Pancreatic cancer is characterized by significant drug resistance,and despite continuous advancements in treatment regimens,the 5-year survival rate of patients remains low.The nuclear factor-κB(NF-κB)signaling pathway,frequently mutated in tumors,has been identified as a critical factor in triggering drug resistance.Multiple studies have demonstrated that strategies targeting NF-κB signaling transduction exhibit promising outcomes in pancreatic cancer treatment.Therefore,exploring the relationship between the NF-κB signaling pathway and drug resistance in pancreatic cancer has become a research hotspot in pancreatic cancer treatment.This review summarizes recent advances in the relationship between NF-κB signaling pathway and tumor drug resistance,as well as its role in pancreatic cancer treatment.Specifically,the mechanisms by which the NF-κB signaling pathway mediates drug resistance in pancreatic cancer are elaborated from two perspectives:chemotherapy and immunotherapy,aiming to provide insights for pancreatic cancer treatment and future research.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To analyze the relationship between cuprotosis-realted gene DLD expression in pan-cancer and progno-sis,tumor microenvironment and tumor immune infiltration by bioinformatics methods combined with multiple databases.Methods:TCGA,GTEx,TISDB,GEO,UCSC,TARGET,TIMER2.0,GEPIA2,SangerBox,PrognoScan and related R software packages were used to analyze the difference of DLD expression between human cancer and adjacent normal tissues,inestigate relationship between prognosis,explore expression of DLD in different immune subtypes and molecular subtypes of human cancer,analyze correlation between DLD expression and tumor immune infiltration and tumor microenvironment,detecet relationship between DLD expression and 60 immune checkpoint genes.Results:There were differences in expression of DLD in different tumor tissues;low DLD expression in 6 tumors and high DLD expression in 3 tumors were significantly associated with better prognosis;15 tumor immune subtypes,11 molecular subtypes of tumors were significantly correlated with DLD expression;DLD expression was significantly correlated with immune infiltration in 37 cancer types;DLD expression was significantly associated with immune infiltration in 23 tumor stroma scores,26 tumor immune scores and 25 tumor ESTIMATE scores;60 immune checkpoint genes in 39 tumors were significantly associated with DLD expression.Conclusion:Expression of DLD in pan-cancer is related to tumor prognosis and immune invasion,DLD may be a potential predictor of prognosis in tumors,and may be an immunomodulator of tumors.

Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P＜0.01)and lower body weight(P＜0.05);the level of FTO protein in aorta of DM group increased(P＜0.01),and the level of m6A methylation modification decreased(P＜0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P＜0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P＜0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P＜0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.

This case report highlights the successful treatment of moderate-to-severe thyroid-associated ophthalmopathy(TAO) with teprotumumab in a patient who had previously failed multiple therapies, including intravenous steroid pulse therapy, local thyroid injections of cyclophosphamide, octreotide and dexamethasone, tocilizumab treatment, total thyroidectomy, and orbital radiation. Despite these interventions, there was no improvement in TAO. Following treatment with teprotumumab, the patient experienced a reduction of 5 mm in left eye proptosis and 4 mm in right eye proptosis, a 6-point decrease in the clinical activity score(CAS), a 2-point reduction in the diplopia score, and a significant improvement in quality of life, with sustained effects lasting 72 weeks. The treatment was well tolerated, with mild side effects including muscle spasm, fatigue, and dryness of the skin and nasal mucosa. This case report aims to raise clinical awareness regarding efficacy and safety of teprotumumab.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

OBJECTIVE To investigate the therapeutic mechanisms of electroacupuncture at"Tianshu"(ST25)and"Sanyinjiao"(SP6)acupoints combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)using serum non-targeted metabolomics.METHODS Male SD rats were randomly divided into blank group,model group,metformin group,electroacupunc-ture group,and acupuncture-medicine combination(electroacupuncture combined with metformin)group.A type 2 diabetes model was established by high-fat diet combined with intraperitoneal injection of streptozotocin.The metformin group was treated with 250 mg·kg-1 metformin by gavage,the electroacupuncture group was treated with bilateral Tianshu and Sanyinjiao,the acupuncture-medicine combination group was treated with metformin by gavage combined with electroacupuncture,and the blank group and model group were treated with normal saline by gavage.All rats were treated 6 times a week for 7 weeks.After the intervention,the blood glucose level in the tail vein of the rats was measured using a blood glucose meter in the fasting state.The blood glucose levels of the rats were measured at 30,60,120,and 240 min after intraperitoneal injection of 50%glucose solution(4 mL·kg-1)to evaluate glu-cose tolerance.The serum insulin level of the rats was detected by ELISA and the insulin resistance index was calculated.The blood biochemical parameters were measured by an automatic blood biochemical analyzer.HE staining was used to evaluate the pathological conditions of the liver and pancreatic tissues of the rats.Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was used for mass spectrometry detection to identify differential metabolites,and MetaboAnalyst 5.0 was used for pathway enrichment analysis.RESULTS Compared with the blank group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the model group rats were significantly increased(P<0.001),blood TP and GLB were significantly de-creased(P<0.01),AST,ALT,and ALP were significantly increased(P<0.05,P<0.01,P<0.001),and obvious inflammatory cell infiltration and pathological damage were observed in the liver and pancreas tissues;compared with the model group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the acupuncture-medicine combination group were sig-nificantly decreased(P<0.05,P<0.01,P<0.001),blood ALP was significantly decreased(P<0.01),TP and GLB were significant-ly increased(P<0.05),and the pathological damage of the liver and pancreas was significantly improved.Serum metabolomics showed that the metabolic profiles of the groups were well distinguished.Compared with the blank group,the differential metabolites in the model group were enriched in histidine metabolism,thiamine metabolism,taurine and hypotaurine metabolism,ascorbic acid and alde-hyde ester metabolism,valine,leucine and isoleucine biosynthesis pathways;compared with the model group,237 metabolites such as 3-aminoadipic acid,3-oxocyclobutanecarboxylic acid and phosphorylcholine in the acupuncture-medicine combination group were sig-nificantly reduced,and the pathways were enriched in histidine metabolism,linoleic acid metabolism,thiamine metabolism,taurine and hypotaurine metabolism,valine,leucine and isoleucine biosynthesis pathways.CONCLUSION Electroacupuncture combined with metformin can effectively improve the glucose and lipid metabolism of T2DM rats,and its potential mechanism may be related to the regulation of amino acid metabolism.