Objective:To investigate the effect of lycopene on blood-brain barrier and nerve damage in rats with cerebral small vessel disease(CSVD)by regulating Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/vascular endo-thelial growth factor(VEGF)signaling pathway.Methods:Fifty CSVD rat models were prepared by in vitro injection of the same germ-line microemboli,and were randomly grouped into model group,low-dose lycopene(65 mg/kg)group,high-dose lycopene(85 mg/kg)group,AG490(JAK2 inhibitor,3.5 mg/kg)group,and high-dose lycopene(85 mg/kg)+AG490(3.5 mg/kg)group,with 10 cases in each group,another 10 SD rats were regarded as sham operation group.After grouping with lycopene and AG490,cognitive ability of rats was detected by Morris water maze test and dark avoidance test;permeability of blood-brain barrier in rats was detected by Evans blue method;the number of rat hippocampal neurons was detected by Nissl staining;levels of inflammatory factors prostaglandin E2(PGE2),tumor necrosis factor-α(TNF-α),and oxidative stress factors catalase(CAT),superoxide dismutase(SOD),malondialde-hyde(MDA)in rats brain tissue were detected by kits;expressions of matrix metalloproteinase(MMP)2,MMP9,tight junction-related proteins(ZO-1,Occludin)and JAK2/STAT3/VEGF pathway-related proteins in rats brain were detected by Western blotting.Results:Compared with sham operation group,the times of rats crossing the platform,the time of staying in the target quadrant,step through latency,the number of hippocampal neurons,levels of CAT and SOD in brain tissue,protein expressions of ZO-1,Occludin and VEGF,and p-JAK2/JAK2,p-STAT3/STAT3 were obviously decreased in model group(P<0.05),while the error times,Evans blue content,levels of brain tissue PGE2,TNF-α and MDA,and protein expressions of MMP2 and MMP9 were obviously increased(P<0.05).Compared with model group,the times of rats crossing the platform,the time of staying in the target quadrant,step through la-tency,the number of hippocampal neurons,levels of CAT and SOD in brain tissue,protein expressions of ZO-1,Occludin and VEGF,and p-JAK2/JAK2,p-STAT3/STAT3 were all increased in low-dose lycopene group and high-dose lycopene group(P<0.05),while the error times,Evans blue content,levels of brain tissue PGE2,TNF-α and MDA,and protein expressions of MMP2 and MMP9 were all decreased(P<0.05),and high dose lycopene was more effective;the change trend of each index in AG490 group was opposite to that in lycopene groups,and AG490 could reverse the effect of lycopene.Conclusion:Lycopene can inhibit inflammation and oxidative stress in CSVD rats by activating JAK2/STAT3/VEGF signaling pathway,thereby reducing the blood-brain barrier and nerve damage,and improving their cognitive ability.

Intraspinal metastasis from malignant carcinomas in other body parts is rarely repor-ted.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extr-amedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlap-ping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thy-mic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and ir-regular shape.

