Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P＜0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P＜0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P＜0.05),while no significant difference was found between the CS+MT and CS+HT groups(P＞0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P＜0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P＜0.05),with the CS+MT group having the lowest body weight(P＜0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P＜0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P＜0.05),with the CS+MT and CS+HT groups showing the lowest levels(P＜0.05).No significant difference was found between the CS+MT and CS+HT groups(P＞0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P＜0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P＜0.05),with the CS+MT group showing the lowest AUC for OGTT(P＜0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P＜0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P＜0.05),with no significant differences in TC and LDL-C levels between these two groups(P＞0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.

Aim To investigate the role of mesence-phalic astrocyte-derived neurotrophic factor(MANF)in the inhibitory effect of rhynchophylline(Rhy)on the malignant biological behaviors of gastric cancer cells and its underlying regulatory mechanisms.Meth-ods SGC-7901 gastric cancer cells were transfected using adenovirus and liposome transfection techniques.The experimental groups included:Control group,Rhy group,Rhy+NC group(Rhy+adenovirus-transfected MANF-irrelevant fragment),Rhy+si-MANF group(Rhy+adenovirus-transfected MANF siRNA),Vec-tor group(empty vector),OVE-MANF group(recom-binant plasmid overexpressing MANF).After 24 hours of intervention,cell proliferation,apoptosis,migra-tion,and invasion were assessed using the MTT assay,Hoechst staining,and Transwell assays,respectively.The expressions of MANF,Cyclin D1,and cleaved caspase-3 proteins were measured using Western blot.NF-κB transcriptional activity was evaluated via a lucif-erase reporter assay.Results Compared to the control group,Rhy treatment significantly inhibited gastric cancer cell growth in a dose-dependent manner(P＜0.05),induced typical apoptotic morphological chan-ges,and increased the expression of MANF and cleaved caspase-3 proteins(P＜0.05),while reduc-ing Cyclin D1 protein expression and NF-κB transcrip-tional activity(P＜0.05).Additionally,Rhy treat-ment markedly decreased cell migration and invasion capabilities(P＜0.05).In comparison to the Rhy group,adenovirus-mediated transfection of MANF siR-NA suppressed apoptosis,promoted gastric cancer cell proliferation,migration,and invasion,inhibited MANF and cleaved caspase-3 expression(P＜0.05),and enhanced Cyclin D1 protein levels and NF-κB transcriptional activity(P＜0.05).Compared to the Vector group,OVE-MANF(overexpression of MANF)induced apoptosis,suppressed proliferation,invasion,and metastasis of gastric cancer cells,upregulated MANF and cleaved caspase-3 expression(P＜0.05),and inhibited Cyclin D1 protein levels and NF-κB tran-scriptional activity(P＜0.05).Conclusion Rhy in-hibits the proliferation,migration,and invasion of gas-tric cancer cells and induces apoptosis,with its mecha-nism linked to the promotion of MANF expression and suppression of NF-κB transcriptional activity.

Multiple myeloma(MM)is a hematologic malignancy characterized by clonal proliferation of plasma cells within the bone marrow,with pathological features including abnormal secretion of mono-clonal immunoglobulins,osteolytic bone disease,and multi-organ dysfunction.Despite significant ad-vancements in therapeutic approaches that have markedly extended patient survival,primary drug resist-ance and relapse remain major obstacles to clinical cure.The pathogenesis and progression of MM are in-tricately regulated by the bone marrow microenvironment(BMME),a dynamic network composed of di-verse cellular and non-cellular components.The BMME not only supports the survival and proliferation of MM cells but also plays a pivotal role in disease progression by modulating bone metabolic homeostasis,mediating immune escape,and promoting drug resistance.In recent years,groundbreaking therapeutic strategies targeting the BMME have emerged,including immunomodulatory drugs,bispecific antibodies,CAR T-cell therapies,and microenvironment-modulating agents.These approaches have significantly im-proved objective response rates and survival outcomes in relapsed/refractory MM by disrupting cytokine signaling,reprogramming the immunosuppressive microenvironment,or inhibiting tumor-stromal interac-tions.However,challenges such as drug resistance,treatment-related toxicity,and tumor heterogeneity persist in clinical practice.This review systematically delineates the roles of BMME components in MM pathogenesis,analyzes the molecular mechanisms underlying MM cell-BMME interactions,and explores innovative strategies to enhance therapeutic efficacy and prognosis through targeted modulation of the BMME.These insights provide a foundation for developing novel therapeutic paradigms aimed at overco-ming current limitations in MM treatment.

