ObjectiveTo establish a reliable chronic obstructive pulmonary disease (COPD) mouse model based on a self-developed multichannel automatic control system for long-term continuous cigarette smoke exposure in small animals using a novel continuous cigarette smoke exposure method, and to conduct phenotypic evaluation and analysis, thereby providing an animal experimental basis for investigating COPD pathogenesis and prevention strategies. MethodsTwenty male C57BL/6J mice aged 6 weeks were randomly and equally divided into a control group and a model group. The model group (n=10) underwent 6 h of continuous cigarette smoke exposure daily (6 cigarettes per day for 12 consecutive weeks), while the control group (n=10) received no intervention. Body weight was monitored biweekly. Post-exposure, in vivo micro-CT imaging was performed. After euthanasia, serum and bronchoalveolar lavage fluid (BALF) levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified by ELISA. Lung tissues underwent H&E and Masson's trichrome staining to observe changes in lung morphology and inflammatory cell infiltration, and the mean linear intercept (MLI) was calculated, thereby comprehensively evaluating the clinical features of COPD in the mouse model. ResultsCompared with the control group, the model group showed significantly reduced body weight (P<0.01) from the fourth week. Compared with the control group, IL-6 level in the serum and BALF of the model group increased by 27.2% and 140.0%, respectively (P<0.01). TNF-α level in the serum and bronchoalveolar lavage fluid of the model group increased by 16.7% (P<0.01) and 19.3% (P<0.05), respectively. Histopathological examination revealed alveolar wall thinning, septal rupture, emphysematous bullae formation, reduced alveolar count, bronchial wall thickening with lumen narrowing, and inflammatory cell infiltration. MLI was significantly elevated (P<0.01). Masson's staining confirmed collagen deposition and bronchial remodeling. Micro-CT demonstrated localized high-density shadows exhibiting typical features of chronic bronchitis. Conclusion The self-developed device enables long-term continuous smoke exposure, and the successfully established COPD mouse model exhibits pathological features highly consistent with clinical manifestations, offering an efficient and reliable tool for COPD research.

Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

To promote the high-quality development of healthcare in the highland areas and to enable traditional Chinese medicine(TCM)to make a more prominent contribution to the healthcare of the people in these areas,it is imperative to clarify the roles of TCM in the formation of the healthcare system in the past and present,as well as the direction of innovative development of TCM in the plateau in the future.To this end,this paper first systematically reviews the literature to summarize the influence of TCM on the cultural background,theoretical framework,and practical system of Tibetan medicine during its origin,development,and maturation;then,through the example of typical cases,it elaborates on the direct practical applications of TCM in the prevention and treatment of a series of highland diseases from the perspectives of pathogenesis,therapeutic principles,unique drugs,and techniques;finally,it deeply reflects on a series of problems restricting the integration,inheritance,and innovative development of TCM in the highland areas and puts forward targeted suggestions to enable TCM to serve and safeguard the health of people living in the plateaus better together with the local ethnic medicine.

Osteoarticular diseases,common chronic degenerative disorders in the elderly,involve the gradual deterioration and degeneration of bones or joints.The metabolic capacity declines with age.Impaired bone metabolism dis-rupts homeostasis,leading to osteoarticular dysfunctions.Cuprotosis,a novel form of programmed cell death mediated by ferredoxin 1,matters for the pathologic process in osteoarticular diseases.Cuprotosis influences the levels of intercellular signal transduction to induce oxidative stress,inflammation,pyroptosis,and ferroptosis in joints.Those cell death and mi-tochondrial dysfunction ultimately exacerbate the progression of osteoarticular diseases.Therefore,this review summarizes the mechanism of copper homeostasis-cuprotosis in osteoarticular diseases and the potential applications targeting copper homeostasis-cuprotosis.

Objective:To investigate the relationship between dietary behavior and sarcopenia in older adults aged ≥65 years in longevity areas of China based on latent class analysis.Methods:A total of 4 358 older adults aged ≥65 years were selected from the 2021 Healthy Aging and Biomarkers Cohort Study. The information about their demographic characteristics, lifestyles, and chronic disease histories were collected. A simplified food frequency questionnaire was used to collect information about their dietary intake in the last month. The food intake frequency and food category score were calculated, and the higher the food category score, the richer the dietary intake. Latent class analysis was used to identify the latent classes of the dietary behavior. Sarcopenia was diagnosed using the SARC-CalF. Multivariate logistic regression model was used to analyze the association of food category scores and different latent classes of the dietary behavior with the risk for sarcopenia.Results:In 4 358 older adults, 1 841 (42.24%) had sarcopenia. The frequencies of intakes of cereals and potatoes, vegetable and fruit, meat and bean products were lower in the sarcopenia group than in the non-sarcopenia group. The risk for sarcopenia decreased with the increase of food category score in older adults ( OR=0.850, 95% CI: 0.796-0.907). Latent class analysis identified 4 latent classes of the dietary behavior. Compared with those with class 1 (frequency of intake of all 5 food species was higher probability in T3 group), those with class 2 (frequency of intake of vegetables and fruits and energy-only foods were less likely to be in the T3 group) and class 3 (frequency of intake of all 5 food species was lower probability in T3 group) had significantly increased risk for sarcopenia ( OR=1.377, 95% CI: 1.131-1.676) and ( OR=1.354, 95% CI: 1.091-1.680), 37.7% and 35.4% increased risk for sarcopenia, respectively. Conclusion:Increasing dietary intake category and sufficient intake of various foods for a balanced dietary pattern can reduce the risk of sarcopenia in older adults.

Objective:To investigate the relationship between dietary behavior and sarcopenia in older adults aged ≥65 years in longevity areas of China based on latent class analysis.Methods:A total of 4 358 older adults aged ≥65 years were selected from the 2021 Healthy Aging and Biomarkers Cohort Study. The information about their demographic characteristics, lifestyles, and chronic disease histories were collected. A simplified food frequency questionnaire was used to collect information about their dietary intake in the last month. The food intake frequency and food category score were calculated, and the higher the food category score, the richer the dietary intake. Latent class analysis was used to identify the latent classes of the dietary behavior. Sarcopenia was diagnosed using the SARC-CalF. Multivariate logistic regression model was used to analyze the association of food category scores and different latent classes of the dietary behavior with the risk for sarcopenia.Results:In 4 358 older adults, 1 841 (42.24%) had sarcopenia. The frequencies of intakes of cereals and potatoes, vegetable and fruit, meat and bean products were lower in the sarcopenia group than in the non-sarcopenia group. The risk for sarcopenia decreased with the increase of food category score in older adults ( OR=0.850, 95% CI: 0.796-0.907). Latent class analysis identified 4 latent classes of the dietary behavior. Compared with those with class 1 (frequency of intake of all 5 food species was higher probability in T3 group), those with class 2 (frequency of intake of vegetables and fruits and energy-only foods were less likely to be in the T3 group) and class 3 (frequency of intake of all 5 food species was lower probability in T3 group) had significantly increased risk for sarcopenia ( OR=1.377, 95% CI: 1.131-1.676) and ( OR=1.354, 95% CI: 1.091-1.680), 37.7% and 35.4% increased risk for sarcopenia, respectively. Conclusion:Increasing dietary intake category and sufficient intake of various foods for a balanced dietary pattern can reduce the risk of sarcopenia in older adults.

Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.