Objective To investigate the correlation between the expression of cysteine protease inhibitor S(CST4)and vascular endothelial growth factor-A(VEGF-A)in esophageal squamous cell carcinoma(ESCC)and clinical pathological parameters.Methods Immunohistochemistry was used to detect the expression of CST4 and VEGF-A in the tissues of 50 patients with ESCC,and the correla-tion between them and pathological parameters was analyzed.The enrichment and correlation of them were confirmed by combining the re-sults of Enrichr and GEO databases.Results Compared with adjacent tissues,the positive expression rates of CST4 and VEGF-A in ESCC was significantly increased(P＜0.05).There were significant differences in the positive expression rate of CST4 in ESCC with dif-ferent lymph node metastasis,depth of invasion,and neurovascular invasion(P＜0.05).There were significant differences in the positive expression rate of VEGF-A in ESCC with different lymph node metastasis,depth of invasion,neurovascular invasion,and pathological stage(P＜0.05).Kaplan-Meier survival analysis indicated that postoperative survival rate of patients was related to the expression of CST4 and VEGF-A,depth of invasion,TNM stage and lymph node metastasis(P＜0.05).Spearman correlation analysis showed a pos-itive correlation between the expression of CST4 and VEGF-A in ESCC tissues(r=0.601,P＜0.05).COX regression analysis showed that VEGF-A expression level,CST4 expression level,lymph node metastasis,depth of invasion and pathological stage were risk factors for survival(P＜0.05).Enrichment analysis showed that CST4 and VEGF-A play a synergistic role in cell migration and invasion.Conclusion CST4 and VEGF-A are higher expressed in ESCC tissues than normal tissues.They are involved in the development and metastasis of ESCC,and they are expected to be important indicators for the treatment and prognosis of ESCC.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Objective To investigate the prognostic value of preoperative serum albumin-to-globulin ratio (AGR) and neutrophil-lymphocyte ratio (NLR) in the overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC), and to establish an individualized nomogram model and evaluate its efficacy, in order to provide a possible evaluation basis for the clinical treatment and postoperative follow-up of ESCC patients. Methods AGR, NLR, clinicopathological and follow-up data of ESCC patients diagnosed via pathology in the Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University from 2010 to 2017 were collected. The correlation between NLR/AGR and clinicopathological data were analyzed. Kaplan-Meier analysis and log-rank test were used for survival analysis. The optimal cut-off values of AGR and NLR were determined by X-tile software, and the patients were accordingly divided into a high-level group and a low-level group. At the same time, univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting OS in the ESCC patients, and a nomogram prediction model was constructed and internally verified. The diagnostic efficacy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was evaluated by decision curve analysis. Results A total of 150 patients were included in this study, including 105 males and 45 females with a mean age of 62.3±9.3 years, and the follow-up time was 1-5 years. The 5-year OS rate of patients in the high-level AGR group was significantly higher than that in the low-level group (χ2=6.339, P=0.012), and the median OS of the two groups was 25 months and 12.5 months, respectively. The 5-year OS rate of patients in the high-level NLR group was significantly lower than that in the low-level NLR group (χ2=5.603, P=0.018), and the median OS of the two groups was 18 months and 39 months, respectively. Multivariate Cox analysis showed that AGR, NLR, T stage, lymph node metastasis, N stage, and differentiation were independent risk factors for the OS of ESCC patients. The C-index of the nomogram model was 0.689 [95%CI (0.640, 0.740)] after internal validation. The area under the ROC curve of predicting 1-, 3-, and 5-year OS rate was 0.773, 0.724 and 0.725, respectively. At the same time, the calibration curve and the decision curve suggest that the model had certain efficacy in predicting survival and prognosis. Conclusion Preoperative AGR and NLR are independent risk factors for ESCC patients. High level of AGR and low level of NLR may be associated with longer OS in the patients; the nomogram model based on AGR, NLR and clinicopathological features may be used as a method to predict the survival and prognosis of ESCC patients, which is expected to provide a reference for the development of personalized treatment for patients.

Objective To investigate the correlation between the expression of cysteine protease inhibitor S(CST4)and vascular endothelial growth factor-A(VEGF-A)in esophageal squamous cell carcinoma(ESCC)and clinical pathological parameters.Methods Immunohistochemistry was used to detect the expression of CST4 and VEGF-A in the tissues of 50 patients with ESCC,and the correla-tion between them and pathological parameters was analyzed.The enrichment and correlation of them were confirmed by combining the re-sults of Enrichr and GEO databases.Results Compared with adjacent tissues,the positive expression rates of CST4 and VEGF-A in ESCC was significantly increased(P＜0.05).There were significant differences in the positive expression rate of CST4 in ESCC with dif-ferent lymph node metastasis,depth of invasion,and neurovascular invasion(P＜0.05).There were significant differences in the positive expression rate of VEGF-A in ESCC with different lymph node metastasis,depth of invasion,neurovascular invasion,and pathological stage(P＜0.05).Kaplan-Meier survival analysis indicated that postoperative survival rate of patients was related to the expression of CST4 and VEGF-A,depth of invasion,TNM stage and lymph node metastasis(P＜0.05).Spearman correlation analysis showed a pos-itive correlation between the expression of CST4 and VEGF-A in ESCC tissues(r=0.601,P＜0.05).COX regression analysis showed that VEGF-A expression level,CST4 expression level,lymph node metastasis,depth of invasion and pathological stage were risk factors for survival(P＜0.05).Enrichment analysis showed that CST4 and VEGF-A play a synergistic role in cell migration and invasion.Conclusion CST4 and VEGF-A are higher expressed in ESCC tissues than normal tissues.They are involved in the development and metastasis of ESCC,and they are expected to be important indicators for the treatment and prognosis of ESCC.

