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。

ObjectiveTo investigate the impact of preoperative frailty on the prognosis of patients with pancreatic cancer who underwent pancreaticoduodenectomy. MethodsA retrospective analysis was conducted on the clinical data of 435 pancreatic cancer patients who underwent pancreaticoduodenectomy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Preoperative frailty was assessed using the FRAIL questionnaire. Binary logistics regression analysis was employed to identify factors influencing frailty， and Cox regression analysis was used to evaluate the effect of frailty on survival. According to the demographic characteristics， subgroup analyses were performed on the effect of frailty on prognosis of patients with pancreatic cancer with pancreaticoduodenectomy. ResultsAmong the 435 patients enrolled， 119 （27.4%） exhibited frailty， while 316 （72.6%） did not. Significant differences were observed between the two groups in various clinical parameters， including age， body mass index， American Society of Anesthesiologists （ASA） score， postoperative red blood cell transfusion， postoperative abdominal abscess， serum levels of glycoantigens 199， glycoantigens 125， and alpha fetoprotein， leukocyte count， neutrophil， high density lipoprotein （HDL） level， and pain intensity （P＜0.05）. Advanced age and an ASA score of Ⅲ were identified as risk factors for frailty， whereas HDL level was a protective factor. Non-frail patients had better postoperative survival times than frail patients. HDL was determined to be an independent protective factor for prognosis， while LDL was an independent risk factor. ConclusionsThis study demonstrates that preoperative frailty is a significant predictor of poor prognosis in pancreatic cancer patients who underwent pancreaticoduodenectomy.These findings suggest that preoperative frailty assessment and targeted interventions to improve nutritional and metabolic status could potentially enhance postoperative survival and quality of life in pancreatic cancer patients.

Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice. Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue. Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05). Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVE To systematically evaluate the influential factors for the clinical efficacy of tigecycline in the treatment of severe infections caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）. METHODS Retrieved from PubMed， Embase， The Cochrane Library， CNKI database， Wanfang database and VIP database， the studies about the influential factors for the clinical efficacy of tigecycline in the treatment of adult patients with severe infections caused by MDR-GNB from the database construction to April 30， 2025. After screening literature， extracting data and evaluating the quality of literature， systematic review was performed by using RevMan 5.3 software. RESULTS A total of 14 studies involving 2 033 patients were included， of which 1 355 patients showed effective treatment outcomes. The meta-analysis results showed that Acute Physiology and Chronic Health Evaluation （APACHE）-Ⅱ ＞ 20 [OR＝4.50， 95%CI （2.28， 8.85）， P＜0.001]， malignant tumor [OR＝1.96， 95%CI （1.41， 2.72）， P＜0.001]， hemodialysis [OR＝2.09， 95%CI （1.40， 3.12）， P＜0.001]， septic shock [OR＝3.07， 95%CI （2.00， 4.72）， P＜0.001]， mechanical ventilation [OR＝2.31， 95%CI （1.57， 3.39）， P＜0.001]， coagulation dysfunction [OR＝ 3.03， 95%CI （2.09， 4.37）， P＜0.001]， glucocorticoids use＞3 days [OR＝2.26， 95%CI （1.14， 4.45）， P＝0.020]， and longer hospitalization time before using tigecycline [OR＝3.33， 95%CI （1.34， 8.30）， P＝0.010] were risk factors for the clinical efficacy of tigecycline in treatment of severe infections caused by MDR-GNB. Tigecycline initial double-dose regimen [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.001]， combination therapy [OR＝0.15， 95%CI （0.05， 0.48）， P＝0.001]， and prolonged treatment course [OR＝0.91， 95%CI （0.88， 0.95）， P＜0.001] were protective factors. CONCLUSIONS There are many influential factors for the clinical efficacy of tigecycline in the treatment of severe infections caused by MDR-GNB， among which APACHE-Ⅱ score＞20， malignant tumor， hemodialysis， septic shock， mechanical ventilation， coagulation dysfunction， glucocorticoids＞3 d and longer hospitalization time before using tigecycline before tigecycline （No.20251606） use are risk factors； tigecycline double dose， combined medication and longer treatment course are protective factors.