[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

Objective The study aims to elucidate the inhibitory effects of curcumin on the proliferation of colon cancer RKO cells,focusing on the regulatory mechanisms of tripartite motif-containing protein 2(TRIM2)expression and the mammalian target of rapamycin(mTOR)signaling pathway.Methods Experimental concentrations of curcumin were determined by calculating the half maximal inhibitory concentration(IC50)value.Quantitative polymerase chain reaction(qPCR)was utilized to assess the level of TRIM2 expression in RKO and fetal human colon(FHC)cells.Western blotting analysis was conducted to investigate the level of TRIM2 expression and mTOR pathway-related proteins in curcumin-treated RKO cells.The impact of curcumin treatment,TRIM2-knockingdown,and mTOR signaling pathway on proliferation in RKO cells was quantified using the cell counting kit-8(CCK8)assay.Results The expression of TRIM2 was found to be elevated in RKO cells as determined by qPCR,compared to FHC cells.Curcumin suppressed the level of TRIM2 expression,and subsequent knockdown of TRIM2 resulted in decreased expression of mTOR-related proteins in RKO cells.Both curcumin and TRIM2-knockdown demonstrated significant inhibition of proliferation in RKO cells,with reversion upon activation of mTOR signaling pathway.Conclusion The study unveils the inhibitory effects of curcumin on RKO cells proliferation through modulation of TRIM2 expression and the mTOR signaling pathway.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

Dental stem cells(DSCs),a distinct subset of mesenchymal stem cells(MSCs),are isola-ted from dental tissues,such as dental pulp,exfoliated deciduous teeth,periodontal ligament,and apical papilla.They have emerged as a promising source of stem cell therapy for tissue regeneration and autoim-mune disorders.The main types of DSCs include dental pulp stem cells(DPSCs),stem cells from hu-man exfoliated deciduous teeth(SHED),periodontal ligament stem cells(PDLSCs),and stem cells from apical papilla(SC AP).Each type exhibits distinct advantages:easy access via minimally invasive procedures,multi-lineage differentiation potential,and excellent ethical acceptability.DSCs have demon-strated outstanding clinical efficacy in oral and maxillofacial regeneration,and their long-term safety has been verified.In oral tissue regeneration,DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair.A defining advan-tage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration,which render them a better option for oral tissue regenerative therapies.Beyond oral applications,DSCs also exhibit promising potential in the treatment of systemic diseases,including type Ⅱ diabetes and au-toimmune diseases due to their immunomodulatory effects.Moreover,extracellular vesicles(EVs)de-rived from DSCs act as critical mediators for DSCs' paracrine functions.Possessing regulatory properties similar to their parental cells,EVs are extensively utilized in research targeting tissue repair,immuno-modulation,and regenerative therapy—offering a"cell-free"strategy to mitigate the limitations associated with cell-based therapies.Despite these advancements,standardizing large-scale manufacturing,maintai-ning strict quality control,and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use.Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy.In conclusion,DSCs and their EVs represent a transformative approach in re-generative medicine,and increasing clinical evidence supports their application in oral and systemic diseases.Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.

Objective To compare the complications,etiology,and clinical manifestations between pediatric patients with heart valve disease undergoing surgical treatment.Methods A retrospective analysis was conducted on the clinical data of 169 pediatric patients aged 0-14 years diagnosed with heart valve abnormalities at Wuhan Union Hospital from January 2019 to October 2022.Patients were divided into two groups based on whether they received surgical intervention for valve abnormali-ties:the surgical treatment group and the medical treatment group.Results There were significant differences in age,type and grade of heart failure,club-finger,pneumonia and cough,cardiac morphology,arrhythmia,ventricular septal width and left ven-tricular ejection fraction(all P＜0.05).Univariate and multivariate binary logistic regression analyses revealed that left ventricu-lar ejection fraction(OR=1.206,95％CI:1.072-1.357,P＜0.05)was an independent risk factor for the surgical treatment group.Conclusion The clinical manifestations of heart valve abnormalities in children are often atypical.Clinicians should ac-tively evaluate the etiology based on clinical symptoms and echocardiographic findings,and develop individualized treatment strategies,either surgical or medical,to prevent the progression of severe heart disease.

Objective The study aims to elucidate the inhibitory effects of curcumin on the proliferation of colon cancer RKO cells,focusing on the regulatory mechanisms of tripartite motif-containing protein 2(TRIM2)expression and the mammalian target of rapamycin(mTOR)signaling pathway.Methods Experimental concentrations of curcumin were determined by calculating the half maximal inhibitory concentration(IC50)value.Quantitative polymerase chain reaction(qPCR)was utilized to assess the level of TRIM2 expression in RKO and fetal human colon(FHC)cells.Western blotting analysis was conducted to investigate the level of TRIM2 expression and mTOR pathway-related proteins in curcumin-treated RKO cells.The impact of curcumin treatment,TRIM2-knockingdown,and mTOR signaling pathway on proliferation in RKO cells was quantified using the cell counting kit-8(CCK8)assay.Results The expression of TRIM2 was found to be elevated in RKO cells as determined by qPCR,compared to FHC cells.Curcumin suppressed the level of TRIM2 expression,and subsequent knockdown of TRIM2 resulted in decreased expression of mTOR-related proteins in RKO cells.Both curcumin and TRIM2-knockdown demonstrated significant inhibition of proliferation in RKO cells,with reversion upon activation of mTOR signaling pathway.Conclusion The study unveils the inhibitory effects of curcumin on RKO cells proliferation through modulation of TRIM2 expression and the mTOR signaling pathway.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

