Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Objective To compare the application value of direct arteriovenous fistula(AVF),after ultrasound-guided percutaneous transluminal angioplasty(PTA)dilation of radial artery AVF formation and reverse"J"arteriovenous graft(AVG)in hemodialysis patients with small diameter vessels.Methods Totally 96 end-stage renal disease patients with distal radial artery＜1.5 mm and cephalic vein≥2.0 mm who planning to receive hemodialysis were retrospectively enrolled.The patients were divided into AVF group(n=30),PTA+AVF group(n=34)and AVG group(n=32)according to fistulization methods.The technical success rate,clinical success rate,primary patency rate and secondary patency rate were compared among groups.Results The technical success rate of AVF group,PTA+AVF group and AVG group was 80.00%,94.12%and 100%,respectively,and the clinical success rate was 30.00%,82.35%and 93.75%,respectively,with significant differences among 3 groups(both P＜0.05).The primary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 80.00%,30.00%,27.59%,27.59%and 24.14%,respectively,in PTA+AVF group was 94.12%,82.35%,78.79%,68.75%and 62.50%,respectively,while in AVG group was 100%,93.33%,83.33%,76.67%and 66.67%,respectively,all being significant different among 3 groups(all P＜0.05).The secondary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 83.33%,75.00%,75.00%,70.83%and 58.33%,respectively,in PTA+AVF group was 93.33%,93.33%,83.33%,83.33%and 80.00%,respectively,while in AVG group was 100%,100%,93.33%,90.00%and 80.00%,respectively,also being significant different among 3 groups(all P＜0.05).Conclusion Compared with direct and after ultrasound-guided PTA dilation of radial artery AVF formation,AVG formation was more valuable for hemodialysis patients with small diameter vessels.

Objective To compare the application value of direct arteriovenous fistula(AVF),after ultrasound-guided percutaneous transluminal angioplasty(PTA)dilation of radial artery AVF formation and reverse"J"arteriovenous graft(AVG)in hemodialysis patients with small diameter vessels.Methods Totally 96 end-stage renal disease patients with distal radial artery＜1.5 mm and cephalic vein≥2.0 mm who planning to receive hemodialysis were retrospectively enrolled.The patients were divided into AVF group(n=30),PTA+AVF group(n=34)and AVG group(n=32)according to fistulization methods.The technical success rate,clinical success rate,primary patency rate and secondary patency rate were compared among groups.Results The technical success rate of AVF group,PTA+AVF group and AVG group was 80.00%,94.12%and 100%,respectively,and the clinical success rate was 30.00%,82.35%and 93.75%,respectively,with significant differences among 3 groups(both P＜0.05).The primary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 80.00%,30.00%,27.59%,27.59%and 24.14%,respectively,in PTA+AVF group was 94.12%,82.35%,78.79%,68.75%and 62.50%,respectively,while in AVG group was 100%,93.33%,83.33%,76.67%and 66.67%,respectively,all being significant different among 3 groups(all P＜0.05).The secondary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 83.33%,75.00%,75.00%,70.83%and 58.33%,respectively,in PTA+AVF group was 93.33%,93.33%,83.33%,83.33%and 80.00%,respectively,while in AVG group was 100%,100%,93.33%,90.00%and 80.00%,respectively,also being significant different among 3 groups(all P＜0.05).Conclusion Compared with direct and after ultrasound-guided PTA dilation of radial artery AVF formation,AVG formation was more valuable for hemodialysis patients with small diameter vessels.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.

