Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Implementation Science is an interdisciplinary field dedicated to systematically studying how to effectively translate evidence-based research findings into practical application and implementation. In the health-related context, it focuses on enhancing the efficiency and quality of healthcare services, thereby facilitating the transition from scientific evidence to real-world practice. This article elaborates on Theories, Models, and Frameworks (TMF) within health-related Implementation Science, clarifying their basic concepts and classifications, and discussing their roles in guiding implementation processes. Furthermore, it reviews and prospects current research from three aspects: the constituent elements of TMF, their practical applications, and future directions. Five representative frameworks are emphasized, including the Consolidated Framework for Implementation Research (CFIR), the Practical Robust Implementation and Sustainability Model (PRISM), the Exploration, Preparation, Implementation, Sustainment (EPIS)framework, the Behavior Change Wheel (BCW), and the Normalization Process Theory (NPT). Additionally, resources such as the Dissemination & Implementation Models Webtool and the T-CaST tool are introduced to assist researchers in selecting appropriate TMFs based on project-specific needs.

Background and purpose:Exogenous bone morphogenetic protein 9(BMP9)inhibits the malignant progression of human breast cancer,but its expression is often abnormally low in breast cancer.In this study,we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A(KDM4A)in breast cancer,and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism.Methods:The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Chromatin immunoprecipitation(ChIP)verified the regulatory role of KDM4A on BMP9,and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression.Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA(siKDM4A)or infected with siBMP9 adenovirus(Ad-siBMP9)were constructed using RNA interference technology and adenoviruses knocking down BMP9,and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay,respectively.Results:Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues,and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer;RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines,and the knockdown of KDM4A significantly up-regulated BMP9.ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene,reducing its histone lysine 36 position instead of position 4 methyl status,thus silencing the expression of BMP9.RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9,but could affect its protein degradation.After knocking down KDM4A,the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited,and this effect could be partially reversed by knocking down BMP9.Conclusion:KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231,and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene,as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA,and promoting the migration and invasion of breast cancer.

Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.

Regional party building has been an important exploration in innovating grassroots party building in recent years.Under the comprehensive implementation of the requirements for party building in the new era,public hospitals have a-chieved the sharing and extension of medical resources through system and mechanism reforms and innovations.Based on the re-gional party building,it has become an inevitable requirement to explore the new era of party building in public hospitals.This study analyzes the current challenges faced by hospitals participating in regional party building work and combines the practical experience of regional party building work in Shuguang Hospital,affiliated to Shanghai University of Traditional Chinese Medi-cine.It promotes paths such as party building leading joint construction,expanding the scope of medical volunteer services,and promoting the deep integration of party building and business work.This will further improve the quality of people's lives,ulti-mately achieving"mutual benefit"through"resource sharing."