CRY1/2,as important transcriptional regulators of the circadian clock system,play a crucial role in maintaining metabolic homeostasis in body.This article analyzes existing re-search and focuses on the regulatory mechanisms of CRY1/2 in glucose and lipid metabolism.CRY1 plays an important regula-tory role in gluconeogenesis,glycolysis and insulin secretion,maintaining blood glucose homeostasis by regulating the expres-sion of key enzymes.Additionally,CRY1/2 regulate lipid me-tabolism by modulating fat synthesis and absorption,thereby af-fecting energy balance in the body.This article also discuss the potential applications of CRY1/2 in obesity and xenobiotic de-toxification,highlighting their potential value as therapeutic tar-gets.As core factors in metabolic regulation,CRY1/2 have sig-nificant clinical application prospects,and a deeper understand-ing of their molecular mechanisms in glucose and lipid metabo-lism will provide new ideas and strategies for the treatment of chronic metabolic diseases.

Molecular biology experimental skills have become essential for medical and pharmaceutical undergraduates engaged in scientific research practice.To meet the training needs of molecular biology skills in different disciplines and majors,this study establishes a cross-major,cross-disciplinary,and cross-nationality scientific research mutual assistance group.The training of molecular biology experimen-tal skills was combined with a large-scale senior thesis design,where students collectively practiced and mastered a variety of molecular biology skills such as polymerase chain reaction,protein immunoblotting,and enzyme-linked immunosorbent assay in a comprehensive experiment.The implementation of this sci-entific research mutual assistance group model received positive feedbacks from students,who found that their molecular biology skills had significantly improved.The scores of the 'Molecular Biology' exam for the pharmaceutical and biological science major members of the research group were 80.7 and 72.5,re-spectively,which were significantly higher than the average scores of 74.77 and 67.26 for the same ma-jors.The comprehensive ability of students in molecular biology was enhanced.Multiple members of the research group participated in provincial biopharmaceutical skill competitions and won several second and third prizes.They were successfully funded for six undergraduate innovation and entrepreneurship pro-jects,including one provincial-level and five university-level projects,thus effectively improving students' scientific research and innovation capabilities.The thesis defense score of the research group members was 86.12,significantly higher than the average score of 83.43 for all members of the same de-fense group,indicating a significant improvement in students' senior thesis design level and comprehen-sive quality.The rate of the research group members to continue their graduate school study was 90％,significantly higher than the average enrollment rate of 38.61％for the same defense group.Taken to-gether,the establishment of a multidisciplinary cross-research mutual assistance group based on senior thesis optimized teaching resources,integrated teaching advantages,and effectively improved undergradu-ates' molecular biology experimental skills and scientific research skills.

