Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective To investigate the MRI characteristics of subventricular zone(SVZ)-associated isocitrate dehydrogenase(IDH)wild-type glioblastoma(GBM)and their correlations with Ki-67 expression and O6-methylguanine-DNA methyltransferase(MGMT)promoter methylation status.Methods A retrospective analysis was conducted on data of 78 patients with IDH wild-type GBM who underwent surgery and received pathological confirmation.Preoperative MRI contrast-enhanced T1 WI sequences were used to assess SVZ involvement,and postoperative molecular testing of tumor markers,including Ki-67 expression and MGMT methylation status,was utilized to categorize the patients accordingly.Results The SVZ involved(+)group(P＜0.001)and the MGMT(+)group(P=0.036)exhibited significantly larger tumor volumes.There were no significant differences between the groups in terms of gender,age,left/right hemispheric lateralization,or specific brain lobe distribution.There was no significant association between Ki-67 expression levels,MGMT methylation status,and SVZ involvement,respectively.Conclusion The SVZ(+)group and the MGMT(+)group demonstrates a wider range of tumor invasion.

The limitations of endovascular repair technology for organ arterial injury at the present stage were analyzed,and an endovascular repair device for organ arterial trunk injury was designed to make up for the shortcomings of the existing technology and improve the success rate of treatment.The new balloon injection device is mainly used for the repair of organ arterial trunk injury,which has good passing ability,can effective repair wound and hemostasis,and protect organ function.In clinical practice,it provided a new treatment method for visceral artery trunk injury with limited use of conventional endovascular treatment techniques and no open surgery opportunity.This device can effectively solve the problems of organ dysfunction caused by arterial embolization in the case of arterial trunk injury,and limited by the degree of tube tortuous in the case of stent isolation surgery.

Objective:To evaluate the feasibility of artificial intelligence (AI) diagnosis of pulmonary nodules on virtual non-contrast(VNC) images derived from dual-layer detector spectral CT.Methods:Totally 52 patients who underwent non-contrast and dual-phase enhanced chest CT scan from May 2022 to November 2022 were enrolled in this study. The VNC images of lung were reconstructed based on venous phase data. CT values and image noise of lung parenchyma, signal-to-noise ratio (SNR) were measured. The dose-length product (DLP) of each scan was recorded and the effective dose ( E) was calculated. All of the objective indicators of image quality and radiation dose were compared by Paired t test. Image quality was evaluated subjectively by two radiologists and compared with Wilcoxon non-parametric test. Wilcoxon symbolic rank test was used to compare the sensitivity and false positive detection rate (FPDR) of AI diagnosis between two groups. Results:Compared with TNC, the noise of venous VNC image was decreased by 13.8%, SNR increased by 14.9%, and both of DLP and E decreased by 33.3% ( t=5.82, -5.35, 22.93, 22.92, P <0.05). There were no significant differences in CT values and subjective scores between 2 groups ( P >0.05). For different types of pulmonary nodules, there was no statistical difference in the sensitivity of AI diagnosis between two groups ( P >0.05). For solid nodules with diameter ≤4 mm and all pulmonary nodules in general, FPDR in VNC group was slightly increased with statistical significance ( Z=-2.03, -3.09, P<0.05), while for other types of pulmonary nodules, there was no statistical difference ( P >0.05). Conclusions:The VNC images of thoracic venous phase based on spectral CT can significantly reduce the radiation dose of patients while the image quality and the AI diagnostic sensitivity of pulmonary nodules remain unchanged, and the FPDR without significantly increase. And it could replace TNC for daily routine.

Humans ; Benzodiazepines ; Hypnotics and Sedatives/therapeutic use* ; Intensive Care Units ; Midazolam

