phenotype, TNBC is insensitive to endocrine therapy or molecular targeted therapy. The conventional treatment approach involves systemic chemotherapy for overall management; however, adjuvant chemotherapy after surgery has shown poor efficacy as residual lesions can easily lead to tumour recurrence. Therefore, there is an urgent need to find more effective treatment strategies. Herein, we designed a gold nanocluster coated with a metal-phenol formaldehyde network structure (AuNCs@PDA-Mn) for tumour Photothermal therapy and chemodynamic therapy (PTT and CDT), which induces systemic immune responses to suppress tumour metastasis. Experimental results show that after continuous irradiation for 10 min under an 808 nm laser (1.0W/cm2), AuNCs@PDA-Mn not only exhibits better tumour inhibition both in vitro and in vivo but also triggers stronger immune effects systemically. Therefore, this combined PTT and CDT treatment approach has great potential and provides a clinically relevant and valuable option for triple-negative breast cancer.

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

Abstract Background Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. Case presentation A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. Conclusions ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients’ pain.

Abstract Background Pulp stones are a type of pulp calcification, the presence of which tends to hinder endodontic treatment. Thus, this retrospective study aimed to analyze the distribution of pulp stones in the population in southwest China and identify the influencing factors. Materials Cone-beam computed tomography (CBCT) scans of 5066 teeth of 200 patients (91 males and 109 females) aged 16–45 years were evaluated. Pulp stones were marked as either present or absent when distinct radiopaque masses were found in the pulp cavity, then evaluated the occurrence of pulp stones with regard to tooth type, sex, age group, and contact it with tooth status. The Pearson chi-square test and nonparametric test were used for statistical analysis. Results Pulp stones were detected in 49.0% of patients and 7.4% of teeth, respectively. The incidence in females was 1.9 times higher than in males (OR = 1.9, 95% CI = 1.1–3.3, p = 0.001). Pulp stones were most prevalent in patients 36–45 years of age. Furthermore, in the age range of 16–45 years, the likelihood of finding pulp stones increased 1.1 times per year with age (OR = 1.1, 95% CI = 1.0–1.1, p = 0.032). A higher incidence of pulp stones was observed in the maxilla and molars. Of the 5066 teeth studied, pulp stones were more common in non-intact teeth. Conclusion Nearly half of the population in southwest China had pulp stones. Pulp stones were found significantly more often in females, maxilla, and non-intact teeth, and their frequency increased with age. For dentists, understanding the distribution of pulp stones is crucial for the proper design of root canal treatment (RCT). Trial registration This study was approved by the Ethics Committee of the Affiliated Hospital of Stomatology, Southwest Medical University (certificate number: 20220818001).

Hydrogel is an interesting topic in polymer chemistry, which is closely related to daily life and advanced technology. In this paper, we report an activity to deliver hydrogel chemistry into middle school classrooms by undergraduates as a bridge between professors and students. During the activity, undergraduates act as a bridge to receive knowledge from professors, reprocess it, and finally deliver it to middle school students. The activity comprises a 60 min lecture and a 30 min hands-on experiment and aims to provide a deep understanding of hydrogel. The lecture starts from the jelly, a popular snack for students, in order to introduce hydrogels. Then, the various applications of hydrogels are mentioned to indicate why hydrogel materials are interesting and how hydrogel materials help doctors treat various diseases. Moreover, middle school students expand their minds from everyday applications to advanced technologies by engaging in discussions as well as a hands-on experiment. The survey before and after the activity shows it can play an important role in helping middle school students understand hydrogels and sprout their interest in chemistry. The activity has been successfully held in four local middle schools and more sessions are planned to be held in more middle schools in the near future. Undergraduates also deepened their understanding of hydrogel chemistry and sprouted their interest in scientific research in this activity.

This paper proposes a novel phase-based short-term traffic flow prediction method based on parallel multi-task learning for isolated intersections. Different from traditional short-term traffic flow prediction methods, we take the traffic flow of each phase as the minimum prediction unit, instead of directly utilising the traffic flow of a single lane with large random fluctuations. Meanwhile, we design a novel encoding and decoding structure whereby external influencing factors have been incorporated both into encoding and decoding operations. Furthermore, a fusion strategy is proposed to predict the traffic flow of each phase by integrating the traffic flows of lanes whose right of way are provided by the phase. In the fusion strategy, we develop a parallel multi-task prediction framework whereby a new loss function is defined to improve the prediction accuracy. Finally, the proposed method is tested with the traffic flow data collected from an intersection of South Changsheng Road located in the city of Jiaxing. The findings illustrate that the proposed method can achieve better prediction results at different sampling time scales, compared to the existing short-term traffic flow prediction methods.

