ObjectiveTo develop a core outcome set for musculoskeletal pain （MKP-COS） and a specific outcome set for traditional Chinese medicine external treatment （MKP-SOS-ETCM）， providing a standardized basis for clinical research in musculoskeletal pain and serving as a reference for core outcome set （COS） development in related fields. MethodsExisting COS studies on musculoskeletal pain （MKP） were systematically searched， and core outcome indicators were extracted to form an initial item pool. The Delphi method was used， in which experts were invited to reach consensus on MKP-COS and MKP-SOS-ETCM. The inclusion criteria for consensus are set as an importance score of 7-9 points with ≥75% of experts reaching agreement. ResultsA total of 47 COS studies were included， and after discussion and consolidation， a preliminary item pool containing 34 outcome indicators was established. After three rounds of Delphi expert consensus， MKP-COS was identified， including five outcomes including pain， motor function， joint range of motion， activities of daily living， and adverse events/ adverse reactions； MKP-SOS-ETCM included six outcomes involving stiffness （including morning stiffness）， joint tenderness count， work status/ productivity， overall physician assessment， structural damage， and muscle strength. ConclusionThis study has established MKP-COS and MKP-SOS-ETCM， forming a dual-dimensional outcome assessment system integrating both disease commonality and intervention specificity.

Objective To investigate the status quo of limited social participation in young patients with ankylosing spondylitis (AS), and analyze its influencing factors. Methods Using the random number table method, a simple random sampling method was employed to select 320 young patients with ankylosing spondylitis who were admitted to the First Affiliated Hospital of Naval Medical University from June 2023 to June 2025. Chinese version of social participation scale was applied to evaluate the level of social participation of patients. The above patients were classified into unlimited group (n=148) and limited group (n=172). Logistic regression analysis was performed to analyze the independent influencing factors for limited social participation. Results Compared with the unlimited group, the limited group exhibited longer course of AS, higher BASDAI score, BASFI score, HAMA score, HAMD score and ASQoL score as well as lower PSSS score (P<0.05). Logistic regression analysis suggested that course of disease, high disease activity score, high anxiety score, high depression scores and low social support scores are the relevant factors for the restricted social participation of young patients with ankylosing spondylitis. Conclusion The phenomenon of limited social participation is common in young patients with AS, and its occurrence is the result of a combination of factors such as disease course, disease activity, anxiety, depression and social support level.

ObjectiveTo develop a core outcome set for musculoskeletal pain （MKP-COS） and a specific outcome set for traditional Chinese medicine external treatment （MKP-SOS-ETCM）， providing a standardized basis for clinical research in musculoskeletal pain and serving as a reference for core outcome set （COS） development in related fields. MethodsExisting COS studies on musculoskeletal pain （MKP） were systematically searched， and core outcome indicators were extracted to form an initial item pool. The Delphi method was used， in which experts were invited to reach consensus on MKP-COS and MKP-SOS-ETCM. The inclusion criteria for consensus are set as an importance score of 7-9 points with ≥75% of experts reaching agreement. ResultsA total of 47 COS studies were included， and after discussion and consolidation， a preliminary item pool containing 34 outcome indicators was established. After three rounds of Delphi expert consensus， MKP-COS was identified， including five outcomes including pain， motor function， joint range of motion， activities of daily living， and adverse events/ adverse reactions； MKP-SOS-ETCM included six outcomes involving stiffness （including morning stiffness）， joint tenderness count， work status/ productivity， overall physician assessment， structural damage， and muscle strength. ConclusionThis study has established MKP-COS and MKP-SOS-ETCM， forming a dual-dimensional outcome assessment system integrating both disease commonality and intervention specificity.

Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in neck, shoulders and lower back among power grid workers. Methods A total of 371 workers from a power grid enterprise in Guangdong Province were selected as the research subjects using the convenience sampling method. A cross-sectional survey of WMSDs in the neck, shoulders and waist of the workers was conducted using the modified Musculoskeletal Disorders Questionnaire. Results The overall prevalence of WMSDs among the power grid workers was 62.8%, with prevalence of 37.2%, 33.7% and 32.1% for WMSDs in neck, shoulders and lower back, respectively. Binary logistic regression analysis showed that power grid workers who did not maintain a good sitting posture or were unable to maintain good sitting posture over prolonged periods had a higher risk of neck WMSDs than those who maintained a good sitting posture (both P<0.01). A higher frequency of head-down posture during work was associated with an increased risk of neck WMSDs (both P<0.05). Female workers had a higher risk of shoulder WMSDs than male workers (P<0.05). A higher frequency of early awakening with inability to fall back asleep, as well as a higher frequency of head-down posture during work, were both associated with an increased risk of shoulder WMSDs (all P<0.05). Workers with a sedentary habit had a higher risk of shoulder WMSDs than those without (P<0.01). Workers with insufficient rest time had a higher risk of shoulder WMSDs than those with sufficient rest time (P<0.01). Both maintenance workers and managers had a higher risk of lower back WMSDs than workers in other occupational categories (all P<0.05). Workers who experienced nocturnal awakening with difficulty falling back asleep at frequency of several times per year, ≥1 time /month, ≥1 time /week, had higher risk of lower back WMSDs than those who never experienced such problem (all P<0.05). Workers with a sedentary habit and those uncertain about having a sedentary habit both had a higher risk of lower back WMSDs than those without (both P<0.05). Greater forward neck flexion during work was associated with an increased risk of lower back WMSDs (both P<0.05). Workers who occasionally tilted their necks to the side while working had a higher risk of lower back WMSDs than those who did not (P<0.05). Conclusion WMSDs are highly prevalent among power grid workers, particularly affecting the neck, shoulder, and waist. Influencing factors include individual characteristics, behavioral habits, work organization, work posture, and workload. Maintaining proper posture and adequate rest may reduce the risk of WMSDs.

[摘 要] 目的：探讨年轻乳腺癌独特的DNA甲基化特征，筛选与预后相关的甲基化位点，构建并验证预后预测模型，并通过多组学整合及关键蛋白验证评估其临床价值。方法：收集癌症基因组图谱（TCGA）数据库中的乳腺癌样本DNA甲基化及临床数据，筛选年轻乳腺癌特有的甲基化位点。采用随机森林、LASSO回归及单因素和多因素Cox比例风险回归分析构建预后模型。使用受试者工作特征（ROC）曲线、校准曲线和一致性指数（C-index）评估模型性能，并比较高、低风险组间的多组学特征差异，在独立队列中通过免疫组化法检测模型关键基因LAMA5的蛋白表达，分析其与预后的关系。结果：年轻乳腺癌相较于老年乳腺癌，在启动子区域（尤其是CpG岛）呈现显著低甲基化特征。通过多步骤差异分析获得3 489个年轻乳腺癌特有的甲基化位点，经Cox比例风险回归筛选出12个与总生存期（OS）独立相关的位点，其中启动子区、基因体区和基因间区位点各4个。基于筛选出的12个甲基化位点构建的预测模型，在TCGA训练集中显示出良好的区分度，高风险组总生存期显著更差（P = 0.002 5），5、8和10年OS预测曲线下面积（AUC）达0.88～0.94。多组学分析显示，高风险组丝裂原活化蛋白激酶（MAPK）信号通路激活，TP53基因突变频率更高，雌激素受体α蛋白表达较低。将TP53突变状态及雌激素受体1（ESR1）mRNA表达水平等关键多组学指标纳入模型，构建综合列线图，其预测效能进一步提升。组织芯片验证显示，模型关键基因LAMA5蛋白表达阴性患者的OS更差（P = 0.046），且富集于三阴性乳腺癌，与模型高风险组的临床病理特征一致。结论：整合启动子和非启动子区域信息的基于12个甲基化位点的模型可用于年轻乳腺癌患者的预后分层。联合年龄、TP53突变及ESR1 mRNA表达水平构建的综合列线图显示出较单一甲基化模型更高的预测效能。

Deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (CRC) is highly sensitive to immune checkpoint inhibitors due to the high tumor mutation load and neoantigen enrichment. However, 45%-60% of patients exhibit primary or acquired immunotherapy resistance. The mechanisms underlying this resistance are complex, involving tumor microenvironment heterogeneity, co-expression of multiple immune checkpoints, aberrant activation of oncogenic pathways, metabolic dysregulation, intestinal microbiota imbalance, HLA-Ⅰ molecule defects, and epigenetic regulation. Current strategies aimed at reversing immunotherapy resistance include combination immunotherapies, personalized neoantigen vaccines, intestinal microbiota transplantation, epigenetic interventions, and adoptive immune cell therapies. Further analysis of the potential mechanisms of immune therapy resistance in dMMR/MSI-H metastatic CRC, and the exploration of current strategies to overcome resistance can provide a theoretical basis for reversing the immunotherapy resistance in such patients.

Objective:Effects of Qingsui Xiaoyan Decoction on osteoclast differentiation of RAW264.7 cells.Methods:Receptor activator of nuclear factor kappa B ligand (RANKL) was used to induce differentiation of RAW264.7 cells into osteoclasts. CCK-8 method was used to screen experimental drug concentrations and analyze the cytotoxicity of drug intervention on RAW264.7 cells. TRAP staining method was used to quantitatively detect the effects of Qingsui Xiaoyan Decoction on osteoclast differentiation ability. RT-PCR technology was used to detect the mRNA expressions of osteoclast differentiation genes TRAP, MMP-9, CK, CTR. Western blot was used to detect osteoclast-related protein expressions of NF-κBP65, IκB-αTRAP, and TRAP.Results:After 72 hours of intervention, 0.800, 4.000, 20.000, and 100.000 mg/ml of Qingsui Xiaoyan Decoction could inhibit cell proliferation ( P<0.05). Compared with the model group, the number of TRAP-positive cells decreased ( P<0.05) in the 5, 20, 80, and 160 μg/ml Qingsui Xiaoyan Decoction groups. Additionally, the mRNA levels of TRAP, MMP-9, CK, and CTR decreased ( P<0.05), the expression of NF-κB p65 and TRAP proteins decreased ( P<0.05), and the expression of IκB-α protein increased ( P<0.05). Conclusions:Qingsui Xiaoyan Decoction can inhibit the expressions of TRAP, MMP-9, CK, CTR genes and TRAP protein, reduce the degradation of I κ B - α protein by inhibiting the NF - κ B signaling pathway, inhibit the expression of NF - κ B p65 protein, and thus inhibit the differentiation of RAW264.7 into osteoclasts.

In recent years, the relationship between intestinal flora dysbiosis and abnormal bile acid metabolism and anxiety has received widespread attention. This article discussed the biological mechanism of the pathogenesis of anxiety from the perspective of intestinal flora and bile acid metabolism, in order to provide new ideas and theoretical basis for the TCM prevention and treatment of anxiety. According to TCM, spleen and stomach belong to earth, liver and gallbladder belong to wood, when spleen qi is healthy, the normal distribution of water and grain essence can be achieved, so that the liver can be nourished, qi and blood is sufficient, and its excretory function is normal, and the bile is sufficient. Once the spleen is not healthy, the distribution of water and grain essence is good, affecting the metabolism of fluids, resulting in phlegm and dampness, the qi is not smooth, can affect the liver's excretory function; liver and wood depression for a long time, transgressing the spleen and earth, qi and blood lack of biochemical sources, the formation of soil congestion and wood depression of the pathological phenomenon will appear. From the viewpoint of modern medicine and molecular biology, changes in the structure of intestinal flora affect the organism through neurological, endocrine, immune and metabolic pathways, which is consistent with the pathogenesis of "congestion of the earth"; disorders in the metabolism of bile acids can lead to changes in neurotransmitters and synaptic structure in the brain, causing anxiety symptoms, which is consistent with the characteristics of "wood depression". The bile acid metabolism disorder can cause neurotransmitter and synaptic structure changes in the brain, causing anxiety symptoms, which is consistent with the characteristics of "wood depression". It is important to regulate the intestinal flora and bile acid metabolism pathway to ease the liver and strengthen the spleen to improve anxiety.

