[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。

AIM: To compare the control effect of spherical and toric orthokeratology on low-to-moderate myopia with astigmatism(-1.00--1.50 DC)in adolescents.METHODS: The clinical data of 119 cases(119 eyes)of low-to-moderate myopia with astigmatism(-1.00--1.50 DC)adolescents who were treated and fitted with orthokeratology in the ophthalmology department of Sichuan Provincial People's Hospital from June 2021 to January 2022 were retrospectively analyzed. They were divided into spherical group, with 65 cases(65 eyes), and toric group, with 54 cases(54 eyes)according to the type of orthokeratology. The changes of uncorrected visual acuity(UCVA), axial length and corneal astigmatism before and after wearing lenses were recorded to evaluate the therapeutic effect.RESULTS: The UCVA of both the groups significantly improved at 1 and 2 a after wearing lenses(all P<0.01); corneal astigmatism decreased, but there was no significant difference(all P>0.05); the axial length was longer than that before wearing lenses(P<0.01). There were no statistical significant differences in the UCVA and corneal astigmatism between the spherical group and the toric group(Fintergroup=0.829,Pintergroup=0.364; Fintergroup=0.997,Pintergroup=0.320); and there were no statistical significant differences in the axial length growth between the spherical group and the toric group after wearing lenses for 1 a(0.18±0.11 mm vs 0.17±0.14 mm), and 2 a(0.17±0.10 mm vs 0.16±0.10 mm; all P>0.05).CONCLUSION: Both orthokeratology lenses can improve the UCVA, reduce corneal astigmatism, and delay axial length growth of adolescents with low-to-moderate myopia with astigmatism(-1.00--1.50 DC), and there are no significant differences in the control effect of spherical design orthokeratology and the toric design orthokeratology on myopia.

Objective To investigate the effect of growth differentiation factor 15(GDF15)on apoptosis and insulin secretion of MIN6 cells under high glucose conditions.Methods The mouse pancreatic islet β cell line(MIN6 cells)were divided into four groups:NG group,NG+rGDF15 group,HG group,and HG+rGDF15 group.The cell morphology among groups were observed,the apoptosis rate,the protein expression levels of Bcl-2 and Bax and the insulin level was detected.Results HG group exhibited significant cellular damage,characterized by upregulated apoptosis-promoting protein Bax and downregulated apoptosis-suppressing protein Bcl-2 expression,accompanied by a marked increase in apoptosis rate and a substantial decrease in insulin secretion(P＜0.01).Administration of recombinant GDF15 protein improved MIN6 cell morphology,significantly reduced Bax protein relative expression,elevated Bcl-2 protein relative expression,markedly decreased apoptosis rate,and enhanced insulin secretion(P＜0.01).Conclusion GDF15 can mitigate high glucose-induced MIN6 cell damage.

Objective:To investigate the subacute toxicity and target organs of triethylenediammonium perchlorate ammonium complex salt (DAP-4) .Methods:In August 2024, 40 SPF-grade SD rats were selected, with 10 rats in each group, half male and half female. There were 45, 140, and 420 mg/kg DAP-4 groups and a control group. Rats in each dose DAP-4 group were orally administered the corresponding amount of DAP-4 solution, while the control group was given the same dose of 1% sodium carboxymethyl cellulose. SD rats were given intragastric administration once a day for 28 consecutive days. The behaviors, histopathological changes, and blood physiological and biochemical indicators of rats were detected at the corresponding time points respectively. One-way analysis of variance was used for the comparison of quantitative data between groups.Results:Compared with the control group, the body weight, food intake and food utilization rate of female and male rats in the 420 mg/kg DAP-4 group were significantly decreased ( P<0.05), while no abnormalities were observed in the other dose groups. Compared with the control group, the white blood cell count of female rats in the 420 mg/kg DAP-4 group decreased, while the hemoglobin and hematocrit decreased and the total serum protein increased of male rats ( P<0.05). Compared with the control group, fibrinogen was increased in both female and male rats in the 420 mg/kg DAP-4 group, and the thrombin time of female rats was shortened ( P<0.05). In each dose group, the livers of female and male rats showed varying degrees of vacuolar degeneration, and the renal tubules of female rats were swollen. Conclusion:420 mg/kg DAP-4 can cause damage to the liver and kidney of rats, and the maximal no effect level of DAP-4 for rats is 140 mg/kg.

Objective:To compare and analyze the similarities and differences in clinical manifestations, laboratory findings, pathological characteristics, and prognosis between urticarial vasculitis (UV) and chronic spontaneous urticaria with pigmentation (CSUwp) .Methods:A retrospective analysis was conducted on the clinical data and follow-up results from 35 UV patients and 54 CSUwp patients who attended the Department of Dermatology, Southwest Hospital, Army Medical University from 2014 to 2024. The clinical characteristics (duration of rash, pigmentation, petechiae and ecchymosis, itching, burning sensation, fever, fatigue, skin lesion characteristics, etc.) , laboratory test results, pathological features, and prognosis were compared between the two groups. Statistical analysis was carried out by t test, chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis. Results:There were no significant differences in gender, age, or age of onset between the UV group and CSUwp group (all P < 0.05) . The proportions of patients with petechiae/purpura (68.57% [24/35] vs. 11.11% [6/54]) , and those with burning sensation (22.86% [8/35] vs. 3.70% [2/54]) were significantly higher in the UV group than in the CSUwp group (both P < 0.05) . Compared with the CSUwp patients, the UV patients presented with a greater number of lesions, larger lesion areas, and more frequent involvement of the lower limbs (all P < 0.05) , also showed significantly higher incidence rates of peripheral blood complement reduction, perivascular neutrophil infiltration, nuclear dust, fibrinoid necrosis of the vessel wall, and erythrocyte extravasation (all P < 0.05) , as well as more extensive dermal perivascular inflammation ( Z = -4.506, P < 0.001) . Among patients who achieved remission, the natural disease course was significantly longer in the CSUwp patients than in the UV patients (6.00 [2.5, 24] months vs. 2.00 [0.5, 24] months; Z = -2.618, P = 0.009]. However, the survival analysis showed no significant difference in the natural disease course or clinical outcomes between the two groups ( χ2 = 2.771, P = 0.096) . There were also no significant differences in rash duration or in the incidence rates of itching, angioedema, or joint pain between the two groups (all P > 0.05) . Conclusions:UV patients exhibited certain differences from CSUwp patients in clinical characteristics, laboratory test results, histopathological features, and prognosis. However, whether their natural disease courses differ requires further follow-up studies to confirm.

Guanylate binding protein subunit β-2(GNB2)is an important part of G protein family.In the process of cell signal transduction,GNB2 plays a structural support and regulatory role in G protein complex,ensuring the correct transmission and amplification of signals,interacting with receptors and regulating vari-ous effector enzymes and ion channels,and mediating a variety of physiological functions.Therefore,GNB2 plays a key role in cell signaling,and participates in the regulation of cell proliferation,differentiation and mi-gration and other biological processes.This article reviews the research progress of GNB2,focusing on its structure,function,regulatory mechanism,disease correlation and importance in tumor research.

Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective To apply a multidimensional neonatal nutritional risk screening scale for hospitalized premature infants to explore its predictive value for extrauterine growth restriction(EUGR)at the time of discharge.Methods A total of 104 premature infants hospitalized in the Neonatal Department of the Second Affiliated Hospital of Kunming Medical University from January 2023 to September 2023 were selected as research subjects.Nutritional risk screening was conducted within 24 hours of admission and weekly thereafter using the multidimensional neonatal nutritional risk screening scale.Scoring was based on four dimensions(birth status,weight changes,nutritional intake methods,and disease diagnosis),with a total score of ≥ 8 indicating high risk;≥4 and＜8 indicating moderate risk;and＜4 indicating low risk.EUGR at the time of discharge was the primary clinical outcome indicator.Receiver operating characteristic(ROC)curves were constructed to explore the predictive value of neonatal nutritional risk screening for EUGR in premature infants.Results At discharge,40 premature infants(38.5％)experienced EUGR.The nutritional risk screening scores of the EUGR group on day 7 of hospitalization were higher than those of the non-EUGR group(P＜0.05).The rate of high nutritional risk on day 7 of hospitalization was highest(7.9％in the non-EUGR group,22％in the EUGR group,and 13.5％overall).On both day 1 and day 7 of hospitalization,the rate of high nutritional risk in the EUGR group was higher than that in the non-EUGR group(P＜0.05).There were significant differences in the nutritional risk screening scores on day 7,birth weight Z-scores,discharge corrected gestational age weight Z-scores,and serum albumin levels between the EUGR and non-EUGR groups(P＜0.05).ROC curves were plotted,yielding AUCs of 0.625(95％CI 0.514,0.736),0.652(95％CI 0.544,0.760),0.674(95％CI 0.561,0.786),and 0.641(95％CI 0.531,0.750),indicating certain predictive value.A combined predictive ROC model yielded an AUC of 0.786(95％CI 0.692,0.880)for EUGR,which was higher than the AUCs for individual indicators(P＜0.001).Conclusion The occurrence of EUGR is relatively common among hospitalized premature infants.The nutritional risk is highest during the first week of hospitalization.The multidimensional neonatal nutritional risk screening scale can dynamically assess nutritional risk during hospitalization and may serve as one of the early warning indicators for EUGR in premature infants.The predictive efficacy for EUGR is enhanced when combined with birth weight Z-scores,discharge weight Z-scores,and serum albumin,providing a basis for individualized nutritional management of premature infants.

Objective To investigate the feasibility of a "pericardial lining" modified Bentall procedure for the treatment of patients with aortic root aneurysm. Methods This was a retrospective study that consecutively enrolled patients treated at the Affiliated Suzhou Hospital of Nanjing Medical University, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, and the First People's Hospital of Guangyuan from January 2023 to February 2024. Preoperative clinical data, imaging findings (including echocardiography and CT scans of the aortic root and the entire aorta), details of coronary artery management, surgical outcomes, and postoperative follow-up results were collected. All patients underwent the "pericardial lining" modified Bentall procedure: the aortic valve was replaced, and an autologous pericardial patch was divided into three equal leaflets based on the circumference of the aortic annulus measured by a valve sizer. These leaflets were then sutured to the aortic annulus. Fenestrations were created in two of the pericardial leaflets for anastomosis with the left and right coronary ostia. The pericardial leaflets were sutured to the wall of the aortic sinuses to form an integrated structure, thereby narrowing the sinus portion. A prosthetic vascular graft was anastomosed to the proximal and distal aorta, and no aortic root-to-right atrium shunt was created. Results A total of 5 patients, aged 37 to 68 years, were included. The preoperative Society of Thoracic Surgeons (STS) risk scores ranged from 2.8% to 3.9%. The diameter of the ascending aorta was 40-73 mm, the left ventricular end-diastolic diameter (LVEDD) was 45-71 mm, and the left ventricular ejection fraction (LVEF) was 47%-64%. Intraoperatively, the aortic cross-clamp time ranged from 85 to 180 min, and the cardiopulmonary bypass time ranged from 110 to 302 min. Postoperative follow-up echocardiography revealed that the ascending aortic diameter was 27-35 mm, LVEDD was 39-57 mm, and LVEF was 43%-61%. All surgeries were completed successfully with satisfactory immediate outcomes and no intraoperative complications. During the follow-up period, there was no mortality or reoperation. Conclusion For patients with aortic root aneurysm, the "pericardial lining" modified Bentall procedure yields satisfactory preliminary results, and the technique is demonstrated to be feasible.