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BackgroundThoracoscopic surgery is a primary treatment for lung cancer, with lobectomy and mediastinal lymph node dissection being the predominant surgical approaches for invasive lung cancer. While many thoracic surgeons can proficiently perform lobectomy, thorough and standardized lymph node dissection remains challenging. This study aimed to explore a safer and more efficient surgical method for mediastinal lymph node dissection in lung cancer.MethodsA prospective randomized controlled study was conducted, involving 100 patients with right lung cancer who were admitted to our hospital from January 2021 to April 2024 and met the inclusion criteria. These patients were randomly divided into an observation group (tissue pneumoperitoneum technique around lymph nodes group) and a control group (conventional surgery group). Thoracoscopic lobectomy and mediastinal lymph node dissection were performed. Intraoperative and postoperative related indicators were observed to validate the effectiveness and safety of the tissue pneumoperitoneum technique around lymph nodes.ResultsThe observation group showed a significantly shorter lymph node dissection surgery time compared to the control group, with a statistically significant difference (p < 0.05). The number of lymph nodes dissected in the observation group was significantly higher than that in the control group, with a statistically significant difference (p < 0.05). Although the observation group had slightly more mediastinal lymph node stations dissected than the control group, the difference was not statistically significant (p > 0.05). The total drainage volume within three days postoperatively was comparable between the two groups, with no statistically significant difference (p > 0.05). The observation group had shorter chest tube indwelling time and postoperative hospital stay than the control group, with statistically significant differences (p < 0.05). The incidence of surgical complications was similar between the two groups, and there were no perioperative deaths.ConclusionThe tissue pneumoperitoneum technique around lymph nodes is a more efficient method for mediastinal lymph node dissection in lung cancer, demonstrating safety and feasibility, and is worthy of promotion.

Network traffic state prediction has been constantly challenged by complex spatiotemporal features of traffic information as well as imperfection in streaming data. This paper proposes a traffic flow prediction model for spatiotemporal graph networks based on fusion of attention mechanisms (STGNN-FAM) to simultaneously tackle these challenges. This model contains a spatial feature extraction layer, a bidirectional temporal feature extraction layer, and an attention fusion layer, which not only fully considers the temporal and spatial features of the traffic flow problem but also uses the attention mechanism to enhance the critical temporal and spatial features to achieve more accurate and robust predictions. Experimental results on a network traffic speed dataset PeMSD7 show that the proposed STGNN-FAM outperforms several important benchmarks in prediction accuracy and the ability to withstand interference in the data stream, especially for mid- and long-term prediction of 30 minutes and 45 minutes.

Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment.Methods: HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were exposed to various concentrations of silibinin for indicated times. Cell viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was determined through the use of colony formation and 5-Ethynyl-2′- deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining assay and flow cytometry (FCM). The protein levels of extracellular regulated protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through western blotting (WB). Mitochondrial membrane potential changes were determined via 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1). A cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor activity of silibinin in vivo.Results: Inhibition of the ERK protein by silibinin led to a significant decrease in mitochondrial membrane potential, which, in turn, caused Cytochrome C to be released from the mitochondria. The activation of downstream apoptotic pathways led to apoptosis of cholangiocarcinoma cells. In general, silibinin inhibited the growth of cholangiocarcinoma cell line xenograft tumors.Conclusions: Silibinin is able to inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma treatment.

Scene sonification is a powerful technique to help Visually Impaired People (VIP) understand their surroundings. Existing methods usually perform sonification on the entire images of the surrounding scene acquired by a standard camera or on the priori static obstacles acquired by image processing algorithms on the RGB image of the surrounding scene. However, if all the information in the scene are delivered to VIP simultaneously, it will cause information redundancy. In fact, biological vision is more sensitive to moving objects in the scene than static objects, which is also the original intention of the event-based camera. In this paper, we propose a real-time sonification framework to help VIP understand the moving objects in the scene. First, we capture the events in the scene using an event-based camera and cluster them into multiple moving objects without relying on any prior knowledge. Then, sonification based on MIDI is enabled on these objects synchronously. Finally, we conduct comprehensive experiments on the scene video with sonification audio attended by 20 VIP and 20 Sighted People (SP). The results show that our method allows both participants to clearly distinguish the number, size, motion speed, and motion trajectories of multiple objects. The results show that our method is more comfortable to hear than existing methods in terms of aesthetics.

