Ground-glass nodule (GGN) lung cancer often progresses slowly in clinical and there are few clinical studies on long-term follow-up of patients with operable GGN lung cancer treated with stereotactic body radiation therapy (SBRT). We present a successful case of GGN lung cancer treated with SBRT, but a new GGN was found in the lung adjacent to the SBRT target during follow-up. The nodule progressed rapidly and was confirmed as lung adenocarcinoma by surgical resection. No significant risk factors and related driving genes were found in molecular pathological findings and genetic tests. It deserves further study whether new GGN is related to the SBRT. This case suggests that the follow-up after SBRT should be vigilant against the occurrence of new rapidly progressive lung cancer in the target area and adjacent lung tissue.
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Humans ; Lung Neoplasms/pathology* ; Radiosurgery ; Retrospective Studies ; Adenocarcinoma of Lung/surgery* ; Lung/pathology*

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.

Objective To explore the value of CT radiomics combined with clinical data and CT features for predicting TNM stage of thymic epithelial tumor(TET).Methods Data of 216 single TET patients confirmed by surgical pathology were retrospectively analyzed.Totally 151 cases with TNM stage Ⅰ TET were divided into early group,while 27 with TNM stage Ⅲ and 38 with TNM stage Ⅳ TET were divided into late group(n=65).Univariate analysis was used to analyze clinical data and chest CT manifestations.Based on non-contrast-enhanced CT(NECT)and contrast-enhanced CT(CECT),the best radiomics features were extracted and screened to establish radiomics models(RMNECT,RMCECT)for predicting TNM stage of TET.RMNECT-clinic,RMCECT-clinic,RMNECT-clinic-CT and RMCECT-clinic-CT were constructed based on combination of clinical and CT features being significantly different between groups,respectively.The patients were divided into training set(n=151)and validation set(n=65)at the ratio of 7∶3.The above models were trained in the training set using repeated 5-fold cross validation method,and their efficacy were verified in the validation set.Results Significant differences of clinical symptoms and CT manifestations including fat infiltration around the lesion,mediastinal lymph node enlargement and pleural effusion were found between groups(all P＜0.05).Based on NECT and CECT,2 and 9 best radiomics features were selected to construct the corresponding models.In validation set,the area under the curve(AUC)of RMNECT-clinic-CT for predicting TNM stage of TET(0.864)was higher than that of RMNECT and RMNECT-clinic(AUC=0.634,0.721,Z=3.081,2.937,P=0.002,0.003),while AUC of RMCECT-clinic-CT(0.920)was also higher than that of RMCECT and RMCECT-clinic(AUC=0.689,0.751,Z=2.698,2.390,P=0.007,0.017).Conclusion CT radiomics combined with clinical data and CT features could effectively predict TNM stage of TET.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.

Objective To test the reliability and validity of the Chinese version of the Nine-Item Avoidant/Restrictive Food Intake Disorder Scale (NIAS) in patients with inflammatory bowel disease (IBD). Methods Based on convenience sampling method, 304 patients from the Treatment Center for Inflammatory Bowel Disease of two Grade Ⅲ Level hospitals A in Jiangsu Province were selected as the research objects, and they were investigated by a general information questionnaire, NIAS, and the Satisfaction with Food-Related Life (SWFL). Item analysis (discrimination analysis, correlation coefficient) and reliability analysis of the total scale and subscales (Cronbach's α coefficient) were performed. Exploratory factor analysis, confirmatory factor analysis, criterion-related validity, convergent validity, and discriminant validity were used to test the validity of the scale. Results The Chinese version of NIAS contained 9 items, including 3 subscales of picky eating, appetite and fear; the confirmatory factor analysis indicated a good construct validity in 3-factor model[χ²/df=2.340, root mean square error of approximation (RMSEA)=0.078, standardized root mean square residual (SRMR)=0.046, incremental fit index (IFI)=0.969, comparative fit index (CFI)=0.969, normed fit index (NFI)=0.948, goodness of fit index (GFI)=0.951, the Tucker-Lewis index (TLI)=0.951]; the correlation coefficient between the total score of the Chinese version of NIAS and the SWFL scale was -0.353, indicating a strong correlation; the aggregated validity CR values for each dimension of the scale were 0.821 to 0.855, and the AVE values were 0.606 for appetite, 0.621 for picky eating, and 0.664 for fear. The total Cronbach's α coefficient of the Chinese version of the NIAS scale was 0.82, and the Cronbach's α coefficients for dimensions of picky eating, appetite and fear were 0.87, 0.71 and 0.92 respectively, indicating the Chinese version of the NIAS scale had good internal consistency and stability. Conclusion The Chinese version of the NIAS scale has good reliability and validity, and can be used to evaluate avoidant and restrictive food intake disorder behaviors in IBD patients.

