Objective To establish a model that integrates ultrasound features and immunological characteristics for predicting the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer patients.Methods A total of 203 breast cancer patients undergoing preoperative NAC at the Fifth Medical Center of the PLA General Hospital between July 2021 and July 2024 were screened.In line with the inclusion/exclusion criteria,177 patients were included.Data on ultrasound and immunohistochemistry was collected.These patients were divided into pathological complete response(pCR)and non-pathological complete response(non-pCR)groups based on postoperative pathology.Factors with P＜0.0 1 in univariate analysis were evaluated using multivariate Logistic regression.Independent predictive factors were used to construct and validate the ultrasound-immunohistochemical model via Bootstrap.Results The reduction rateof the maximum diameter of lesions,posterior echo attenuation,PR status and HER-2 status were identified as independent predictors of pCR(all P＜0.05).The model proved to be highly accurate and stable.Conclusion The model that combines ultrasound and immunohistochemical features can effectively evaluatep CR after NAC in breast cancer patients.

Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

OBJECTIVE To investigate of the regulatory effects of Budi Shenlian Recipe on gut microbiota and the phenotypic transition of tumor-associated macrophages(TAMs)in colorectal cancer(CRC)mice.METHODS Forty male BALB/c mice were divided into blank control group,model group,positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group(n=8).CRC-bearing models were established by subcutaneous injection of CT26 cells.Additionally,10 male BALB/c mice were divided into the Budi Shenlian Recipe fecal microbiota transplantation(BFMT)group and model fecal microbiota transplantation(MFMT)group(n=5).The gut microbiota of these mice was cleared using a mixed solution of quadruple antibiotics,followed by subcutaneous injection of CT26 cells to construct pseudo-germ-free CRC-bearing mice.Fecal samples from the model group and high-dose Budi Shenlian Recipe group were collected to prepare fecal microbiota solutions.The BFMT group received gavage with fecal microbiota solution from the high-dose Budi Shenlian Recipe group,while the MFMT group received gavage with fecal micro-biota solution from the model group.Tumor volume changes were observed and recorded.HE staining was used to assess pathological changes in tumor tissues.16S sequencing was performed to analyze changes in gut microbiota.Flow cytometry and immunofluorescence staining were used to evaluate the proportion of M1/M2 type TAMs in tumor tissues.ELISA was used to detect differences in TNF-α and IL-10 levels in tumor tissues.RESULTS Compared to the model group,the tumor volume of mice in the positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group grew more slowly(P<0.01).HE staining showed necrotic areas in tumor tissues and reduced mitotic figures in the positive control and Budi Shenlian Recipe groups compared to the model group.16S rRNA sequencing showed no significant differences in Chao1 and ACE indices between the high-dose Budi Shenlian Recipe group and the model group.PCoA analysis indicated a distinct microbial community structure between the blank group and mod-el group,with the microbial structure of CRC mice in the Budi Shenlian Recipe group closer to that of the blank group.Compared to the blank group,the model group showed a significant decrease in the proportion of Muribaculaceae,Muribaculum,Alloprevotella,and Prevotellaceae_UCG-001,and a significant increase in Lachnospiraceae_NK4A136_group,Bacteroides,and Helicobacter.After admin-istering Budi Shenlian Recipe to CRC mice,the community structure of some mice partially reverted to the level of the blank group.Transcriptome sequencing revealed that the most significant biological process(BP)among upregulated genes was the negative regulation of macrophage migration,suggesting that Budi Shenlian Recipe can reduce macrophage migration.Moreover,compared to the model group,the proportion of TAMs cells in the tumor tissues of the Budi Shenlian Recipe group significantly decreased(P<0.001).Simultaneously,compared to the model group,the proportion of M1 type TAMs in the Budi Shenlian Recipe group significant-ly increased(P<0.000 1),while the proportion of M2 type TAMs significantly decreased(P<0.05).Immunofluorescence analysis showed the same trend as flow cytometry.The content of TNF-α in tumor tissues of the Budi Shenlian Recipe group significantly in-creased(P<0.001),and IL-10 content significantly decreased(P<0.001).Additionally,compared to the MFMT group,the tumor volume in the BFMT group grew more slowly(P<0.0001).HE staining showed increased necrotic areas,sparser cell arrangement,and reduced pathological mitosis in the BFMT group.Furthermore,compared to the MFMT group,the proportion of TAMs cells in the tumor tissues of the BFMT group significantly decreased(P<0.01).Compared to the MFMT group,the proportion of M1 type TAMs cells in the BFMT group increased(P<0.000 1),while the proportion of M2 type TAMs cells decreased(P<0.01).Immunofluores-cence analysis further confirmed that Budi Shenlian Recipe fecal microbiota transplantation can reduce the proportion of TAMs in the tumor tissues of CRC mice and promote the conversion from M2 to M1 type,thereby reducing immune suppression in the tumor micro-environment.CONCLUSION Budi Shenlian Recipe can improve gut microbiota dysbiosis in CRC mice and exert anti-CRC effects by reducing tumor infiltration of TAMs and modulating the phenotypic transition of TAMs.There may be a certain correlation between these two effects.

