[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Objective The purpose of this study was to provide a more effective method for researching the prevention and treatment of Graves'disease by comparing the effects of two plasmid vectors expressing the human thyrotropin receptor(TSHR)A subunit gene in inducing an animal model of Graves'disease via electroporation.Methods Plasmids pcDNA3.1-THSR A,and pTriEx1.1-THSR A expressing the TSHR A subunit were constructed and used to induce Graves'disease by intramuscular injection with immediate electroporation once every 3 weeks for a total of 4 times.Mice in the control group were injected with PBS.One week after the second electroporation,blood was collected to measure serum thyrotropin receptor antibody(TRAb).Three weeks following the last electroporation,echocardiography was performed on the mice.Mice were sacrificed 4 weeks after the last electroporation;blood,thyroid,and orbital tissues were collected;serum total thyroxine(TT4)was measured;and histological examination was performed.Results The average concentrations of serum TRAb in the pcDNA3.1-TSHR A group(n=15)and the pTriEx1.1-TSHR A group(n=13)were(6.9±2.0)U/L and(7.5±2.2)U/L,respectively.The latter was significantly higher than that in the control group(4.9±0.5)U/L(P=0.033).The average concentrations of serum TT4 in the pcDNA3.1-TSHR A group and pTriEx1.1-TSHR A group were(41.4±23.8)ng/mL and(63.2±53.7)ng/mL,respectively,both higher than that in the control group:(20.2±4.0)ng/mL(P＜0.01).Thyroid pathology showed thyroid follicular epithelial hyperplasia with T-cell infiltration in the model group.Echocardiography showed that the left ventricle mass in the pTriEx1.1-TSHR A group was higher than those in the control group(P=0.007)and pcDNA3.1-TSHR A group(P=0.012).Orbital pathology showed fibrotic changes in the extraocular muscles of mice in the model groups.Conclusions Both pcDNA3.1 and pTriEx1.1 expressing the TSHR A subunit were able to induce Graves'disease in mice by electroporation,and the efficiency of the two plasmids in inducing hyperthyroidism and Graves'ophthalmopathy was similar.The efficiency of pTriEx 1.1-TSHR A in inducing thyrotoxic heart disease was better than that of pcDNA3.1-TSHR A.

Objective To explore the value of preoperative amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in predicting lymphovascular space invasion(LVSI)in cervical cancer.Methods Fifty-one patients with cervical cancer who underwent preoperative MRI examination and had complete postoperative pathology were retrospectively selected.Pelvic MRI scans were performed 1-2 weeks preoperatively,and the corresponding APT values,mean kurtosis(MK)and mean diffusivity(MD)values were obtained respectively,and the occurrence of LVSI was determined based on postoperative pathology results.The predictive effects of APT-and DKI-derived parameters alone or in combination on the LVSI status of cervical cancer were compared.Results Among 51 cases of cervical cancer,36 cases had pathologically confirmed LVSI and 15 cases did not had LVSI.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve for the preoperative APT values,MK and MD values alone and in combination to predict the LVSI status of cervical cancer were 0.820,0.788,0.762,0.894,0.885,and 0.896,respectively.APT values combined with DKI-derived parameters predicted LVSI better than when they were used separately,in which APT values combined with MK and MD values predicted LVSI of cervical cancer with the largest AUC,sensitivity of 91.7％,specificity of 80.0％,and Youden's index of 0.717.Conclusion Preoperative APT imaging and DKI have important value in predicting LVSI of cervical cancer,and the combined application of the two can improve the prediction efficacy,which has certain clinical application value.