Objective:To investigate the effect of SCN1A gene polymorphism (SCN1A-rs3812718) on the alterations of spontaneous brain activity using amplitude of low-frequency fluctuations (ALFF) of MR in patients with temporal lobe epilepsy (TLE).Methods:A total of 37 TLE patients (TLE group) admitted to the Epilepsy Center of the 900th Hospital of Joint Logistic Team from March 2018 to August 2019 were retrospectively analyzed, and another 28 healthy volunteers matched for gender, age, and years of education with the TLE group were selected as the healthy control group (HC group). Sixty-five subjects were divided into four groups by genotype and diagnosis: 34 cases in AA/AG-TLE subgroup, 3 cases in GG-TLE subgroup, 20 cases in AA/AG-HC subgroup and 8 cases in GG-HC subgroup. All subjects underwent sagittal 3D-T 1WI and resting-state functional MRI using a Siemens 3.0 T Trio Tim MR scanner. Then ALFF values of the four groups were calculated using DPABI by the MATLAB 2010 platform. The ALFF values between two groups were compared by independent samples t-test. The ALFF values of different genotypes at rs3812718 locus in TLE and HC group were analyzed by multivariate analysis of variance to find out the corresponding brain regions with interaction, and then post hoc simple effect analysis was performed. Results:The ALFF values in TLE group significantly increased in left marginal lobe, left parahippocampal gyrus, left fusiform gyrus, left hippocampus, right insular lobe and right inferior temporal gyrus (Alphasim corrected P<0.001) and decreased in the left superior frontal gyrus, left middle frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right precuneus, left precuneus, bilateral cingulate gyrus and right angular gyrus (Alphasim correction P<0.05) compared with HC group. Subjects carrying the non-risk G allele had higher ALFF values in the right inferior temporal gyrus, right fusiform gyrus, and right cerebellum than subjects carrying the risk A allele ( t=3.30, Alphasim corrected P=0.002). There was a significant interaction effect on posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus, left superior parietal lobule and right precuneus of TLE patients with SCN1A-rs3812718 genotype. Post-hoc simple effect analysis showed that ALFF significantly increased in the left posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus and left fusiform gyrus in GG-TLE subgroup ( t=5.97, P<0.001), but significantly decreased in the right superior parietal lobule, right precuneus, right posterior cerebellar lobe in AA/AG-TLE subgroup compared to the HC group. Compared with GG-TLE subgroup, ALFF in left posterior cerebellar lobe, left fusiform gyrus and left inferior temporal gyrus decreased in AA/AG-TLE subgroup. Conclusion:SCN1A gene polymorphism in the rs3812718 locus affects spontaneous neural activity in resting state, which may be one of the pathophysiological mechanisms of TLE.

Objective:To investigate the relationship between absolute lymphocyte count (ALC) and prognosis of extranodal nasal NK/T cell lymphoma (ENKTL).Methods:The data of 184 patients with ENKTL who were admitted to Shanxi Provincial Cancer Hospital and the Second People's Hospital of Datong in Shanxi Province from January 2002 to December 2018 were retrospectively analyzed. Contal-O'Quigley variable point method was used to calculate the optimal cut-off value of ALC for predicting the prognosis of ENKTL, and the patients were divided into two groups based on this value. Kaplan-Meier method was used to analyze the survival of the two groups of patients. Cox proportional hazard regression model was used for univariate and multivariate survival analyses.Results:According to the Contal-O'Quigley variable point method, the best cut-off value of ALC for predicting ENKTL prognosis was 1.5×10 9/L. According to this value, patients were divided into ALC>1.5×10 9/L group (98 cases) and ALC≤1.5×10 9/L group (86 cases). Compared with the ALC≤1.5×10 9/L group, the proportions of patients with Eastern Cooperative Oncology Group (ECOG) score ≥2 points, serum lactate dehydrogenase (LDH)> 245 U/L, Korean prognostic index (KPI) score 2-4 points and international prognostic index (IPI) score 2-5 points were lower in the ALC>1.5×10 9/L group, but the proportion of patients with hemoglobin > 120 g/L was higher (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in the ALC>1.5×10 9/L group were better than those in the ALC≤1.5×10 9/L group (3-year OS rate: 65.7% vs. 45.4%, 5-year OS rate: 61.0% vs. 36.6%; 3-year PFS rate: 61.7% vs. 41.0%, 5-year PFS rate: 51.9% vs. 32.2%; all P < 0.05). Multivariate Cox regression analysis showed that ECOG score, serum LDH level, ALC, radiotherapy and L-asparaginase-containing chemotherapy were independent influencing factors of OS and PFS (all P < 0.05), and for OS, when ALC>1.5×10 9/L compared with≤1.5×10 9/L, RR was 0.634 (95% CI 0.398-1.008, P=0.050), and for PFS, RR was 0.625 (95% CI 0.406-0.962, P=0.033). Conclusion:Patients with high ALC have good prognosis, and therefore ALC may be a powerful prognostic factor of ENKTL.