Acquired resistance to the proteasome inhibitor bortezomib(BTZ)poses a significant chal-lenge in the treatment of multiple myeloma(MM).During the acquisition of BTZ resistance,metabolic reprogramming is actively engaged in MM cells.However,the key regulatory genes and molecular mecha-nisms mediating bortezomib resistance through this metabolic rewiring have not been fully elucidated.This study aims to investigate the regulatory role of pyrimidine metabolites in drug resistance of MM and their underlying molecular mechanisms.Screening via CCK-8 assays demonstrated that the pyrimidine metabolite uridine is associated with BTZ resistance in MM(P＜0.05).In vitro experiments,including CCK-8 assays,Western blotting,and flow cytometry,demonstrated that uridine partially suppresses bort-ezomib-induced apoptosis in MM cells(P＜0.05).In vivo,experiments utilizing Vk*MYC mouse mod-els,subcutaneous tumor models,and intramedullary bone marrow transplantation models showed that the combination of BTZ and uridine significantly accelerated tumor growth,exacerbated bone destruction,and increased tumor cell infiltration in tumor-bearing mice(P＜0.05).RNA sequencing analysis re-vealed that uridine primarily affects mitochondrial translation in MM at the transcriptional level.Seahorse energy metabolism assays demonstrated that uridine enhances mitochondrial oxidative phosphorylation without significantly altering glycolysis.Transcriptomic analysis further identified a significant upregula-tion of cytochrome c oxidase subunit 5B(COX5B)transcription in uridine-treated groups(P＜0.05).Functional studies confirmed that COX5B is a key molecule mediating uridine's effects on mitochondrial function in MM cells.In conclusion,uridine promotes BTZ resistance in MM by upregulating COX5B transcription and protein expression,thereby enhancing cytochrome c oxidase activity and regulating mito-chondrial oxidative phosphorylation.This study delineates the role of uridine in the development of borte-zomib resistance in MM and elucidates its COX5B-mediated metabolic reprogramming mechanism,provi-ding a theoretical foundation for developing targeted therapies against relapsed/refractory MM.

Multiple myeloma(MM)is the second most common hematological malignancy,predominant-ly affecting the elderly.With the development of an aging society in China,the incidence of MM has been steadily increasing,becoming a significant concern for public health and a considerable socioeco-nomic burden.Over the past two decades,breakthroughs have been achieved in both clinical manage-ment and basic research on MM.However,the field now stands at a crossroads for the next phase,facing numerous developmental directions and challenges.

Mesenchymal stem cells(MSCs)induces fusion of multiple monocyte macrophages by secre-ting key cytokines such as receptor activator for nuclear factor-κB ligand(RANKL)and macrophage CSF(M-CSF)to form multinucleated macrophages thereby SUMO-specific protease 3(SENP3)modifies pro-teins by de-SUMOylation,which in turn affects the stability,localization and activity of substrate pro-teins.Based on the previous work in our laboratory,we found that the number of osteoclasts increased in mice with SENP3 knockdown in MSC(***P＜0.001).To further explore the mechanism,using immuno-fluorescence as well as Western blotting assay,we found that knockdown of the Hedgehog(Hh)signaling pathway by SENP3 increased the transcription factor glioma-associated oncogene homolog 2(Gli2),which is the most important transcription factor for the production of osteoclasts.CHIP-qPCR results showed that Gli2 promoted COX2 transcription by binding to cyclooxygenase-2(COX2)promoter regions-1 235～-1 249 and-1 158～-1 172(*P＜0.05);meanwhile,the main secretion product of COX2,pep-tide,was detected by ELISA(*P＜0.05).The level of prostaglandin E2(PGE2),the main secretory product of COX2,was increased in the supernatant of the culture medium of MSC with knockdown of SENP3 by ELISA(***P＜0.001).PGE2 is known to mediate cell migration and osteoclastogenesis through E-type prostanoid receptor 2(EP2)and E-type prostanoid receptor 4(EP4).In the study,the expression of EP4 receptor was found to be elevated in differentiated osteoclasts(**P＜0.01).The inhib-itors of the EP4 receptor significantly reduced the expression of nuclear factor-activated T cell 1(NFATc1),Cathepsin K(Ctsk),and tartrate resistant acid phosphatase(TRAP)genes(*P＜0.05)and decreased osteoclastogenesis(***P＜0.001),suggesting that EP4 receptors play a critical role in PGE2-mediated osteoclast differentiation.In conclusion,SENP3 deletion in mouse MSCs promotes COX2 transcription and PGE2 secretion through activation of the Hh signaling pathway thereby promoting osteo-clast formation.