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Squamous Cell/virology* ; Human Papillomavirus Viruses/isolation & purification* ; Margins of Excision ; Oropharyngeal Neoplasms/virology* ; Papillomavirus Infections/virology* ; Prognosis ; Prospective Studies ; Robotic Surgical Procedures/methods*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: To develop a digital intelligent multimodal shift handover system for the intensive care unit (ICU) and evaluate its application effect in ICU shift handovers. METHODS: A research and development team was established, consisting of 1 department director, 1 head nurse, 3 information technology engineers, 3 nurses, and 2 doctors. Team members were assigned responsibilities including overall coordination and planning, platform design and maintenance, pre-application training, collection and organization of clinical feedback, and research investigation respectively. A digital intelligent multimodal shift handover system was developed for ICU based on the Shannon-Weaver linear transmission model. This innovative system integrated automated data collection, intelligent dynamic monitoring, multidimensional condition analysis and visual reporting functions. A cloud platform was used to gather data from multi-parameter vital signs monitors, infusion pumps, ventilators and other devices. Artificial intelligence algorithms were employed to standardize and analyze the data, providing personalized recommendations for healthcare professionals. A self-controlled before-after method was adopted. Before the application of the ICU digital intelligent multimodal shift handover system (from December 2023 to March 2024), the traditional verbal bedside handover was used; from June 2024 to March 2025, the ICU digital intelligent multimodal shift handover system was applied for shift handovers. Questionnaires before the application of the shift handover system were collected in April 2024, and those after the application were collected in April 2025. The shift handover time, handover quality (scored by the nursing handover evaluation scale), satisfaction with doctor-nurse communication (scored by the ICU doctor-nurse scale) before and after the application of the handover system were compared, and nurses' satisfaction with the shift handover system (scored by the clinical nursing information system effectiveness evaluation scale) was investigated. RESULTS: After the application of the ICU digital intelligent multimodal shift handover system, the shift handover time was significantly shorter than that before the application [minutes: 20 (15, 25) vs. 30 (22, 40)], the handover quality was significantly higher than that before the application [score: 84.0 (78.0, 88.5) vs. 71.0 (55.0, 79.0)], and the satisfaction with doctor-nurse communication was also significantly higher than that before the application (score: 84.58±6.79 vs. 74.50±11.30). All differences were statistically significant (all P < 0.05). In addition, the nurses' system effectiveness evaluation scale score was 102.30±10.56, which indicated that nurses had a very high level of satisfaction with the ICU digital intelligent multimodal shift handover system. CONCLUSIONS The application of the ICU digital intelligent multimodal shift handover system can shorten the shift handover time, improve the handover quality, and enhance the satisfaction with doctor-nurse communication. Nurses have a high level of satisfaction with this system.
Intensive Care Units ; Humans ; Patient Handoff ; Artificial Intelligence ; Algorithms