Objective: To analyze the function of essential hypertension′s working memory network by using task-fMRI and independent component analysis (ICA). Methods: According to the enrollment criteria, 24 hypertensive patients and 23 healthy controls (May 2016 to January 2017) in the 900 Hospital of the Joint Service Support Force were collected, who underwent task-state functional MRI data acquisition of N-back by using Siemens 3.0 T MRI. All subjects completed neuropsychological cognitive tests, blood pressure measurements and biochemical tests before MRI. Task-state functional MRI was analyzed by SPM 12, and independent component analysis was performed by GIFT 4.0 software. The independent-samples t-test was used to analyze the maps of the two groups′s task-state fMRI and ICA. The results were adjusted by multiple comparison correction of Alphasim, P<0.05 showed that the difference was statistically significant. Results: Compared with the healthy group, the activation of left superior frontal gyrus and left middle frontal gyrus in hypertension group was enhanced (P<0.05), but there was no obvious weakened activation area. In the independent component analysis, the functional connectivity of left middle frontal gyrus and left anterior central gyrus in hypertension group was significantly lower than that in healthy control group (P<0.05), and there was no significant enhancement of functional connectivity. Conclusions The working memory network of patients with essential hypertension may change abnormally due to the influence of long-term hypertension. This kind of damage can compensate through the functional enhancement of brain regions, thus maintaining the normal cognitive level of hypertensive patients.

Objective: To observe the effects of electroacupuncture (EA) on depressive-like behavior, synaptic plasticity and 5-HTT protein expression of hippocampal CA1 region in the WKY model rats. Methods In this experiment, 10 male Wistar rats were selected as the normal group (Control), and 30 male WKY rats were randomly divided into model group, electroacupuncture group (EA) and sham needle group (Sham EA) . Behavioral testing was performed by the Sour Water Preference Experiment (SPT), the Open Field Experiment (OFT), and the Forced Swimming Experiment (FST) . The electrophysiological field potential experiment was used to detect the effect of electroacupuncture on LTP in the hippocampal CA1 region of rats with depression, which is the effect on synaptic plasticity. The expression of 5-HTT protein in hippocampal CA1 region was detected by Western blot. Results In the SPT, compared to the Control group, the sucrose solution intake was significantly reduced in the Model group (P ＜ 0.01) . It was improved after EA treatment compared to Sham EA group (P ＜ 0.05) . In the OFT, compared with the Control group, the center time, total move time, center distance, total distance, rearing and grooming incidents were all decreased in the Model group. Compared with the Model group, the center time and total move time in the EA group increased significantly after 3 weeks of treatment (P ＜0.05) . In the FST, duration of immobility was significantly (P ＜ 0.05) longer in the Model group comparing with the Control group. Compared with Sham EA group and Model group, the immobile time of EA group was significantly shorter (P ＜ 0.05) . Compared with the Control group, the fEPSP slope of the Model group was significantly shorter (P ＜ 0.001) .Compared with the Sham EA group, the fEPSP slope of the EA group increased significantly (P ＜ 0.001) . And the LTP of Sham EA and Model groups induced failure in hippocampal CA1 region, the LTP induction was successful after EA treatment. Compared with the Control group, the expression of 5-HTT protein was significantly increased (P＜0.001) .Compared with Sham EA group, the expression of 5-HTT protein in EA group decreased (P ＜ 0.001) . Conclusion EA could alleviate depression-like behaviors in depression model rats and reverse the impairment of hippocampus synaptic plasticity by decrease the over-expression of 5-HTT protein in hippocampal CA1 region. It may be one of the mechanisms of EA on depression.

Objective: To investigate the predictive value of CT evaluation of fatty liver for the severity of acute pancreatitis(AP). Methods: The clinical and imaging data of 325 patients with AP from January 2013 to December 2017 were retrospectively analyzed. The demographic characteristics, etiological types, AP severity classification, persistent organ failure and death were collected. According to the ratio of the CT value of the liver and spleen (CT valueratio), whether the patients had fatty liver and the severity of fatty liver were determined. The incidence of persistent organ failure and mortality in AP patients with or without fatty liver and between the different severity grades of fatty liver were compared. Univariate and multivariate Logistic regression analysis was used to assess the independent risk factors for persistent organ failure in AP. Results: Among the 325 AP patients, 86 (26.5%) patients were in line with the CT diagnostic criteria for fatty liver and 239 (73.5%) patients did not meet the CT diagnostic criteria of fatty liver. The incidence of persistent organ failure in AP patients with fatty liver (CT valueratio<1.0) was significantly higher than that without fatty liver (CT valueratio=1.0):17.4%(15/86) vs. 7.5%(18/239), P<0.05. The rate of persistent organ failure in AP patients increased proportionally with the severity grades of fatty liver [7.5% in patients without fatty liver, 7.5%(18/239) in mild (0.7P<0.05. Single factor analysis showed that sex, body mass index (BMI, ≥ 25 kg/m²), etiological type, combined fatty liver were associated with persistent organ failure in AP (P<0.05 or<0.01). Multiple factor Logistic regression analysis showed that the elderly (≥60 years old), high BMI (≥ 25 kg/m²) and combined fatty liver were independent risk factors for persistent organ failure in AP (P<0.05 or<0.01). Conclusions Assessment of fatty liver and its severity in AP patients by CT is valuable to predict the risk of persistent organ failure.