Objective:To evaluate the safety of leadless pacemaker implantation in super-elderly patients.Methods:Eleven patients with average age of 90 (86, 92) years who underwent leadless pacemaker implantation in the Department of Cardiology, Peking University People′s Hospital from March 2021 to May 2022 were included. The clinical data and implantation information were collected. The complications (cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection, femoral vein hematoma) and death of patients were documented at 24 h, 3 d, and 1, 3, 6 months after pacemaker implantation.Results:There were 9 males and 2 females with the body mass index of 21(19, 23)kg/m 2. The underlying diseases were hypertension, diabetes, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, previous cerebral infarction and moderate to severe tricuspid regurgitation in 9, 9, 9, 6, 4, 4, 4 patients, respectively. The left ventricular ejection fraction was 49% (45%, 52%), the hemoglobin concentration was 118 (114, 122)g/L, 4 patients were taking anticoagulant drugs, and 6 patients were taking antiplatelet drugs. Eight patients were newly implanted with a leadless pacemaker, 2 patients were implanted after removal the old ones, and 1 case was implanted at the same time as removal. The implantation time was 45(40, 47) minutes, the X-ray exposure time was 14 (13, 15) minutes, the release time was 1 (1, 2), the threshold value was 0.50(0.38, 0.75)V/0.24 ms, the impedance was 730 (700, 770) Ω, and the perceived R-wave amplitude 8.2(6.7, 12.8) mV. During the follow-up period of 8 (6, 10) months, no patient had pacemaker dysfunction; and the threshold, R wave sensing, and impedance were stable and maintained within the normal range. No cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection or death occurred perioperatively and during the follow-up period; 1 patient had hematoma after femoral vein puncture, which improved after compression treatment. Conclusion:This single-center and small-sample study shows that leadless pacemaker implantation is safe for super-elderly patients.

Objective:To explore the relationship between lipid accumulation product (LAP) and disease activity, nutritional status in patients with Crohn disease (CD).Methods:The clinical data of 74 patients with CD in the Affiliated Hospital of Yangzhou University from July 2020 to June 2021 were retrospectively analyzed. The patients were divided into active group (32 cases) and remission group (42 cases) according to simplified Crohn disease activity index (CDAI). The general clinical data, laboratory examination results and body fat indexes were recorded, body fat indexes including body mass index (BMI), waist circumference, waist-to-height ratio, LAP and nutritional risk screening 2002 (NRS2002) score. Spearman method was used for correlation analysis; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of LAP in predicting the disease activity and nutritional status in patients with CD.Results:The proportion of males, body weight, hemoglobin, albumin, total cholesterol, triglyceride and high-density lipoprotein cholesterol in active group were significantly lower than those in remission group: 46.9% (15/32) vs. 71.4% (30/42), (53.58 ± 8.13) kg vs. (61.05 ± 9.38) kg, (109.94 ± 23.70) g/L vs. (134.19 ± 18.03) g/L, (34.01 ± 5.71) g/L vs. (39.15 ± 4.27) g/L, (3.23 ± 0.68) mmol/L vs. (3.66 ± 0.74) mmol/L, (1.12 ± 0.36) mmol/L vs. (1.34 ± 0.55) mmol/L and (0.91 ± 0.23) mmol/L vs. (1.04 ± 0.33) mmol/L, the nutritional risk rate, platelet count, C-reactive protein and erythrocyte sedimentation rate were significantly higher than those in remission group: 68.8% (22/32) vs. 19.0% (8/42), (317.97 ± 130.19) ×10 9/L vs. (194.00 ± 51.91) × 10 9/L, 14.15 (6.15, 41.35) mg/L vs. 1.51 (0.22, 5.58) mg/L and 40.00 (20.50, 64.25) mm/1 h vs. 9.00 (3.00, 20.00) mm/1 h, and there were statistical differences ( P<0.01 or <0.05); there were no statistical difference in age, height, total protein and low-density lipoprotein cholesterol between the two groups ( P>0.05). The BMI, waist circumference, waist-to-height ratio and LAP in active group were significantly lower than those in remission group: 19.46 (17.70, 21.45) kg/m 2 vs. 21.08 (18.87, 23.12) kg/m 2, (72.51 ± 5.92) cm vs. (77.67 ± 7.27) cm, 0.44 ± 0.03 vs. 0.46 ± 0.04, 13.42 (5.07, 17.72) cm·mmol/L vs. 15.49 (9.37, 31.71) cm·mmol/L, the NRS2002 was significantly higher than that in remission group: 3.00 (1.00, 3.75) scores vs. 1.00 (0, 2.00) scores, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that LAP was positively correlated with BMI, waist circumference and waist-to-height ratio ( r = 0.701, 0.766 and 0.829; P<0.01); LAP was negatively correlated with NRS2002 score, platelet count and erythrocyte sedimentation rate ( r =- 0.609, - 0.249 and - 0.243; P<0.01 or<0.05). ROC curve analysis result showed that the areas under the curve of LAP predicting disease remission and nutritional status improvement in patients with CD were 0.645 and 0.832 (95% CI 0.520 to 0.770 and 0.739 to 0.925), the best cut-off values were 20.89 and 12.86 cm·mmol/L, the sensitivities were 45.2% and 81.8%, and the specificities were 87.5% and 73.3%. Conclusions:LAP has good predictive value for disease remission and nutritional status improvement in patients with CD.