In order to help visually impaired people to avoid obstacles, a K-band millimetre wave (MMW) radar system based on the principle of frequency-modulated continuous wave (FMCW) is proposed in this study. The FMCW basic principle and the signal processing algorithm are elaborated in detail. The prototype of the radar system has been designed and manufactured. The experiment results show the qualified detection accuracy in view of low deviation. The maximum deviations from the range measurement experiments for a person and a car are 0.14 and 0.47 m, respectively. As a wearable system, the radar system has the characteristics of low power and small size, which is very suitable for blind navigation application. In addition, the MMW radar has broad application prospects in the field of automotive blind spot detection and small robots.

In recent years, with the development of depth cameras and scene detection algorithms, a wide variety of electronic travel aids for visually impaired people have been proposed. However, it is still challenging to convey scene information to visually impaired people efficiently. In this paper, we propose three different auditory-based interaction methods, i.e., depth image sonification, obstacle sonification as well as path sonification, which convey raw depth images, obstacle information and path information respectively to visually impaired people. Three sonification methods are compared comprehensively through a field experiment attended by twelve visually impaired participants. The results show that the sonification of high-level scene information, such as the direction of pathway, is easier to learn and adapt, and is more suitable for point-to-point navigation. In contrast, through the sonification of low-level scene information, such as raw depth images, visually impaired people can understand the surrounding environment more comprehensively. Furthermore, there is no interaction method that is best suited for all participants in the experiment, and visually impaired individuals need a period of time to find the most suitable interaction method. Our findings highlight the features and the differences of three scene detection algorithms and the corresponding sonification methods. The results provide insights into the design of electronic travel aids, and the conclusions can also be applied in other fields, such as the sound feedback of virtual reality applications.

Navigational assistance aims to help visually-impaired people to ambulate the environment safely and independently. This topic becomes challenging as it requires detecting a wide variety of scenes to provide higher level assistive awareness. Vision-based technologies with monocular detectors or depth sensors have sprung up within several years of research. These separate approaches have achieved remarkable results with relatively low processing time and have improved the mobility of impaired people to a large extent. However, running all detectors jointly increases the latency and burdens the computational resources. In this paper, we put forward seizing pixel-wise semantic segmentation to cover navigation-related perception needs in a unified way. This is critical not only for the terrain awareness regarding traversable areas, sidewalks, stairs and water hazards, but also for the avoidance of short-range obstacles, fast-approaching pedestrians and vehicles. The core of our unification proposal is a deep architecture, aimed at attaining efficient semantic understanding. We have integrated the approach in a wearable navigation system by incorporating robust depth segmentation. A comprehensive set of experiments prove the qualified accuracy over state-of-the-art methods while maintaining real-time speed. We also present a closed-loop field test involving real visually-impaired users, demonstrating the effectivity and versatility of the assistive framework.

The use of RGB-Depth (RGB-D) sensors for assisting visually impaired people (VIP) has been widely reported as they offer portability, function-diversity and cost-effectiveness. However, polarization cues to assist traversability awareness without precautions against stepping into water areas are weak. In this paper, a polarized RGB-Depth (pRGB-D) framework is proposed to detect traversable area and water hazards simultaneously with polarization-color-depth-attitude information to enhance safety during navigation. The approach has been tested on a pRGB-D dataset, which is built for tuning parameters and evaluating the performance. Moreover, the approach has been integrated into a wearable prototype which generates a stereo sound feedback to guide visually impaired people (VIP) follow the prioritized direction to avoid obstacles and water hazards. Furthermore, a preliminary study with ten blindfolded participants suggests its effectivity and reliability.