Objective This study comprehensively analyzes the current implementation status and influencing factors of the"Administrative Measures for Surplus Drugs of Medical Institutions(Trial)"(referred to as the"Measures"),it helps solve the problems that have long plagued the management of surplus drugs in medical institutions.Methods Based on the framework of Health Policies Triangle,starting from the policy content,and from the perspectives of various actors,a questionnaire was designed from three dimensions:the current implementation status,the implementation effect,and the countermeasures suggestions.The management of surplus drugs in secondary and tertiary medical institutions throughout the province was investigated,then we will analyze the investigation results,evaluate the implementation effectiveness and influencing factors,and propose targeted suggestions.Results 84%of medical institutions have fully or partially implemented the measure,The implementation of the"Measures"has prevented hospitals from being subject to administrative penalties again due to surplus drugs,determined the disposal methods for surplus drugs,promoted the establishment of surplus drug management systems and directories by implementing hospitals,and clarified the varieties of surplus drugs in Shanxi Province.Conclusion The"Method"has significant implementation effects and clarified management provisions and filled the gaps in current management.The problems encountered include:The definition of surplus medicines limits the implementation of the"Measures"in secondary hospitals;The measures to reduce surplus drugs at the source have not been detailed;the awareness of the content of the"Measures"is insufficient;the collaboration among departments is lacking.It is suggested to revise and implement the"Measures"by clarifying the categories of drugs that can be charged by the unit and management rules in Shanxi Province,optimizing the definition of surplus drugs,clarifying the management regulations of each department,refining the informed consent method of patients,expanding the scope of special funds.In addition,the publicity efforts for"Measures"need to be strengthen,in order to further solve the problem of surplus drug management in medical institutions.

BACKGROUND:Copper is an essential trace element and plays a key role in series of physiological activities in the body.Metabolic disturbance of copper is closely associated with multiple diseases.Copper metabolism is mainly involved in the absorption,transport,storage and excretion of copper ions,and all the above processes regulate copper homeostasis in the body.In recent years,many studies have confirmed that copper homeostasis disorder severely affects the metabolic activities of the body and cause diseases in various systems.Besides,the role of copper in oral diseases has been of great interest.OBJECTIVE:To explore the role of copper in occurrence,development,and treatment of oral diseases,and provide a comprehensive overview of research advances in this field.METHODS:The first author searched relevant studies on copper in oral diseases using a computer in PubMed,Web of Science,and CNKI.The key words were"Cu,copper,copper metabolism,oral diseases,oral squamous cell carcinoma,periodontitis,oral submucous fibrosis,oral lichen planus,recurrent oral ulceration,pultitis"in English and Chinese.After screening,78 articles were included for further review and analysis.RESULTS AND CONCLUSION:(1)Patients with oral squamous cell carcinoma have elevated concentrations of copper in serum and saliva,and elevated copper promotes cancer progression through oxidative stress and promoting angiogenesis.Excessive elevation or reduction of copper concentration in tumor cells can inhibit the growth of tumor cells.The combination of copper and anticancer drugs can significantly improve the efficacy of drugs.(2)The concentration of copper in the serum of patients with periodontitis is increased,and excessive copper can aggravate periodontitis through promoting oxidative stress.Combination of copper and drugs can promote periodontal bone regeneration and periodontal tissue healing.(3)The level of copper is positively correlated with degree of oral mucosa fibrosis.Copper that enters the oral mucosa promotes fibrosis of oral mucosa by enhancing activity of lysyloxidase to increase production of collagen.(4)Copper levels are elevated in patients with oral lichen planus,and elevated copper may promote the progression of oral lichen planus by modulating immune cell function.(5)In patients with recurrent oral ulcers,serum copper level is significantly increased,and utilization of copper becomes disordered,which could decrease copper-containing enzyme activity,thus affecting the healing of ulcers.Copper is closely associated with multiple oral diseases and therapies targeting at copper could obviously enhance the therapeutic effect of drugs.But further studies are still needed to uncover its mechanisms to lay foundation for the better treatment of oral diseases.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.