Objective To investigate the impact of usnic acid on neuronal necroptosis in rats with cerebral infarction by regulating the receptor-interacting protein kinase 1(RIPK1)/receptor-interacting protein kinase 3(RIPK3)/mixed lineage kinase domain-like protein(MLKL)signaling pathway.Methods The rat model of cerebral infarction was established by middle cerebral artery occlusion and reperfusion(MCAO/R).The successfully modeled rats were divided into model group,NEC-1(RIP1 inhibitor)group,low-,medium-,and high-dose of usnic acid groups,with 20 rats in each group.Another 20 rats were selected as a sham-operation group.After 3 days of drug intervention,the modified Neurological Severity Scale(mNSS)was applied to evaluate the degree of neurological damage of rats in each group.TTC staining was applied to detect the volume of cerebral infarction.HE staining was selected to observe pathological damage in brain tissue.PI/NeuN staining was selected to observe neuronal necrosis.RT-qPCR was used to detect mRNA levels of RIPK1,RIPK3 and MLKL in rat ischemic brain tissue.Western Blot was used to determine the expressions of RIPK1/RIPK3/MLKL signaling pathway related proteins in rat ischemic brain tissue.Results Compared with the sham-operation group,the neural cells in the model group showed structural damage,cell disrupted,deformation,and nuclear pyknosis,furthermore,the mNSS score,the cerebral infarction volume,proportion of PI-positive neurons were significantly increased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL in brain tissue,ratio of p-RIPK1/RIPK1,and the levels of RIPK3 and MLKL proteins were obviously increased(P＜0.05).Compared with the model group,the damage degree of neurocyte morphology in the low-,medium-,and high-dose of usnic acid groups was gradually alleviated,the nuclear membrane was gradually became clear,and the cell body was gradually returned to normal.The neurocyte morphology in the NEC-1 group was basically intact,and the nuclear membrane was basically clear.The mNSS score,cerebral infarction volume and proportion of PI-positive neurons in NEC-1 group and usnic acid groups were significantly decreased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL,ratio of p-RIPK1/RIPK1,and levels of RIPK3 and MLKL proteins in brain tissue were obviously reduced in usnic acid groups and NEC-1 group.Also,there was dose-dependent decrease in usnic acid groups(P＜0.05).No statistically obvious difference was found between the high-dose usnic acid group and the NEC-1 group(P＞0.05).Conclusion Usnic acid inhibits neuronal necroptosis in rats with cerebral infarction by inhibiting the RIPK1/RIPK3/MLKL signaling pathway,thereby alleviating brain injury in rats with cerebral infarction.

Objective:To evaluate the effectiveness of deep learning reconstruction (DLR) compared with hybrid iterative reconstruction (Hybrid IR) in improving the image quality in chest low-dose CT (LDCT).Methods:Seventy-seven patients who underwent LDCT scan for physical examination or regular follow-up in Peking Union Medical College Hospital from October 2020 to March 2021 were retrospectively included. The LDCT images were reconstructed with Hybrid IR at standard level (Hybrid IR Stand) and DLR at standard and strong level (DLR Stand and DLR Strong). Regions of interest were placed on pulmonary lobe, aorta, subscapularis muscle and axillary fat to measure the CT value and image noise. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated. Subjective image quality was evaluated using Likert 5-score method by two experienced radiologists. The number and features of ground-glass nodule (GGN) were also assessed. If the scores of the two radiologists were inconsistent, the score was determined by the third radiologist. The objective and subjective image evaluation were compared using the Kruskal-Wallis test, and the Bonferroni test was used for multiple comparisons within the group.Results:Among Hybrid IR Stand, DLR Stand and DLR Strong images, the CT value of pulmonary lobe, aorta, subscapularis muscle and axillary fat had no significant differences (all P>0.05), but the image noise and SNR of pulmonary lobe, aorta, subscapularis muscle and axillary fat had significant differences(all P<0.05), and the CNR of images had significant difference( P<0.05), too. The CNR of Hybrid IR Stand images, DLR stand images and DLR strong images were 0.71 (0.49, 0.88), 1.06 (0.78, 1.32) and 1.14 (0.84, 1.48), respectively. Compared with Hybrid IR images, DLR images had lower objective and subjective image noise,higher SNR and CNR (all P<0.05). The scores of DLR images were superior to Hybrid IR images in identifying lung fissures, pulmonary vessels, trachea and bronchi, lymph nodes, pleura, pericardium and GGN (all P<0.05). Conclusions:DLR significantly reduced the image noise, and DLR images were superior to Hybrid IR images in identifying GGN in chest LDCT while maintaining superior image quality at relatively low radiation dose levels. Thus DLR images can improve the safety of lung cancer screening and pulmonary nodule follow-up by CT.

