Objective To analyse and explore whether there is a causal association without confounding factors between malignant haematological diseases and frailty based on a bidirectional Mendelian randomisation(MR)analysis,and to provide a theoretical basis for clinical management of the frailty associated with malignant haematological diseases.Methods In December 2023,the IEU OpenGWAS database(https://gwas.mrcieu.ac.uk/)was searched to acquire the datasets in genome-wide association studies(GWAS)derived from non-overlapping multi-ethnic populations based on Mendelian Randomisation(MR)analysis.The bidirectional causal association was verified utilising the two-sample MR approach.Single nucleotide polymorphisms(SNPs)of the frailty index(FI)(n=175,226),haematological malignancies(n=212,453),multiple myeloma/malignant plasmacytoma(n=218,792),and follicular lymphoma(n=181,278)were used as the study instruments.Results The analysis with the statistic inverse variance weighted method(IVW)showed that haematological malignancies(OR=1.00,95%CI:0.98-1.00,P=0.797),multiple myeloma/malignant plasma cell tumours(OR=1.00,95%CI 0.99～1.01,P=0.982),and follicular lymphoma(OR=1.00,95%CI:0.99～1.01,P=0.314)were not causally associated with genetically predicted FI.Similarly,FI was not significantly or causally correlated with haematological malignancies(OR=0.89,95%CI:0.25～3.12,P=0.861),multiple myeloma/malignant plasma cell tumours(OR=0.52,95%CI:0.00～3.13,P=0.473),and follicular lymphoma(OR=1.06,95%CI:0.00～5.19,P=0.944).Conclusion No causal relationship between the malignant haematological diseases and frailty was found in this study.It suggests that other factors might exist to cause the malignant haematological frailty.

Traditional Chinese medicine upholds the unity of nature and humanity as its fundamental principle,asserting that man is in harmony with heaven and earth and corresponds to the sun and moon.Human life processes align with the circadian rhythms of nature,exhibiting periodic temporal changes-concepts that Western medicine defines as biological rhythms.The"opening-closing-pivot"of the three yin and three yang meridians represents the primary mode of interaction between nature and humanity.This mechanism regulates the transformation of yin and yang to qi within the body,ensuring synchronization with the circadian rhythm.Building upon this foundation,the concept of"the harmony of rhythms and states"was proposed to explain human growth and aging."Rhythms"encompass not only circadian cycles but also the movement of qi and blood,as well as the contraction rhythm of muscle fascia,among other physiological processes."States"refer to the dynamic evolution and transformation of qi during the"opening-closing-pivot"stages in both time and space."Harmony"pertains not only to the individual physiological balance of"rhythms"or"states"but also to their coherent interaction.The fundamental cause of myopia is"the disharmony of rhythms and states",considering that rhythm disorders,qi and blood disorders,and fascia imbalances contribute to this disease.Based on this understanding,myopia prevention and treatment should center on"regulating rhythms and states",with adjusting the pivot to brighten the eyes as the core therapeutic principle throughout the entire cycle of myopia.Treatment should be tailored to different disease stages and supplemented with methods such as time-based regulation,qi and blood harmonization,tendon relaxation and collateral dredging,and essence and blood nourishment to prevent and manage myopia effectively.

Objective To analyze the efficacy of hepatic arterial infusion chemotherapy(HAIC)sequential drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)in the treatment of liver metastases from colorectal cancer.Methods 86 patients with colorectal cancer liver metastasis admitted to multiple centers from September 2022 to September 2023 were selected and divided into a control group(43 cases)and an experimental group(43 cases)according to the random number table method.The control group was treated with HAIC,and the experimental group was treated with HAIC sequential DEB-TACE.The clinical data and the changes of tumor markers and liver function indexes before and after treatment were compared between the two groups,and the short-term and long-term efficacy was evaluated,and the adverse reactions were recorded.Results After treatment,the levels of carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199,carbohydrate antigen 242,aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and γ-glutamyl transpeptidase in the two groups decreased(P<0.05),and those in the experimental group were lower than the control group(P<0.05).The proportion of repeated treatment in the experimental group was lower than that in the control group(P<0.05).The objective remission rate and disease control rate in the experimental group were 60.00%and 82.50%respectively,which were higher than 30.95%and 61.90%in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the control group and the experimental group(P>0.05).The results of Kaplan-Meier survival curve showed that the overall survival rate and progression-free survival rate of the experimental group were higher than those of the control group(P<0.05).Conclusions HAIC sequential DEB-TACE can effectively remove tumor cells and improve liver function in patients with colorectal can-cer liver metastasis,and it has good clinical efficacy and can prolong the survival time of patients.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Klebsiella pneumoniae,as a clinically prevalent opportunistic pathogen,ranks as the second most com-monly detected pathogen in clinical isolates in China.The extensive clinical use of carbapenem antibiotics has led to a high global detection rate of carbapenem-resistant K.pneumoniae(CRKP).Characterized by complex resist-ance mechanisms and diverse evolutionary pathways,CRKP infections pose significant challenges in prevention and treatment,with high associated mortality rates,creating substantial obstacles for clinical anti-infective therapy.In recent years,the emergence and global spread of carbapenem-resistant hypervirulent K.pneumoniae(CR-hvKP)have escalated into a major public health threat.Notably,hypervirulent K.pneumoniae isolates carry-ing carbapenem resistance genes are rapidly disseminating worldwide,causing fatal infections even in immunocom-petent individuals.This article systematically reviews the latest research advances on the resistance mechanisms,evolutionary pathways,adaptive changes,and clinical management strategies of CR-hvKP,aiming to deepen un-derstanding of this"superbug"and provide a theoretical foundation for clinical prevention and control.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Retinopathy caused by myopia is the first cause of irreversible blinding eye disease in China.The TCM methods to prevent and control myopia mainly include Chinese materia medica and TCM appropriate techniques,which have the advantages of good efficacy,simple operation,and few adverse reactions.This paper believed that internal and external pathogenic factors act on the brain and eyes,breaking their homeostasis,leading to rhythmic disorders,and imbalance of essence,qi and blood is the main pathogenesis of myopia.Based on the idea of"nature and human in the same rhythm"and"the same treatment for common diseases",targeting the above pathogenesis,the method of"brain-eye synchronization"was proposed to restore the homeostasis of the brain and eyes to prevent and control myopia in children and adolescents,and the treatment rules were to regulate the rhythms of the time,harmonize the qi and blood,nourish the blood to soften the tendons,and replenish the essence and blood,so as to achieve the effect of brain-eye synchronization and the treatment of the spirit and the body together.This article summarized the theoretical basis of"brain-eye synchronization"and its clinical application in traditional Chinese and Western medicine,with a view to providing new ideas for the prevention and control of myopia in children and adolescents.

Plant-derived bioactive peptides have become a research hotspot in the fields of food and medicine due to their high source safety,easy absorption and utilization by the human body,and potential edible and medicinal value.Bioactive peptides can be classified into antihypertensive,hypoglycemic,hypolipidemic,anticancer,antioxidant,antimicrobial,and anti-inflammatory peptides according to their functions.Among these,antihypertensive,hypoglycemic,and hypolipidemic peptides are collectively referred to as cardiovascular active peptides,which can be used for the treatment and prevention of cardiovascular diseases and have an important role in the development of modem biomedicine.This review focused on the preparation methods,separation,purification,and identification techniques of bioactive peptides,as well as their mechanisms of action and applications in regulating cardiovascular diseases,aiming to provide a reference for further development and application of plant-derived cardiovascular peptides.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.