This study aims to understand the biological characteristics of Streptococcus dysgalacti-ae of yak origin.Bacterial isolation and identification,drug susceptibility test,virulence gene test and pathogenicity test were carried out on milk samples of yaks from Naqu City to evaluate the bi-ological characteristics of the isolated strains.Meanwhile,molecular biological information such as virulence factors and drug resistance genes were analyzed by whole genome sequencing,and viru-lence genes were verified by PCR.The results showed that a strain of Streptococcus dysgalactiae was isolated from the milk of yak,and its colony morphology was pinpoint size,smooth edge and milky white.This strain is sensitive to many antibiotics(penicillin G,cephalosporin,ciprofloxacin,tetracycline,erythromycin,etc.).Virulence gene test results showed that the strain carries six key virulence genes(cyl,eno,scpB,bca,bac and napr),which may be closely related to its pathoge-nicity.In the pathogenicity test,the mice were listless and less active after infection,but no death occurred during the observation period.The pathological changes of spleen,kidney,liver and lung tissue were found,suggesting that the strain had certain pathogenic potential but not high lethali-ty.Whole genome sequencing data showed that the gene length of this strain was 4 079 280 bp,the GC content was 39.41％,3 964 coding genes were predicted,604 of which were annotated as viru-lence factors,and another 28 gene mutations may enhance its pathogenic ability.Through annota-tion of CARD database,two Pat A resistance genes and two lmrp resistance genes were found,re-vealing their potential resistance mechanism.Through whole genome sequencing technology and bioinformatics analysis method,this study revealed the genomic characteristics,drug resistance and pathogenicity mechanism of Streptococcus dysgalactiae of yak origin.The findings provide impor-tant scientific evidence for further exploration of the pathogenicity,drug resistance mechanisms,and molecular evolution of yak-derived Streptococcus agalactiae.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:This study used data-independent acquisition (DIA) proteomics to analyze plasma protein expression in sepsis-induced coagulopathy (SIC), identify key biomarkers, and develop a diagnostic model.Methods:This prospective study included 46 adult sepsis patients from the intensive care unit. Patients were categorized into a general sepsis group ( n=26) and an SIC group ( n=20) based on established SIC criteria. Plasma samples underwent proteomic and bioinformatics analyses to identify differentially expressed protein (DEP) using LASSO regression and Random Forest. A diagnostic model was constructed and assessed via receiver operating characteristic (ROC) curve analysis. Results:The baseline data revealed that SIC patients exhibited longer prothrombin times, lower platelet counts, and higher D-dimer, fibrin degradation products, blood lactate, SOFA scores, and APACHE Ⅱ scores compared with general sepsis patients ( P<0.05). DIA proteomics identified 2 637 proteins, with 240 DEP meeting the criteria (fold change >1.5, P<0.05), including 81 upregulated and 159 downregulated DEP. Subcellular localization analysis revealed that DEPs were predominantly extracellular and nuclear. Gene ontology (GO) annotation showed that DEP were mainly involved in cellular physiology, biological regulation, and stress response processes in biological processes. Domain annotation revealed a predominance of immunoglobulin V regions in DEP, which are crucial for antigen recognition and binding. KEGG enrichment analysis showed significant enrichment of DEP in pathways related to natural killer cell-mediated cytotoxicity, glycosylphosphatidylinositol anchor biosynthesis, tumor necrosis factor signaling, and NF-κB signaling. LASSO regression identified angiogenin and C-type lectin domain family 10 member A as key DEP. The SIC diagnostic nomogram showed an area under the curve of 0.896, with 0.731 specificity and 0.900 sensitivity. Conclusion:The nomogram incorporating angiogenin and C-type lectin domain family 10 member A provides an accurate tool for SIC diagnosis.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

This study aims to understand the biological characteristics of Streptococcus dysgalacti-ae of yak origin.Bacterial isolation and identification,drug susceptibility test,virulence gene test and pathogenicity test were carried out on milk samples of yaks from Naqu City to evaluate the bi-ological characteristics of the isolated strains.Meanwhile,molecular biological information such as virulence factors and drug resistance genes were analyzed by whole genome sequencing,and viru-lence genes were verified by PCR.The results showed that a strain of Streptococcus dysgalactiae was isolated from the milk of yak,and its colony morphology was pinpoint size,smooth edge and milky white.This strain is sensitive to many antibiotics(penicillin G,cephalosporin,ciprofloxacin,tetracycline,erythromycin,etc.).Virulence gene test results showed that the strain carries six key virulence genes(cyl,eno,scpB,bca,bac and napr),which may be closely related to its pathoge-nicity.In the pathogenicity test,the mice were listless and less active after infection,but no death occurred during the observation period.The pathological changes of spleen,kidney,liver and lung tissue were found,suggesting that the strain had certain pathogenic potential but not high lethali-ty.Whole genome sequencing data showed that the gene length of this strain was 4 079 280 bp,the GC content was 39.41％,3 964 coding genes were predicted,604 of which were annotated as viru-lence factors,and another 28 gene mutations may enhance its pathogenic ability.Through annota-tion of CARD database,two Pat A resistance genes and two lmrp resistance genes were found,re-vealing their potential resistance mechanism.Through whole genome sequencing technology and bioinformatics analysis method,this study revealed the genomic characteristics,drug resistance and pathogenicity mechanism of Streptococcus dysgalactiae of yak origin.The findings provide impor-tant scientific evidence for further exploration of the pathogenicity,drug resistance mechanisms,and molecular evolution of yak-derived Streptococcus agalactiae.

Objective:This study used data-independent acquisition (DIA) proteomics to analyze plasma protein expression in sepsis-induced coagulopathy (SIC), identify key biomarkers, and develop a diagnostic model.Methods:This prospective study included 46 adult sepsis patients from the intensive care unit. Patients were categorized into a general sepsis group ( n=26) and an SIC group ( n=20) based on established SIC criteria. Plasma samples underwent proteomic and bioinformatics analyses to identify differentially expressed protein (DEP) using LASSO regression and Random Forest. A diagnostic model was constructed and assessed via receiver operating characteristic (ROC) curve analysis. Results:The baseline data revealed that SIC patients exhibited longer prothrombin times, lower platelet counts, and higher D-dimer, fibrin degradation products, blood lactate, SOFA scores, and APACHE Ⅱ scores compared with general sepsis patients ( P<0.05). DIA proteomics identified 2 637 proteins, with 240 DEP meeting the criteria (fold change >1.5, P<0.05), including 81 upregulated and 159 downregulated DEP. Subcellular localization analysis revealed that DEPs were predominantly extracellular and nuclear. Gene ontology (GO) annotation showed that DEP were mainly involved in cellular physiology, biological regulation, and stress response processes in biological processes. Domain annotation revealed a predominance of immunoglobulin V regions in DEP, which are crucial for antigen recognition and binding. KEGG enrichment analysis showed significant enrichment of DEP in pathways related to natural killer cell-mediated cytotoxicity, glycosylphosphatidylinositol anchor biosynthesis, tumor necrosis factor signaling, and NF-κB signaling. LASSO regression identified angiogenin and C-type lectin domain family 10 member A as key DEP. The SIC diagnostic nomogram showed an area under the curve of 0.896, with 0.731 specificity and 0.900 sensitivity. Conclusion:The nomogram incorporating angiogenin and C-type lectin domain family 10 member A provides an accurate tool for SIC diagnosis.

Objective:To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis.Methods:A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People′s Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up.Results:Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott′s methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function.Conclusions:For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-transplantation pathological assessment for individualized treatment.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.