ObjectiveThe objective of the study was to investigate the application effect of scenario simulation teaching based on the Mini-Clinical Evaluation Exercise (Mini-CEX) and direct observation of procedural skills (DOPS) rating scales in urology clinical apprenticeship training.Materials and methodsA total of 32 students from the class of 2015–2017 who completed their traineeship in the Department of Urology of our hospital were selected and divided into a research group and a routine group. Routine teaching was implemented for the trainees in the control group, while situational simulation teaching based on the Mini-CEX and DOPS scoring scales was implemented for the trainees in the research group. The Mini-CEX and DOPS scores and student satisfaction were compared at the time of admission and discharge between the two groups.ResultsAt the time of admission, there was no statistically significant difference between the Mini-CEX and DOPS scores of the two groups of trainees (p > 0.05). However, at the time of discharge, the Mini-CEX and DOPS scores of the trainees in the study group were 53.21 ± 4.52 and 81.23 ± 3.57, respectively, which were significantly higher than those in the conventional group (p

Background Fagopyrum dibotrys is an important wild food and feed germplasm resource. It has high nutritional and medicinal value and is rich in natural products, including flavonoids, phenolic acids, coumarins, and alkaloids. Endophytic fungi in F. dibotrys have emerged as valuable sources of natural products. However, studies on the biological activity and chemical composition of these endophytic fungi remain limited. Methods In this paper, a new method to obtain natural active ingredients by fermentation of endophytic fungi from medicinal plants was proposed. Then the antioxidant and pathogenic activities of the endophytic fungi extracts were determined in vitro. In addition, secondary metabolites produced by endophytic fungi with medicinal activity were analyzed by high performance liquid chromatography-tandem mass spectrometry (LC-MS). Results Among the 95 endophytic fungal strains in F. dibotrys, four strains with high phenol yields were selected by reaction: Alternaria alstroemeriae (J2), Fusarium oxysporum (J15), Colletotrichum karsti (J74), and Colletotrichum boninense (J61). Compared with those of various extracts, the ethyl acetate fractions of A. alstroemeriae (J2), F. oxysporum (J15), and C. boninense (J61) exhibited superior antioxidant and antibacterial properties. The results indicated that the fungal extract was an excellent natural antioxidant and might be a potential antibacterial agent. The DPPH free radical clearance of A. alstroemeriae was 94.96 ± 0.004%. These findings indicated that A. alstroemeriae had strong antioxidant activity. In addition, the extract of A. alstroemeriae had good antibacterial activity against Escherichia coli and Staphylococcus aureus, with MICs of 0.5 and 0.05 mg/mL, respectively. The chemical constituents of the ethyl acetate extract from A. alstroemeriae were further analyzed by liquid chromatography–mass spectrometry (LC–MS). We noted that A. alstroemeriae can create a variety of medicinal substances that have high value in medicine, such as caffeic acid (884.75 ng/mL), 3-phenyllactic acid (240.72 ng/mL) and norlichexanthone (74.36 ng/mL). Discussion In summary, many valuable active substances and medicinal substances can be obtained through the study of endophytic fungi of F. dibotrys.

Bone metastasis is a debilitating complication that frequently occurs in the advanced stages of breast cancer. However, the underlying molecular and cellular mechanisms of the bone metastasis remain unclear. Here, we elucidate how bone metastasis arises from tumor cells that detach from the primary lesions and infiltrate into the surrounding tissue, as well as how these cells disseminate to distant sites. Specifically, we elaborate how tumor cells preferentially grow within the bone micro-environment and interact with bone cells to facilitate bone destruction, characterized as osteoclastic bone metastasis, as well as new bone matrix deposition, characterized as osteoblastic bone metastasis. We also updated the current understanding of the molecular mechanisms underlying bone metastasis and reasons for relapse in breast cancer, and also opportunities of developing novel diagnostic approaches and treatment.

