[摘 要] 目的：探讨miR-433对结直肠癌（CRC）细胞干细胞特性及5-氟尿嘧啶（5-FU）耐药性的影响，并阐明其潜在的分子调控机制。方法： 建立5-FU耐药的HCT-116细胞株。采用RT-qPCR和WB法检测miR-433及干细胞特性标志物（SOX2、OCT4、Nanog）的表达。通过双萤光素酶报告基因实验、免疫荧光和核质分离实验验证miR-433与靶基因YAP1的关系及YAP1对其亚细胞定位的影响。通过拯救实验确认miR-433/YAP1轴的功能。利用CCK-8法检测细胞对5-FU的敏感性。结果： 与亲代HCT-116/P细胞相比，耐药的HCT-116细胞株中miR-433表达显著下调（P < 0.05），而干细胞特性标志物（SOX2、OCT4、Nanog）表达上调（P < 0.05）。过表达miR-433能够抑制干细胞标志物的表达，并直接靶向YAP1，阻碍其核定位（P < 0.05）。恢复YAP1的表达能够部分逆转miR-433对干细胞标志物的抑制作用（P < 0.05）。功能上，上调miR-433显著增强了CRC细胞对5-FU的敏感性，而此效应同样可被YAP1的重新表达所削弱（P < 0.05）。结论： miR-433通过直接靶向YAP1通路，抑制CRC细胞的干细胞特性相关分子表型，并增强其对化疗药物的敏感性。miR-433/YAP1轴可能成为克服CRC 5-FU耐药的潜在新靶点。

Objective To explore the performance of gallium nitride(GaN)-based digital circuit chips applied in nuclear radiation environments and investigate the feasibility of their use in control chips for robots transporting injured personnel.Methods First,a GaN-based NAND gate digital circuit chip was fabricated.Second,both the GaN-based digital chip and the SN74AHCT1G00 silicon-based digital chip were irradiated with 60Co gamma-ray.The irradiation doses for the GaN-based digital chip were 1 Mrad(Si)and 2 Mrad(Si),while the irradiation dose for the SN74AHCT1G00 silicon-based digital chip was 1 Mrad(Si).Finally,the post-irradiation electrical performance of the two chips was measured using a Keithley 4200A-SCS semiconductor characterization system.Results Under 60Co gamma-ray irradiation doses of 1 Mrad(Si)and 2 Mrad(Si),the response delay of the GaN-based digital circuit chip was only on the order of 0.1 μs.In contrast,the response rate of the SN74AHCT1G00 silicon-based digital circuit chip significantly degraded under 60Co gamma-ray irradiation dose of 1 Mrad(Si),rendering it unable to perform the NAND gate logic function.Conclusion GaN-based digital circuit chips exhibit high radiation resistance in 60Co gamma-ray irradiation environments,with no significant performance degradation.Compared with silicon-based digital circuit chips,they demonstrate considerable advantages and can preliminarily meet the requirements for control chips of robots transporting injured personnel in nuclear radiation environments.

Objective To investigate the role and clinical significance of Calpain activity and 145 kDa cleavage fragments of αⅡ-spec-trin breakdown products(SBDP145)in systemic lupus erythematosus(SLE).Methods 124 patients with confirmed SLE and de-tailed clinical data were collected as the SLE group,and 75 healthy individuals who underwent physical examination during the same period were selected as the control group.Their serum samples were collected,and serum SBDP145 levels and Calpain activity were de-tected by the enzyme-linked immunosorbent assay(ELISA)and substrate-based method,respectively.The Mann-Whitney U test,Spearman rank correlation,univariate and multivariate Logistic regression,and receiver operating characteristic(ROC)curve were used to evaluate the clinical value of Calpain activity and SBDP145 in the diagnosis and assessment of SLE.Results Compared with healthy controls,serum Calpain activity([17.000[8.5000,33.500]RFU vs 7.500[4.000,12.500]RFU)and SBDP145 levels(5.283[3.532,9.463]ng/mL vs 1.472[0.994,2.212]ng/mL)in SLE patients were significantly increased(Z=-9.229,P<0.001;Z=-6.881,P<0.001).Furthermore,the Calpain activity was significantly correlated with SLE disease activity index(SLEDAI-2K)score(r=0.349,P<0.001).Logistic regression analysis showed that the increased Calpain activity and SBDP145 levels were significantly associated with the occurrence of SLE(OR=1.164,95％CI:1.016-1.334,P=0.029;OR=3.822,95％CI:1.928-7.574,P<0.001).The ROC curve analysis showed that the area under the ROC curve(AUCROC)of serum Calpain activity in distin-guishing SLE and healthy controls was 0.762(95％CI:0.697-0.827).When the cut-off value was 13.75 RFU,its sensitivity and speci-ficity were 63.1％and 81.1％,respectively.The AUCROC of serum SBDP145 levels in distinguishing SLE and healthy controls was 0.891(95％CI:0.845-0.936).When the cut-off value was 2.377 ng/mL,its sensitivity and specificity were 88.7％and 80.0％,re-spectively.The AUCROC,sensitivity,and specificity of combining the two with traditional SLE clinical indicators,including complement C3,erythrocyte sedimentation rate,and anti-dsDNA antibodies,in the diagnosis of SLE reached 0.986(95％CI:0.972-1.000),93.3％,and 96.0％,respectively.The Spearman correlation analysis results showed that the organ damage index(SDI)score of SLE patients was positively correlated with serum Calpain activity and SBDP145 levels(r=0.342,P<0.001;r=0.250,P=0.005).Con-clusion The elevated Calpain activity and SBDP145 levels are closely related to the occurrence and development of SLE,suggesting that they may be served as potential biomarkers for the diagnosis and assessment of SLE patients.

Objective To investigate the coagulation abnormalities and molecular genetic characteristics of a family with asymptomatic inherited fibrinogen disorders(IFD).Methods The clinical data of a family with IFD,including 5 individuals from two generations,were collected.Their peripheral blood coagulation indicators were detected.The coding sequences of FGA,FGB and FGG genes were amplified by PCR and Sanger sequencing was used to identify the candidate variants,which were further validated in the family mem-bers.The bioinformatic software was used to analyze the pathogenicity and conservation of the missense mutation and its effect on the spatial structure and function of the protein.Results The IFD patients had significantly low fibrinogen antigen(Fg:Ag)concentration and fibrinogen coagulation(Fg:C)activity concentration as well as prolonged thrombin time(TT),while coagulation indicators of the unaffected relatives were normal.The results of Sanger sequencing showed that all IFD patients carried a heterozygous missense variant of c.1001A>C(p.Asn334Thr)in the FGG gene.The bioinformatic analysis suggested that Asn334Thr was a pathogenic variant,while homology analysis indicated that the Asn334 locus was highly conserved in evolution.The analysis of protein spatial structure showed that the Asn334Thr mutation altered hydrogen bonds between amino acids.Conclusion The heterozygous missense variant c.1001A>C(p.Asn334Thr)in the FGG gene may be the pathogenic cause of the proband.The finding enriches the spectrum of FGG gene mutations and provides experimental evidence for the genetic counseling of affected families.

Objective To explore the performance of gallium nitride(GaN)-based digital circuit chips applied in nuclear radiation environments and investigate the feasibility of their use in control chips for robots transporting injured personnel.Methods First,a GaN-based NAND gate digital circuit chip was fabricated.Second,both the GaN-based digital chip and the SN74AHCT1G00 silicon-based digital chip were irradiated with 60Co gamma-ray.The irradiation doses for the GaN-based digital chip were 1 Mrad(Si)and 2 Mrad(Si),while the irradiation dose for the SN74AHCT1G00 silicon-based digital chip was 1 Mrad(Si).Finally,the post-irradiation electrical performance of the two chips was measured using a Keithley 4200A-SCS semiconductor characterization system.Results Under 60Co gamma-ray irradiation doses of 1 Mrad(Si)and 2 Mrad(Si),the response delay of the GaN-based digital circuit chip was only on the order of 0.1 μs.In contrast,the response rate of the SN74AHCT1G00 silicon-based digital circuit chip significantly degraded under 60Co gamma-ray irradiation dose of 1 Mrad(Si),rendering it unable to perform the NAND gate logic function.Conclusion GaN-based digital circuit chips exhibit high radiation resistance in 60Co gamma-ray irradiation environments,with no significant performance degradation.Compared with silicon-based digital circuit chips,they demonstrate considerable advantages and can preliminarily meet the requirements for control chips of robots transporting injured personnel in nuclear radiation environments.