Objective:To explore the effect of deep learning reconstruction (DLR) on radiation dosage reduction and image quality of CTPA compared with hybrid iterative reconstruction (HIR).Methods:A total of 100 patients with suspected pulmonary embolism (APE) or indications for CTPA due to other pulmonary artery diseases in Peking Union Medical College Hospital from December 2020 to April 2021 were prospectively enrolled and divided into HIR group and DLR group according to block randomization, with 50 cases in each group. The patient′s gender, age and body mass index (BMI) were recorded. HIR group and DLR group underwent standard deviation (SD)=8.8 and SD=15 CTPA protocols in combination with HIR and DLR algorithm respectively. Other scanning parameters and contrast medium injection plan were the same. The effective dose (ED) and size-specific dose estimate (SSDE) were calculated. Regions of interest (ROIs) were drawn in the lumen of Grade 1-3 pulmonary arteries and bilateral paravertebral muscles. The corresponding CT and SD values were recorded to acquire signal to noise ratio (SNR) and contrast noise ratio (CNR). Based on a double-blind method, two radiologists evaluated the subjective noise, visualization of pulmonary arteries, and diagnostic confidence of the two groups by 5-point Likert scales. The inconsistent results were judged comprehensively by the third radiologist. Independent samples t-test was used to compare the demographic data, radiation dosage and quantitative image quality of the two groups. Mann-Whitney U test was used to compare the subjective noise, visualization of pulmonary arteries and diagnostic confidence between the two groups. Linear weighted Kappa coefficient was calculated to analyze the consistency of the qualitative scores between the two radiologists. Results:There were no significant differences in gender, age and BMI between the two groups ( P>0.05). The CT values of Grade1-3 pulmonary arteries and paravertebral muscle had no significant differences ( P>0.05). Compared with HIR group, the ED and SSDE in DLR group decreased by about 35% to 1.3 mSv and 4.20 mGy respectively, while the SNR (30±5) and CNR (26±5) of CTPA images were higher in DLR group than those in HIR group (23±5 and 20±5, with t=-6.60 and -5.90, respectively, both P<0.001). The subjective noise score was higher in DLR group than that in HIR group ( Z=-7.34, P<0.001). In addition, two radiologists showed excellent interobserver agreement in DLR group (Kappa=0.847, 95%CI 0.553-1.000). No significant differences were found in visualization of pulmonary arteries and diagnostic confidence between the two groups ( P>0.05). Conclusion:DLR further reduced the radiation dosage and improved the image quality of CTPA, with no detriment to diagnostic confidence. Thus DLR is worthy of clinical promotion.

Objective:To investigate the feasibility of chest ultra-low dose CT (ULDCT) using deep learning reconstruction (DLR) for lung cancer screening, and to compare its image quality and nodule detection rate with ULDCT iterative reconstruction (Hybrid IR) and conventional dose CT (RDCT) Hybrid IR.Methods:The patients who underwent chest CT examination for pulmonary nodules in Peking Union Medical College Hospital from October 2020 to March 2021 were prospectively included and underwent chest RDCT (120 kVp, automatic tube current), followed by ULDCT (100 kVp, 20 mA). The RDCT images were reconstructed with Hybrid IR (adaptive iterative dose reduction 3D,AIDR 3D), and ULDCT was reconstructed with AIDR3D and DLR. Radiation dose parameters and nodule numbers were recorded. Image quality was assessed using objective noise, signal-to-noise ratio (SNR) of the main trachea and left upper lobe, subjective image scores of the lung and nodules. Subjective scores were scored by 2 experienced radiologists on a Likert 5-point scale. The difference of radiation dose was compared with paired t-test between ULDCT and RDCT.The differences of quantitative indexes, objective image noise and subjective scores of the three reconstruction methods were compared with one-way analysis of variance or Friedman test. Results:Forty-five patients were enrolled, including 17 males and 28 females, aged from 32 to 74 (55±11) years. The radiation dose of ULDCT was (0.17±0.01) mSv, which was significantly lower than that of RDCT [(1.35±0.41) mSv, t=15.46, P<0.001]. There were significant differences in the image noise and SNR in the trachea and lung parenchyma and in the CT value of the trachea among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images ( P<0.05). Image noise in the trachea and lung parenchyma and CT value in the trachea of ULDCT-AICE were significantly lower than those of ULDCT-AIDR 3D ( P<0.05) and comparable to RDCT-AIDR 3D ( P>0.05). There were significant differences in subjective image scores of the lung and nodules among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images (χ2=50.57,117.20, P<0.001). Subjective image scores of the lung and nodules for ULDCT-AICE were significantly higher than those of ULDCT-AIDR 3D ( P<0.05), and non-inferior to RDCT-ADIR 3D ( P>0.05). All 72 clinically significant nodules detected on RDCT-ADIR 3D were also noted on ULDCT-AICE and ULDCT-AIDR 3D images. Conclusions:Chest ULDCT using DLR can significantly reduce the radiation dose, and compared with Hybrid IR, it can effectively reduce the image noise and improve SNR, and display the pulmonary nodules well. The image quality and nodule detection are not inferior to RDCT Hybrid IR routinely used in clinical practice.