Objective:To investigate the effects of electroacupuncture stimulation on the expression of Nrf2 and GPX4 proteins in the hippocampal CA1 region of rats with middle cerebral artery occlusion(MCAO)and its neuroprotective mechanism.Methods:Forty-eight rats were divided into the normal group(Normal),the sham operation control group(Sham),the model group(MCAO)and the electroacupuncture group(EA)according to the random number table method.The right middle cerebral artery occlusion model was established in the MCAO and EA groups by the modified thread embolization method.Starting on day 1 post-modeling,the EA group received electroacupuncture stimulation at the"Baihui"point(GV20)and left"Neiguan"point(PC6)for 30 min daily over 14 d.The Normal group received no treatment,and the Sham group only underwent vascular isolation without inserting the suture.Neurological function of rats in each group were scored before and after modeling and before and after electroacupuncture stimulation using the Zea Longa scoring scale.The structure and arrangement of Nissl-positive cells in the hippocampal CA1 region were observed by Nissl staining.Western blot and immunohistochemical staining were used to determine the expression levels of Nrf2 and GPX4 proteins in the hippocampal CA1 region.Results:Compared with the Normal group,the Sham group showed no neurological deficits,abundant Nissl-positive cells,and no statistically significant differences in Nrf2 and GPX4 protein expression or positive cell counts.Compared with the Sham group,the MCAO group exhibited elevated Zea Longa score,reduced Nissl-positive cell counts,and decreased Nrf2 and GPX4 protein expression and positive cell counts(P＜0.05).In contrast,the EA group demonstrated lower Zea Longa scores,increased Nissl-positive cell counts,and elevated Nrf2 and GPX4 protein expression and positive cell counts compared to the MCAO group(P＜0.05).Conclusion:Electroacupuncture stimulation may protect against neuronal damage in the hippocampal CA1 region of MCAO rats,potentially through up-regulation of Nrf2 and GPX4 expression.

Objective:To investigate the effects of electroacupuncture stimulation on the expression of Nrf2 and GPX4 proteins in the hippocampal CA1 region of rats with middle cerebral artery occlusion(MCAO)and its neuroprotective mechanism.Methods:Forty-eight rats were divided into the normal group(Normal),the sham operation control group(Sham),the model group(MCAO)and the electroacupuncture group(EA)according to the random number table method.The right middle cerebral artery occlusion model was established in the MCAO and EA groups by the modified thread embolization method.Starting on day 1 post-modeling,the EA group received electroacupuncture stimulation at the"Baihui"point(GV20)and left"Neiguan"point(PC6)for 30 min daily over 14 d.The Normal group received no treatment,and the Sham group only underwent vascular isolation without inserting the suture.Neurological function of rats in each group were scored before and after modeling and before and after electroacupuncture stimulation using the Zea Longa scoring scale.The structure and arrangement of Nissl-positive cells in the hippocampal CA1 region were observed by Nissl staining.Western blot and immunohistochemical staining were used to determine the expression levels of Nrf2 and GPX4 proteins in the hippocampal CA1 region.Results:Compared with the Normal group,the Sham group showed no neurological deficits,abundant Nissl-positive cells,and no statistically significant differences in Nrf2 and GPX4 protein expression or positive cell counts.Compared with the Sham group,the MCAO group exhibited elevated Zea Longa score,reduced Nissl-positive cell counts,and decreased Nrf2 and GPX4 protein expression and positive cell counts(P＜0.05).In contrast,the EA group demonstrated lower Zea Longa scores,increased Nissl-positive cell counts,and elevated Nrf2 and GPX4 protein expression and positive cell counts compared to the MCAO group(P＜0.05).Conclusion:Electroacupuncture stimulation may protect against neuronal damage in the hippocampal CA1 region of MCAO rats,potentially through up-regulation of Nrf2 and GPX4 expression.