Abstract In order to predict the damage behaviours of 3D-printed continuous carbon fibre (CCF) reinforced composites, when additional short carbon fibre (SCF) composite components are employed for continuous printing or special functionality, a novel path-dependent progressive failure (PDPF) numerical approach is developed. First, a progressive failure model using Hashin failure criteria with continuum damage mechanics to account for the damage initiation and evaluation of 3D-printed CCF reinforced polyamide (PA) composites is developed, based on actual fibre placement trajectories with physical measurements of 3D-printed CCF/PA constituents. Meanwhile, an elastic-plastic model is employed to predict the plastic damage behaviours of SCF/PA parts. Then, the accuracy of the PDPF model was validated so as to study 3D-printed CCF/PA composites with either negative Poisson’s ratio or high stiffness. The results demonstrate that the proposed PDPF model can achieve higher prediction accuracies in mechanical properties of these 3D-printed CCF/PA composites. Mechanism analyses show that the stress distribution is generally aggregated in the CCF areas along the fibre placement paths, and the shear damage and matrix tensile/compressive damage are the key damage modes. This study provides a new approach with valuable information for characterising complex 3D-printed continuous fibre-matrix composites with variable mechanical properties and multiple constituents.

Traffic signal control (TSC) plays a crucial role in enhancing traffic capacity. In recent years, researchers have demonstrated improved performance by utilizing deep reinforcement learning (DRL) for optimizing TSC. However, existing DRL frameworks predominantly rely on manually crafted states, actions, and reward designs, which limit direct information exchange between the DRL agent and the environment. To overcome this challenge, we propose a novel design method that maintains consistency among states, actions, and rewards, named uniformity state-action-reward (USAR) method for TSC. The USAR method relies on: 1) Updating the action selection for the next time step using a formula based on the state perceived by the agent at the current time step, thereby encouraging rapid convergence to the optimal strategy from state perception to action; and 2) integrating the state representation with the reward function design, allowing for precise assessment of the efficacy of past action strategies based on the received feedback rewards. The consistency-preserving design method jointly optimizes the TSC strategy through the updates and feedback among the Markov elements. Furthermore, the method proposed in this paper employs a residual block into the DRL model. It introduces an additional pathway between the input and output layers to transfer feature information, thus promoting the flow of information across different network layers. To assess the effectiveness of our approach, we conducted a series of simulation experiments using the simulation of urban mobility. The USAR method, incorporating a residual block, outperformed other methods and exhibited the best performance in several evaluation metrics.

Objective Based on the basic functions of ATO (automatic train operation) and TCMS (train control and monitoring system), adopting an integrated design approach can simplify repititive designs and optimize train control functions, thus it is necessary to carry out relevant research. Method By comprehensively analyzing the functions and applications of ATO and TCMS in urban rail transit at the present stage, the integration of ATO and TCMS control functions is studied. A design scheme for integrated train systems with improved control functions is proposed, and the advantages brought by functional integration are analyzed. Result & Conclusion After integrating ATO and TCMS functions, the system integration of trains can be enhanced, making it easier to achieve intelligence. However, challenges in technology and management need to be overcome.

As major forming elements of γ′ strengthening phase, Al and Ti are critical for achieving superior properties of Ni-based superalloy. However, Al + Ti over 6 wt% leads to poor printability and cracking during additive manufacturing. In this work, the printability and properties of a nickel-based superalloy with Al + Ti reaching 7 wt% is synchronously improved via alloying minor Sc, the mechanism behind that is revealed by investigating the effects of Sc on the grain size, precipitation, and tensile fracture behavior of that nickel-based superalloy. This work provides a promising alternative method for optimizing the performance of superalloys prepared by additive manufacturing.

0Cr16Ni5Mo1 super martensitic stainless steel has excellent weldability and is an economical material with a high life cycle and low cost, but there are few researches and applications of this material in additive manufacturing. In order to realize the application of 0Cr16Ni5Mo1 large-area laser cladding technology, the multi-track lap cladding of the material was studied. In this work, a multi-physical finite element model of multi-layer multi-track laser cladding was established, taking into account thermodynamic processes such as phase transition, Marangoni convection, and buoyancy. The flow and heat transfer behavior of 0Cr16Ni5Mo1 in multi-layer multi-track laser cladding process and the characteristics of the molten pool are studied. The research focused on the flow heat transfer behavior and molten pool characteristics of 0Cr16Ni5Mo1 during multi-layer multi-track laser cladding. The discussed aspects include the evolution history of the temperature field within the molten pool, flow field characteristics, molten pool dimensions, and dilution ratio under various laser powers and overlap rates. The results show that with the increase of overlap rate, the morphology of molten pools in different clad tracks will also change, and the flow rate, dilution ratio, and length of molten pools in the second track are negatively correlated, while the temperature and height of molten pools are positively correlated. As the laser power increases, all the characteristic quantities are positively correlated with it.