The introduction of RGB-Depth (RGB-D) sensors into the visually impaired people (VIP)-assisting area has stirred great interest of many researchers. However, the detection range of RGB-D sensors is limited by narrow depth field angle and sparse depth map in the distance, which hampers broader and longer traversability awareness. This paper proposes an effective approach to expand the detection of traversable area based on a RGB-D sensor, the Intel RealSense R200, which is compatible with both indoor and outdoor environments. The depth image of RealSense is enhanced with IR image large-scale matching and RGB image-guided filtering. Traversable area is obtained with RANdom SAmple Consensus (RANSAC) segmentation and surface normal vector estimation, preliminarily. A seeded growing region algorithm, combining the depth image and RGB image, enlarges the preliminary traversable area greatly. This is critical not only for avoiding close obstacles, but also for allowing superior path planning on navigation. The proposed approach has been tested on a score of indoor and outdoor scenarios. Moreover, the approach has been integrated into an assistance system, which consists of a wearable prototype and an audio interface. Furthermore, the presented approach has been proved to be useful and reliable by a field test with eight visually impaired volunteers.

Abstract Porcine epidemic diarrhea virus (PEDV) has emerged in American countries, and it has reemerged in Asia and Europe, causing significant economic losses to the pig industry worldwide. In the present study, the 17GXCZ-1ORF3d strain, which has a naturally large deletion at the 172–554 bp position of the ORF3 gene, together with the 17GXCZ-1ORF3c strain, was serially propagated in Vero cells for up to 120 passages. The adaptability of the two strains gradually increased through serial passages in vitro. Genetic variation analysis of the variants of the two strains from different generations revealed that the naturally truncated ORF3 gene in the 17GXCZ-1ORF3d variants was stably inherited. Furthermore, the survival, viral shedding and histopathological lesions following inoculation of piglets demonstrated that the virulence of 17GXCZ-1ORF3d-P120 was significantly attenuated. These results indicate that the naturally truncated ORF3 gene may accelerate the attenuation of virulence and is involved in PEDV virulence together with mutations in other structural genes. Importantly, immunization of sows with G2b 17GXCZ-1ORF3d-P120 increased PEDV-specific IgG and IgA antibody levels in piglets and conferred partial passive protection against heterologous G2a PEDV strains. Our findings suggest that an attenuated strain with a truncated ORF3 gene may be a promising candidate for protection against PEDV.

Abstract Recently, multi-modal vision-language foundation models have gained significant attention in the medical field. While these models offer great opportunities, they still face crucial challenges, such as the requirement for fine-grained knowledge understanding in computer-aided diagnosis and the capability of utilizing very limited or even no task-specific labeled data in real-world clinical applications. In this study, we present MaCo, a masked contrastive chest X-ray foundation model that tackles these challenges. MaCo explores masked contrastive learning to simultaneously achieve fine-grained image understanding and zero-shot learning for a variety of medical imaging tasks. It designs a correlation weighting mechanism to adjust the correlation between masked chest X-ray image patches and their corresponding reports, thereby enhancing the model’s representation learning capabilities. To evaluate the performance of MaCo, we conducted extensive experiments using 6 well-known open-source X-ray datasets. The experimental results demonstrate the superiority of MaCo over 10 state-of-the-art approaches across tasks such as classification, segmentation, detection, and phrase grounding. These findings highlight the significant potential of MaCo in advancing a wide range of medical image analysis tasks.

Background: COVID-19 patients exhibit higher incidence of thrombosis in arteries and veins, including those in lungs. Vasa vasorum, which support large blood vessels, have shown involvement in these pathologic processes. Methods: To further explore the extent of microvascular damage caused by COVID-19 infection, we examined resected main, right, or left pulmonary artery specimens from patients undergoing bilateral lung transplantation for COVID-19– or non–COVID-19–induced pulmonary fibrosis compared with organ donors by histologic and immunohistologic analyses. Results: Vasa vasorum density was found to be higher in specimens procured from patients with COVID-19 and associated with pulmonary artery hypertension compared with lung transplant donors. In addition, we found immunothrombosis within vasa vasorum in specimens from COVID-19 patients with more immune infiltration, including CD15+, CD44+, and CD68+ cells. Conclusions: These findings reveal that COVID-19 affects the vasa vasorum of pulmonary arteries and suggest that infection may lead to large-vessel dysfunction and organ failure.