Objective The purpose of this study was to provide a more effective method for researching the prevention and treatment of Graves'disease by comparing the effects of two plasmid vectors expressing the human thyrotropin receptor(TSHR)A subunit gene in inducing an animal model of Graves'disease via electroporation.Methods Plasmids pcDNA3.1-THSR A,and pTriEx1.1-THSR A expressing the TSHR A subunit were constructed and used to induce Graves'disease by intramuscular injection with immediate electroporation once every 3 weeks for a total of 4 times.Mice in the control group were injected with PBS.One week after the second electroporation,blood was collected to measure serum thyrotropin receptor antibody(TRAb).Three weeks following the last electroporation,echocardiography was performed on the mice.Mice were sacrificed 4 weeks after the last electroporation;blood,thyroid,and orbital tissues were collected;serum total thyroxine(TT4)was measured;and histological examination was performed.Results The average concentrations of serum TRAb in the pcDNA3.1-TSHR A group(n=15)and the pTriEx1.1-TSHR A group(n=13)were(6.9±2.0)U/L and(7.5±2.2)U/L,respectively.The latter was significantly higher than that in the control group(4.9±0.5)U/L(P=0.033).The average concentrations of serum TT4 in the pcDNA3.1-TSHR A group and pTriEx1.1-TSHR A group were(41.4±23.8)ng/mL and(63.2±53.7)ng/mL,respectively,both higher than that in the control group:(20.2±4.0)ng/mL(P＜0.01).Thyroid pathology showed thyroid follicular epithelial hyperplasia with T-cell infiltration in the model group.Echocardiography showed that the left ventricle mass in the pTriEx1.1-TSHR A group was higher than those in the control group(P=0.007)and pcDNA3.1-TSHR A group(P=0.012).Orbital pathology showed fibrotic changes in the extraocular muscles of mice in the model groups.Conclusions Both pcDNA3.1 and pTriEx1.1 expressing the TSHR A subunit were able to induce Graves'disease in mice by electroporation,and the efficiency of the two plasmids in inducing hyperthyroidism and Graves'ophthalmopathy was similar.The efficiency of pTriEx 1.1-TSHR A in inducing thyrotoxic heart disease was better than that of pcDNA3.1-TSHR A.

Objective To explore the value of preoperative amide proton transfer(APT)imaging combined with diffusion kurtosis imaging(DKI)in predicting lymphovascular space invasion(LVSI)in cervical cancer.Methods Fifty-one patients with cervical cancer who underwent preoperative MRI examination and had complete postoperative pathology were retrospectively selected.Pelvic MRI scans were performed 1-2 weeks preoperatively,and the corresponding APT values,mean kurtosis(MK)and mean diffusivity(MD)values were obtained respectively,and the occurrence of LVSI was determined based on postoperative pathology results.The predictive effects of APT-and DKI-derived parameters alone or in combination on the LVSI status of cervical cancer were compared.Results Among 51 cases of cervical cancer,36 cases had pathologically confirmed LVSI and 15 cases did not had LVSI.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve for the preoperative APT values,MK and MD values alone and in combination to predict the LVSI status of cervical cancer were 0.820,0.788,0.762,0.894,0.885,and 0.896,respectively.APT values combined with DKI-derived parameters predicted LVSI better than when they were used separately,in which APT values combined with MK and MD values predicted LVSI of cervical cancer with the largest AUC,sensitivity of 91.7％,specificity of 80.0％,and Youden's index of 0.717.Conclusion Preoperative APT imaging and DKI have important value in predicting LVSI of cervical cancer,and the combined application of the two can improve the prediction efficacy,which has certain clinical application value.

[Objective]Based on the propensity score matching method to explore the therapeutic effect of lever positioning manipulation in the treatment of L4/5 different types of lumbar disc herniation.[Methods]A prospective cohort design was used to select 122 patients with L4/5 lumbar disc herniation and divide them into unilateral group,bilateral group and central group.Samples with balanced covariates were obtained after matching,including 36 patients in unilateral group,35 patients in bilateral group and 35 patients in central group.All patients in the three groups were treated with leverage positioning technique,and all patients in the three groups were treated 3 times a week,once every other day,for a total of 2 weeks.Pain Visual Analogue Scale(VAS)score and Japanese Orthopaedic Association(JOA)score were observed before and after treatment to evaluate the differences in the postoperative effects of the three groups.[Results]The covariates of age,sex,course of disease,VAS score and JOA score were all balanced after matching(P>0.05).The results of following-up after 2 weeks and 6 months of treatment showed that the VAS score and JOA score were statistically significant(P<0.05),the distant and near term curative effect of lever positioning manipulation in the treatment of unilateral lumbar disc herniation was better than bilateral and central disc herniation(P<0.05).[Conclusion]The clinical efficacy of unilateral lumbar disc herniation is superior to bilateral and central disc herniation in the treatment of the same segment of lumbar disc herniation with leverage positioning manipulation.

Macrophage extracellular traps(METs)are extracellular fibrous web-like structures produced by macrophages.METs play a crucial role in the development and progression of various cardiovascular diseases(CVDs),including atherosclerosis and myocardial infarction.This article summarizes the mechanism of METs in CVDs,future research directions and the possibility of using METs as potential therapeutic targets for clinical diseases.