Objective To determine whether Tanshinone ⅡA(Tan ⅡA)has an effect on angiotensin Ⅱ(Ang Ⅱ)-induced prolifera-tion and migration of vascular smooth muscle cells(VSMCs),phenotypic switching,or autophagy.Methods In this study,murine aortic smooth muscle cell lines were treated with Ang Ⅱ to establish a model of cell proliferation.Different concentrations of Tan ⅡA were added and effects on cell proliferation and migration were determined by cell counting using a CCK-8 assay and a cell scratch assay,respectively.Alpha-smooth muscle actin(α-SMA),a marker of contractile VSMCs,was detected by Western blotting.Expression levels of osteopontin(OPN)and the autophagy-related proteins(p62,Beclin-1,LC3A/B)were assayed to determine the effect of Tan ⅡA on VSMC phenotypic transformation and autophagy.Cells were treated with the autophagy inhibitor 3-methyladenine(3-MA),combined with Tan ⅡA,and then cell proliferation,migration and expression levels of phenotypic markers and autophagy-related proteins were assessed.Results After Ang Ⅱ treatment,the proliferation and migratory capacity of VSMCs was significantly enhanced,and phenotypic transformation was sig-nificantly inhibited by Ang Ⅱ.Western blotting revealed that Ang Ⅱ reduced the expression of α-SMA,increased the expression of OPN,p62,Beclin-1,and LC3A/B,and that these effects increased with higher Tan ⅡA concentrations.After the addition of 3-MA to the treated cells,the proliferation and migration of VSMCs induced by Ang Ⅱ was inhibited,the expression of α-SMA was increased,and the expres-sion of OPN,p62,Beclin-1,and LC3A/B was decreased,which was consistent with the effect of Tan ⅡA.Conclusion Tan ⅡA may have inhibitory effects on phenotypic transformation,proliferation,migration,and autophagy of Ang Ⅱ-treated VSMC,suggesting that the inhi-bition of the proliferation and migration may be regulated by autophagy.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective To retrieve,analyse and integrate the best evidences in perioperative fluid management for elderly patients with hip fracture,therefore to provide references for patient care.Methods Following the 6S evidence model,databases and websites were searched to collect the evidences on perioperative fluid management of elderly patients with hip fracture.The searched databases including BMJ Best Practice,UpToDate,AAOS Clinical Practice Guidelines,ASBMR,ANZHFR,ESTES,NICE,SIGN,JBI,Cochrane Library,CINAHL,Embase,PubMed,Web of Science,CNKI,Wanfang Data,VIP database,CEBM Database,Medive,China Science and Technology Journal Database,SinoMed,and other websites about orthopaedics.The searched literatures included guidelines,clinical decision-making,best practices,expert consensus and systematic reviews.The time span for the published literatures was from the inception of the databases and websites to August 2022.Two researchers independently completed quality evaluations of the retrieved literatures,as well as extraction,assessment and integration of the abstracted evidences.Results A total of 15 articles were included,they were 2 guidelines,3 clinical decision-makings,1 best practice,7 expert consensus,and 2 systematic reviews.Thirty pieces of evidence were summarised from 7 aspects,covering multidisciplinary team collaboration,dynamic assessment and monitoring of fluid status,fluid resuscitation,fluid management before and after the surgery and health education.Conclusions This study summarised the best evidences in perioperative fluid management for elderly patients with hip fracture.The evidences provide an evidence-based solution which will enable the healthcare workers to fully combine the clinical scenarios,evaluate changes in fluid volume status dynamically,develope personalised fluid management strategies and improve patient outcomes.

Objective:To explore the correlation between defecation disorders and diet in patients undergoing sphincter-preserving surgery for rectal cancer.Methods:This study was a cross-sectional survey. From 2021 to 2023, convenience sampling was used to select 159 patients with rectal cancer who underwent sphincter-preserving surgery at Peking University Third Hospital as participants. The General Information Questionnaire, Food Frequency Questionnaire, and Defecation Questionnaire were used for the survey.Results:The incidence of defecation disorders in 159 patients with rectal cancer after sphincter-preserving surgery was 74.2% (118/159), and the types of defecation disorders with high to low incidence were "frequent defecation (96/159, 60.4%) " "constipation (37/159, 23.3%) " "diarrhea (33/159, 20.8%) " and "fecal incontinence" (24/159, 15.1%). Diets were clustered into 9 categories (vegetables and fruits, carbohydrate staple foods, red meat foods, gas producing foods, dairy products, white meat foods, dessert foods, high-fat foods, and spicy and stimulating foods). Binomial Logistic regression analysis showed that red meat foods and gas producing foods were the influencing factors of frequent defecation ( P<0.05), red meat foods was the influencing factor of diarrhea ( P<0.05), and carbohydrate staple foods was the influencing factor of fecal incontinence ( P<0.05) . Conclusions:The incidence of defecation disorders in patients with rectal cancer after sphincter-preserving surgery is relatively high, and the intake of red meat foods, gas producing foods, and carbohydrate staple foods should be appropriately controlled. Clinical medical and nursing staff should pay close attention to the diet of elderly patients.