Background and Amis:Gallbladder cancer(GBC)is the most common malignant tumor of the biliary tract,accounting for approximately 80%-95%of biliary tract cancers.This type of tumor has a poor prognosis,and currently,there are no effective tools for evaluating the prognosis of GBC.Therefore,this study was performed to investigate the factors influencing the prognosis of GBC patients to provide a reference for clinical practice.Methods:The clinical data and follow-up information from 160 GBC patients treated in the Hunan Provincial People's Hospital from January 2018 to January 2024 was retrospectively conducted.The clinicopathologic characteristics of GBC patients were analyzed.Kaplan-Meier and Log-rank tests were used to calculate and compare the differences in overall survival(OS)among GBC patients with different clinicopathologic characteristics and treatment methods.Multivariate analysis using Cox regression was performed to identify independent prognostic factors for GBC.Results:Among the 160 patients,113 were females and 47 were males.The median age of the patients was 62 years,with the main clinical manifestations being abdominal pain/distention(55.63%),jaundice(40.63%),appetite loss(30.62%),and weight loss(19.38%).Serum tumor markers,including CA19-9,CA125,CEA,and CA724,were elevated in 58.75%,30.63%,30.00%,and 20.63%of GBC patients,respectively.Clinical stage classification revealed that 139 patients(86.87%)had stage Ⅲ/Ⅳ disease,132 patients(82.5%)had T3/T4 stage,91 patients(56.87%)had N1/N2 stage,and 54 patients(33.75%)had M1 stage.The pathological type of GBC was predominantly adenocarcinoma(92.50%),with the majority classified as moderately differentiated(19.38%),moderately to poorly differentiated(34.37%),and poorly differentiated(24.37%).Neural or vascular invasion was present in 29.37%and 21.25%of patients,respectively.Univariate analysis showed that diabetes,jaundice,liver function(Child-Pugh classification),tumor marker levels(CA19-9,CA125,CEA,CA724,CYFRA 21-1),clinical TNM stage,degree of differentiation,vascular or neural invasion,surgical treatment,and other treatments(chemotherapy,immunotherapy,targeted therapy,traditional Chinese medicine,etc.)were significantly associated with the prognosis of GBC patients(all P<0.05).Multivariate Cox regression analysis revealed that diabetes,elevated CA125,and TNM stage were independent risk factors for poor prognosis in GBC,while chemotherapy-based drug treatment was an independent protective factor(all P<0.05).Conclusion:Diabetes,elevated CA125,TNM staging,and treatment methods are closely related to the prognosis of GBC patients.Targeted treatment strategies should be developed for patients with risk factors,and surgery or chemotherapy-based drug therapy should be prioritized to improve patient prognosis.

Background and Amis:Gallbladder cancer(GBC)is the most common malignant tumor of the biliary tract,accounting for approximately 80%-95%of biliary tract cancers.This type of tumor has a poor prognosis,and currently,there are no effective tools for evaluating the prognosis of GBC.Therefore,this study was performed to investigate the factors influencing the prognosis of GBC patients to provide a reference for clinical practice.Methods:The clinical data and follow-up information from 160 GBC patients treated in the Hunan Provincial People's Hospital from January 2018 to January 2024 was retrospectively conducted.The clinicopathologic characteristics of GBC patients were analyzed.Kaplan-Meier and Log-rank tests were used to calculate and compare the differences in overall survival(OS)among GBC patients with different clinicopathologic characteristics and treatment methods.Multivariate analysis using Cox regression was performed to identify independent prognostic factors for GBC.Results:Among the 160 patients,113 were females and 47 were males.The median age of the patients was 62 years,with the main clinical manifestations being abdominal pain/distention(55.63%),jaundice(40.63%),appetite loss(30.62%),and weight loss(19.38%).Serum tumor markers,including CA19-9,CA125,CEA,and CA724,were elevated in 58.75%,30.63%,30.00%,and 20.63%of GBC patients,respectively.Clinical stage classification revealed that 139 patients(86.87%)had stage Ⅲ/Ⅳ disease,132 patients(82.5%)had T3/T4 stage,91 patients(56.87%)had N1/N2 stage,and 54 patients(33.75%)had M1 stage.The pathological type of GBC was predominantly adenocarcinoma(92.50%),with the majority classified as moderately differentiated(19.38%),moderately to poorly differentiated(34.37%),and poorly differentiated(24.37%).Neural or vascular invasion was present in 29.37%and 21.25%of patients,respectively.Univariate analysis showed that diabetes,jaundice,liver function(Child-Pugh classification),tumor marker levels(CA19-9,CA125,CEA,CA724,CYFRA 21-1),clinical TNM stage,degree of differentiation,vascular or neural invasion,surgical treatment,and other treatments(chemotherapy,immunotherapy,targeted therapy,traditional Chinese medicine,etc.)were significantly associated with the prognosis of GBC patients(all P<0.05).Multivariate Cox regression analysis revealed that diabetes,elevated CA125,and TNM stage were independent risk factors for poor prognosis in GBC,while chemotherapy-based drug treatment was an independent protective factor(all P<0.05).Conclusion:Diabetes,elevated CA125,TNM staging,and treatment methods are closely related to the prognosis of GBC patients.Targeted treatment strategies should be developed for patients with risk factors,and surgery or chemotherapy-based drug therapy should be prioritized to improve patient prognosis.