Abstract Background Chronic inflammation contributes to the progression of isoproterenol (ISO)‐induced heart failure (HF). Caspase‐associated recruitment domain (CARD) families are crucial proteins for initiation of inflammation in innate immunity. Nonetheless, the relevance of CARDs in ISO‐driven cardiac remodelling is little explored. Methods This study utilized Card9−/− mice and reconstituted C57BL/6 mice with either Card9−/− or Otud1−/− marrow‐derived cells. Mechanistic studies were conducted in primary macrophages, cardiomyocytes, fibroblasts and HEK‐293T cells. Results Here, we demonstrated that CARD9 was substantially upregulated in murine hearts infused with ISO. Either whole‐body CARD9 knockout or myeloid‐specific CARD9 deletion inhibited ISO‐driven murine cardiac inflammation, remodelling and dysfunction. CARD9 deficiency in macrophages prevented ISO‐induced inflammation and alleviated remodelling changes in cardiomyocytes and fibroblasts. Mechanistically, we found that ISO enhances the activity of CARD9 by upregulating ovarian tumour deubiquitinase 1 (OTUD1) in macrophages. We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33‐linked ubiquitin from CARD9 to promote the assembly of the CARD9‐BCL10‐MALT1 (CBM) complex, without affecting CARD9 stability. The ISO‐activated CBM complex results in NF‐κB activation and macrophage‐based inflammatory gene overproduction, which then enhances cardiomyocyte hypertrophy and fibroblast fibrosis, respectively. Myeloid‐specific OTUD1 deletion also attenuated ISO‐induced murine cardiac inflammation and remodelling. Conclusions These results suggested that the OTUD1‐CARD9 axis is a new pro‐inflammatory signal in ISO‐challenged macrophages and targeting this axis has a protective effect against ISO‐induced HF. Key points Macrophage CARD9 was elevated in heart tissues of mice under chronic ISO administration. Either whole‐body CARD9 knockout or myeloid‐specific CARD9 deficiency protected mice from ISO‐induced inflammatory heart remodeling. ISO promoted the assembly of CBM complex and then activated NF‐κB signaling in macrophages through OTUD1‐mediated deubiquitinating modification. OTUD1 deletion in myeloid cells protected hearts from ISO‐induced injuries in mice.

Introduction: Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development. Objectives: To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features. Methods: LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells. Results: Results demonstrated that tree shrews exhibited an average survival time of 3–5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO2 to FiO2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS. Conclusion: This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-β in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.

ABSTRACTInfluenza A viruses (IAVs) pose a persistent potential threat to human health because of the spillover from avian and swine infections. Extensive surveillance was performed in 12 cities of Guangxi, China, during 2018 and 2023. A total of 2540 samples (including 2353 nasal swabs and 187 lung tissues) were collected from 18 pig farms with outbreaks of respiratory disease. From these, 192 IAV-positive samples and 19 genomic sequences were obtained. We found that the H1 and H3 swine influenza A viruses (swIAVs) of multiple lineages and genotypes have continued to co-circulate during that time in this region. Genomic analysis revealed the Eurasian avian-like H1N1 swIAVs (G4) still remained predominant in pig populations. Strikingly, the novel multiple H3N2 genotypes were found to have been generated through the repeated introduction of the early H3N2 North American triple reassortant viruses (TR H3N2 lineage) that emerged in USA and Canada in 1998 and 2005, respectively. Notably, when the matrix gene segment derived from the H9N2 avian influenza virus was introduced into endemic swIAVs, this produced a novel quadruple reassortant H1N2 swIAV that could pose a potential risk for zoonotic infection.

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus’s titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Abstract Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6–7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9–64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals.