[摘 要] 目的：探讨甲硫氨酸限制对肺腺癌（LUAD）细胞增殖、凋亡及磷酸戊糖途径的影响。方法：将H1299、A549细胞分为Met+组和Met−组，分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d，采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响，PI染色法检测细胞周期分布，Annexin Ⅴ-PE/7AAD标记细胞凋亡，利用DCFH-DA探针检测细胞内ROS水平，WST-8法和DTNB法分别测定细胞内NADPH与GSH含量；通过癌症基因组图谱（TCGA）数据库分析葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）表达与甲硫氨酸代谢通路的关系；采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸（SAM）对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果：甲硫氨酸限制显著抑制H1299和A549细胞增殖（均P < 0.01），将细胞周期阻滞于G2/M期（均P < 0.05），显著升高细胞内总ROS水平（均P < 0.001）并促进细胞凋亡（均P < 0.001）；同时，甲硫氨酸限制显著降低了细胞内NADPH和GSH水平（均P < 0.01），抑制DNA合成（均P < 0.01）。分析TCAG数据发现，G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关（均P < 0.001），甲硫氨酸限制下调G6PD和6PGD蛋白表达（均P < 0.01），而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制（均P < 0.01），提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论：甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖，为甲硫氨酸限制疗法治疗LUAD提供实验依据。

Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective To investigate the application effects of different myocardial protective solutions in total thoracoscopic minimally invasive aortic valve replacement surgery.Methods The clinical data of 72 patients with total thoracoscopic minimally invasive aortic valve replacement surgery in this hospital from May 2020 to January 2024 were analyzed retrospectively.The patients were divided into the St Thomas cardioplegia group(STH group,n=13),del Nido cardioplegia group(DN group,n=24),histidine tryptophan ketoglutar-ate solution group(HTK group,n=35)according to the different myocardial protective solutions.The levels of lactate(Lac)before and during surgery,the highest levels of myocardial creatine kinase isoenzyme(CK-MB),high-sensitivity troponin T(TnT)and creatinine(Cr)before operation,on the operative day and after surgery as well as the duration of extracorporeal circulation,aortic cross-clamping time,maximum flow rate,minimum bladder temperature,cardioplegia perfusion times,number of defibrillation after aortic de-clamping,postoperative ventilator assisted time,ICU stay duration and postoperative hospitalization duration were com-pared among the three groups.Results Except for 1 case of HTK was discharged automatically after surgery,the other 71 cases recovered and discharged according to the doctor's advice.There were no statistically signif-icant differences in the age,body weight,extracorporeal circulation time,aortic blocking time,maximum flow volume of extracorporeal circulation,minimum bladder temperature of extracorporeal circulation,Lac before extracorporeal circulation,highest Lac during extracorporeal circulation,assistant time of postoperative venti-lator,ICU stay duration,postoperative hospitalization duration,serum Cr before operation,Cr on operative day,preoperative TnT,postoperative TnT on operative day,postoperative highest TnT,preoperative CK-MB,postoperative CK-MB on operative day and postoperative highest CK-MB among the three groups(P＞0.05).There were statistically significant differences in the defibrillation ratio after aortic de-clamping and perfusion frequency of myocardial protective solution(P＜0.05).There was statistically significant difference in the perfusion frequency of myocardial protective solution in pairwise comparison among groups(P＜0.05),and the defibrillation ratio after aortic de-clamping had statistical difference between the DN group and HTK group(P＜0.05).Conclusion DN,STH and HTK all have good myocardial protective effect in total thoraco-scopic minimally invasive aortic valve surgery.HTK has the advantages of less perfusion times and decreasing the operative procedures compared with DN and STH;DN has the advantage of lower use for electrical defib-rillation correcting arrhythmias after aortic opening over HTK.

Objective To study the differences in features of event-related potentials(ERPs)and target detection accuracy between five brain regions(frontal,temporal,central,parietal,and occipital)in target detection tasks based on rapid serial visual presentation(RSVP)brain computer interface(BCI)under six target concealment conditions.Methods Twelve participants were selected for the study,whose scalp electroencephalogram(EEG)signals were collected under the six concealment conditions using a NeuroScan SynAmps2 EEG acquisition system.The ERP waveforms,P300 amplitudes and latencies,among other things,were compared across the five brain regions.The hierarchical discriminant component analysis(HDCA)algorithm was used to classify the EEG signals while the differences in classification accuracy were probed across the five brain regions.Results(1)Under the six concealment conditions,target images elicited distinct ERP waveforms in all the five brain regions;(2)For P300 amplitudes,the temporal region exhibited the smallest values;(3)Regarding P300 latencies,the parietal and central regions showed longer durations than other brain regions(except for small camouflage and small occlusion conditions);(4)In terms of classification accuracy,the parietal and central regions outperformed other brain regions(except for the large camouflage condition).Conclusion The selection of parietal and central channels can offer a new perspective for enhancing the performance in concealed target detection based on RSVP-BCI,and is expected to spark new ideas for the design of miniaturized,simple and wearable BCI devices.

Runt-related transcription factor(RUNX1)is a transcription factor closely involved in hematopoiesis.RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors,especially in acute myeloid leukemia.Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases.RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes.The expression of RUNX1 in mesenchymal stem cells,chondrocytes,and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones.RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts,which may be influenced by sexual dimorphism.In addition,RUNX1 deficiency contributes to the pathogenesis of osteoarthritis,delayed fracture healing,and osteoporosis,which was revealed by the RUNX1 conditional knockout modeling in mice.However,the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes,the sexual dimorphism of activities of osteoclasts,as well as bone loss in diabetes mellitus,senescence,infection,chronic inflammation,etc,are still not fully understood.This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology,offering new ideas for using RUNX1 as a potential target for bone related diseases,especially osteoarthritis,delayed fracture healing,and osteoporosis.

Objective:To analyze the application and funding status of various projects of nuclear medicine and molecular imaging supported by the National Natural Science Foundation of China (NSFC) from 2013 to 2022, and explore the challenges faced by basic research and clinical transformation in this field.Methods:From 2013 to 2022, application and funding information of nuclear medicine and molecular imaging projects (secondary code H2704, H2706) from five departments of Medical Science Department of NSFC were retrospectively collected. The number of applications, number of funding, funding direction, funding intensity, distribution of supporting units and research hotspots of various projects in this field were analyzed.Results:From 2013 to 2022, the total number of applications of various projects in the field of nuclear medicine and molecular imaging reached 5 387, and the total number of grants reached 899. The number of applications and grants showed a steady growth trend. The overall funding intensity increased from 48.935 0 million yuan in 2013 to 59.495 4 million yuan in 2022, with the increase of 21.58%. Among all supporting units, Shanghai Jiao Tong University topped the list for both the number of applications (440) and the number of grants (82), Xiamen University ranked the first in terms of overall funding rate (25.42%, 30/118), and Peking University ranked the first in terms of total funding intensity (41.897 1 million yuan). Research hotspots focused on the construction of tumor targeted molecular probes and precise imaging of tumor internal molecular components.Conclusion:In the past decade, the number of related projects and total funding of nuclear medicine and molecular imaging supported by NSFC have steadily increased, and the types of funded projects are diverse and interdisciplinary, promoting the innovative development of nuclear medicine and molecular imaging disciplines in China.

Objective:To evaluate the effect of 3D printed models assisted teaching method on clinical teaching of hip revision and improve the teaching quality.Methods:Fifty students who were in the standardized training for surgical specialty from Peking University Third Hospital were divided into a control group and an experimental group, with 25 students in each group. The control group was taught by traditional methods, while the experimental group was taught by 3D printed models. After the training, professional theory test and teaching evaluation questionnaire survey were conducted among the members of the two groups, and statistical analysis was made on the students' professional theory test scores, learning interests and teaching satisfaction. SPSS 18.0 was used for t test. Results:The theoretical scores of the experimental group [(84.60±5.76) points] were higher than those of the control group [(78.20±6.90) points], and the difference was statistically significant ( P<0.05). The teaching satisfaction and learning interest of the experimental group were both better than those of the control group [(4.72±0.46) vs. (4.28±0.61), (4.76±0.44) vs. (4.28±0.54)], with statistically significant differences ( P<0.05). Conclusion:The 3D printed model assisted teaching can effectively deepen students' understanding of hip joint structure, improve the teaching quality, and enhance their enthusiasm and initiative in learning.

Objective To visualize and analyze the literature related to immunotherapy for prostate cancer published in the past 20 years through bibliometric analysis, and to explore the research progress and cutting-edge trends in this field. Methods The Web of Science core collection database was searched for literature related to immunotherapy for prostate cancer published from 2002 to 2021. CiteSpace and VOSviewer software were used to visualize and analyze the data and map the evolution of hotspots. Results There were 2 326 papers were finally included after excluding irrelevant studies. The field of immunotherapy for prostate cancer is in a rapid development stage; the United States has a great influence and China has a significant latecomer advantage; the National Cancer Institute, Memorial Sloan-Kettering Cancer Center and University of California, San Francisco are the main research institutions; American authors Gulley JL, Schlom J and Japanese author Itoh K have the highest number of publications. Currently, the main research hotspot is immune checkpoint inhibitors, and high-quality clinical trials are continuing to drive this process forward. Conclusion The exploration of novel immune pathways and the combination of different therapies will be the main trend of future research in immunotherapy for prostate cancer.

Objective:To make Excel spreadsheet of arterial blood gas analysis to judge the types of acid-base imbalance quickly and accurately, and guide the clinical treatment of acid-base disorders.Methods:According to the Henderson-Hasselbalch equation, the compensation formula of acid-base imbalance prediction, the theory of acid-base balance and the related research progress, the analysis process of acid-base balance disorder was settled, and the IF function in Microsoft Office Excel 2003 was used to edit the formula to make Excel spreadsheet for arterial blood gas analysis.Once the pH value, artery blood carbon dioxide pressure (PaCO 2), actual bicarbonate (HCO 3-), sodiumion (Na + ), chlorineion (Cl -) and compensatory time-limited parameters were input, the types of acid-base imbalance can be shown.Arterial blood gas analysis of 185 cases from intensive care unit at Xuzhou Central Hospital was determined by Excel spreadsheet group and manual group respectively, the results and time of judging the type of acid-base imbalance were compared between two groups for statistical analysis. Results:The results of acid-base imbalance between two groups were compared, and 42 cases were normal and simple acid-base and the consistent rate was 100%, double acid-base imbalances of 107 cases with the consistent rate of 97.20%, triple acid-base imbalances of 36 cases with the consistent rate of 91.67%.After Kappa consistency test (Kappa value=0.944) and Pair chi-square Test (McNemar-Bowker Test)( P=0.223), the results of two groups were consistent.It took less time to judge the results of normal or simple acid-base imbalance[(32.32±4.26)s vs.(75.88±19.22)s], double acid-base imbalance[(31.28±5.31)s vs.(137.56±37.64)s] and triple acid-base imbalance[(32.98±4.23)s vs.(315.09±89.37)s] by the Excel spreadsheet group compared with the manual group, and the differences were statistically significant ( P<0.01). Conclusion:The automatic judging of Excel spreadsheet for arterial blood gas analysis can quickly and accurately determine the types of acid-base imbalance in arterial blood gas analysis and has more advantages for triple acid and base imbalance especially with simple interface and simple operation.And it can avoid the missing judgment of acid and base imbalance when pH is 7.35 to 7.45.