Objective:To prepare nanoscale docetaxel-loaded lipid microbubbles(DLLM),characterize their physical and chemical properties,evaluate their biosafety and anti-tumor effects in vitro,and explore their potential as a targeted delivery system for chemotherapeutic drugs.Methods:DLLM was prepared by thin film hydration method.The morphology,particle size and distribution were characterized by transmission electron microscopy,scanning electron microscopy and particle size analyzer.The drug encapsulation efficiency was determined by high performance liquid chromatography.Human hepatoma HepG2 cells were used as a model to set up the control group(Control group),the docetaxel group(DOC group),the docetaxel-loaded lipid microbubbles group(DLLM group)and the docetaxel-loaded lipid microbubbles+ultrasound group(DLLM+US group).The cell morphology was observed by optical microscope,the cell survival rate was detected by CCK-8 method,and the apoptosis was detected by flow cytometry.The biocompatibility of microbubbles and their mediated ultrasound-enhanced anti-tumor effect were evaluated.Results:The prepared DLLM was regular spherical,with a particle size distribution range of 200-600 nm,an average particle size of 380 nm,and an encapsulation efficiency of 80.3％±2.6％.The cell viability of the DOC group and the DLLM+US group was significantly lower than that of the Control group(P＜0.01),and the apoptosis rate was significantly increased(P＜0.01).The cell viability of the DLLM+US group was lower than that of the DOC group(P＜0.05),and the apoptosis rate was higher than that of the DOC group(P＜0.05).There was no significant difference in cell viability and apoptosis rate between the DLLM group and the Control group(P＞0.05).Conclusions:The nano-scale DLLM prepared in this experiment has uniform particle size,high encapsulation efficiency,good stability and biocompatibility.DLLM can enhance the killing and pro-apoptotic effects of docetaxel on HepG2 cells under ultrasound irradiation.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Objective:To establish a normal data model of fetal right ventricular size and function using echocardiography，and to explore the clinical value of quantitative assessment of right ventricular size and function in the diagnosis of congenital heart diseases.Methods:（1）A simple random sampling method was employed to collect 1 004 pregnant women with normal singleton pregnancies at 24 to 32 +6 weeks of gestation who underwent fetal cardiac ultrasound examinations at the First Affiliated Hospital of Air Force Medical University from January 2021 to December 2023. Two-dimensional and M-mode echocardiography were used to measure the right ventricular end-diastolic diameter（RVEDD），right ventricular end-diastolic area（RVEDA），tricuspid annular plane systolic excursion（TAPSE）during systole，and the right ventricular fractional area change（RVFAC）was calculated. The correlations between the above parameters and ultrasound gestational age（USGA）were analyzed. Moreover，percentile growth curves for each parameter were plotted. With the above parameters as dependent variables and the USGA as the independent variable，a Z-score model was established through regression analysis.（2）A stratified sampling method was adopted to select 30 fetuses diagnosed with hypoplastic right heart syndrome（HRHS）and 30 fetuses diagnosed with pulmonary stenosis（PS）during the same period as the case group. The model was verified，and the morphological and functional characteristics of the right ventricle were analyzed. Results:The data of RVEDD，RVEDA，TAPSE，and RVFAC in normal fetuses showed a skewed distribution. Each parameter showed good linear correlations with USGA（ r=0.836，0.834，0.846，0.242；all P<0.001）. The constructed percentile curves for each parameter indicated that RVEDD，RVEDA and TAPSE increased significantly with the growth of USGA，while RVFAC showed a slow downward trend. All parameters in the HRHS group and TAPSE and RVFAC in the PS group deviated significantly from the normal reference range（all P<0.001）. Conclusions:By analyzing RVEDD，RVEDA，TAPSE and RVFAC of normal fetuses，the percentile and Z-score normal reference value models of multiple parameters of fetal right ventricular size and function have been established，providing corresponding standards for quantitative analysis.