Objective To investigate the differences in pathological changes and immune responses of human airway organoids at different stages of differentiation following respiratory syncytial virus(RSV)infection.Methods Models of human fetal lung organoids(FLO)and induced airway organoids(iAO)were established to simulate immature and mature airway epithelium.Immunofluorescence staining,electron microscopy,and quantitative polymerase chain reaction(Q-PCR)were used to confirm the successful construction of the lung organoid models.Human lung organoids were infected with RSV,and samples were collected at 6 and 48 hours post-infection.The immune characteristics of immature and mature RSV-infected organoids were assessed using immunofluorescence staining,droplet digital PCR(DDPCR),and Q-PCR.Results We successfully generated FLO expressing both the progenitor markers sex determining region Y-box transcription factor 2(SOX2)and sex determining region Y-box transcription factor 9(SOX9),as well as iAO containing basal cells,ciliated cells,club cells,and goblet cells.In addition,organoid models of RSV infection were established.DDPCR results showed that,at the initial stage of RSV infection,the viral load in iAO was significantly higher than that in FLO(P＜0.001).However,at 48 hours post-infection,the viral load in iAO was lower than that in FLO(P＜0.05).Q-PCR results indicated that the expression of RSV infection receptor genes,including epidermal growth factor receptor(EGFR),insulin-like growth factor 1 receptor(IGF1R),and nucleolin(NCL),was significantly higher in iAO compared to that in FLO(P＜0.001).RSV infection led to an increase in the expression levels of immune factors,including interleukin 6(ILL-6),interleukin 8(CXCL8),interferon α(IFN-α),granulocyte colony-stimulating factor(G-CSF),granulocyte-macrophage colony-stimulating factor(GM-CSF),and tumor necrosis factor α (TNF-α),in iAO compared to those in FLO,and the differences were statistically significant(P＜0.05).Conclusion The expression of RSV infection receptor proteins increases with airway maturation,and mature airway epithelial cells exhibit a stronger immune response than immature ones do,effectively inhibiting RSV replication.

Objective To explore the application value of distortion product otoacoustic emission (DPOAE) and speech in noise(SIN) testing in occupational health surveillance of noise-exposed workers. Methods A total of 220 noise-exposed workers was selected as the study subjects using the convenient sampling method. The study subjects participated questionnaire survey, personal noise exposure assessment, acoustic immittance testing, pure tone audiometry (PTA), DPOAE and SIN testing. According to PTA results, workers were enrolled into a high-frequency hearing loss (HFHL) group and a non-HFHL group. Results The detection rate of HFHL among the study subjects was 41.4%, and the detection rate of speech-frequency hearing loss was 15.9%. Workers′ bilateral DPOAE response amplitudes and signal-to-noise ratios at frequencies of 2.0-8.0 kHz in the HFHL group were lower than those in the non-HFHL group (all P<0.05). The DPOAE amplitudes at frequencies of 1.0-8.0 kHz in both ears of the study subjects were negatively correlated with the PTA threshold (all P<0.01), and were negatively correlated with age (all P<0.01). The signal-to-noise ratio loss score was higher among worker in the HFHL group than in the non-HFHL group (P<0.01) and was positively correlated with PTA thresholds (P<0.05). Conclusion DPOAE and SIN testing can detect early cochlear outer hair cell impairment and reduction of noise-related speech recognition ability in noise-exposed workers and may serve as an effective supplementary tool to routine PTA in occupational hearing surveillance.