Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective:To understand and explore the incidence and influencing factors of malnutrition in patients with inflammatory bowel disease.Methods:This study was a cross-sectional study. Patients with inflammatory bowel disease hospitalized in the Department of Gastroenterology of a tertiary hospital in Shenzhen from March 1 to August 31, 2021 were enrolled. Indicators related to nutrition and clinical outcome were collected, including height, weight, body mass index (BMI), nutritional risk screening (NRS 2002) results, malnutrition diagnosis as per Global Leadership Initiative on Malnutrition (GLIM) criteria and Pittsburgh Sleep Quality Index (PSQI). Chi-square test, t-test and Wilcoxon rank sum test were used as appropriate for univariate analysis, and binary logistic regression analysis was used for multivariate analysis.Results:A total of 188 patients were included in this survey. There were 145 (77.1%) patients with no malnutrition, 38 (20.2%) with moderate malnutrition, and 5 (2.7%) with severe malnutrition according to GLIM criteria. In the subgroup of 47 ulcerative colitis patients, 12 (25.5%) were with moderate malnutrition and 3 (3.4%) were with severe malnutrition. In the subgroup of 141 Crohn's disease patients, 26 (18.4%) were with moderate malnutrition and 2 (1.4%) were with severe malnutrition. When divided by the presence or absence of malnutrition, there were statistically significant differences in age ( t = -2.237, P = 0.026), disease stage ( χ 2 = 22.299, P < 0.001), history of digestive tract resection ( χ 2 = 6.890, P = 0.009), intestinal infection ( χ 2 = 4.010, P = 0.045), gastrointestinal symptoms ( χ 2 =11.884, P = 0.001), hemoglobin ( t = 5.160, P < 0.001), serum albumin ( t = 3.96, P < 0.001), prealbumin ( t = 5.061, P < 0.001) and PSQI scores ( t = -4.744, P < 0.001). Multivariate analysis showed that the stage of disease, history of partial resection of digestive tract, gastrointestinal symptoms, hemoglobin, prealbumin and PSQI scores were the main influencing factors of malnutrition. Conclusions:IBD patients at older age, at active stage, and with history of partial digestive tract resection, intestinal infection, gastrointestinal symptoms, low hemoglobin, low serum albumin, low prealbumin and poor sleep quality are more likely to develop malnutrition. Timely intervention should be carried out to improve the nutritional status of these patients.

【Objective:】 To summarize the research status, problems and countermeasures of ethical issues related to volunteer action in public health emergencies by reviewing relevant literature. 【Methods:】 Using four keywords: public health emergencies, volunteers, ethics, and research, this paper searched the Chinese and English databases for the literature published from December 2006 to December 2021 (15 years in total) on "ethical research on volunteer action in public health emergencies". After searching, it was found that there were not many related papers. A total of 31 papers were retrieved, and only 23 papers were selected. 【Results:】 The ethical problems faced by volunteers in public health emergencies were complex and diverse, and the individual ethical behavior of volunteers was affected by many factors. The strategies to solve the relevant ethical issues were not yet perfect. 【Conclusions:】 The ethical issues related to volunteer actions in public health emergencies needed to be further studied.

Objective:To evaluate the objective imaging markers of cognitive impairment in patients with end-stage renal disease by MRI intravoxel incoherent motion.Methods:A total of 40 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to August 2020, and 24 healthy controls were prospectively enrolled at the same time.All subjects performed with MRI scan were collected, and the slow apparent diffusion coefficient (ADC slow) of the corresponding brain regions were obtained .The cognitive function was evaluated by the Montreal cognitive assessment scale (MoCA). Two-sample t test was used to analyze the difference of ADC slow and cognitive score between the two groups.Pearson correlation analysis was performed among the cognitive function score of end-stage renal disease and ADC slow value. Results:(1) The score of the intelligence test scale in the ESRD group (23.30±1.76) was significantly lower than that of the healthy control group (27.92±1.00) ( P<0.01). The ADC slow values of bilateral frontal lobe, hippocampus, and insula brain areas (respectively(0.648±0.035), (0.633±0.043), (0.762±0.043), (0.756±0.042), (0.792±0.048), (0.776±0.054))in the ESRD group were significantly higher than those in the healthy control group ((0.600±0.039), 0.610±0.037, (0.725±0.059), (0.711±0.054), (0.740±0.063), (0.716±0.051)) ( P<0.01). (2) Pearson correlation analysis showed that the ADC slow values of bilateral insula and right hippocampus in the ESRD group were negatively correlated with MoCA scales ( r=-0.38, -0.38, -0.66, all P<0.05). Conclusion:ADC slow value in IVIM can better reflect the changes of cognitive function impairment in ESRD patients.

Objective: To determine the transdermal absorption of phloretin and ligustilide in Fufang phloretin cream.Methods: In vitro percutaneous absorption test using the Franz intelligent transdermal absorption apparatus was adopted, an HPLC method was used to determine the contents of phloretin and ligustilide in the accepting solution at different time points, and then the cumulative release amount and the total penetration amount were calculated to evaluate the percutaneous absorption behavior.Results: Phloretin and ligustilide showed a good linearity within the range of 0.044 2-4.42 μg·ml-1(r=0.999 9) and 0.048 7-4.87 μg·ml-1(r=0.999 9), respectively, the average recovery was 99.85% and 99.92%, and RSD was 0.67% and 0.66% (n=9), respectively.The in vitro permeation behavior of phloretin and ligustilide through the skin of rats fit Higuchi equations(r>0.9), suggesting a good linear correlation between the cumulatine penetration amount (Qn) and (time).Conclusion: Fufang phloretin cream has a good percutaneous permeation property in vitro.

Objective To identify the circulating miRNAs which can be used to evaluate the diagnosis and prognosis of sepsis by microarray and quantitative real-time PCR,and to predict target genes of miR-519c-5p by bioinformatics analysis. Methods Three sepsis patients,3 septic shock patients and 3 normal controls were enrolled in this study. Plasma RNA was extracted,and was used for hybridized by miRCURY LNATMmicroRNA Array.The signals were scanned and used to conduct differential expression profilings and cluster analysis.Further-more,we performed qRT-PCR to confirm the expression of miRNAs chosen from microarray screening. We used the miRanda and Targetscan databases to predict target genes of the concerned miRNAs and used KEGG database to analyze the related pathways. Results Fifty-seven and 11 miRNAs were observed significantly upregulated in sepsis and septic shock patients,respectively(fold change≥2.0;P<0.05).qRT-PCR results showed that miR-519c-5p was significantly upregulated in patients with sepsis or patients with septic shock compared with the healthy normal controls(P<0.05).Twenty-nine target genes of miR-519c-5p were predicted by the bioinformatics analysis,and 7 potential target genes participate in the sepsis-related pathways.MiR-519c-5p might be a potential positive regulator for the critical cell cycle control gene of MAP2K4,contributing to the vascular endothelial cells apoptosis via MAPK signaling pathway. Conclusions We demonstrated that the plasma level of miR-519c-5p can be used for the diagnosis of sepsis and miR-519c-5p may be a potential therapeutic target for sepsis.

Aim To explore the relationship between IL-8 and ELMO1 in breast carcinoma and the mecha-nisms of IL-8 induced invasion and metastasis. Meth-ods Under the IL-8 stimulation, chemotaxis assay was examined to detect the chemotaxis ability of breast cancer cell line MDA-MB-231 and MCF-7 . ELMO1 protein levels in breast cancer cell lines were detected using Western blot. MDA-MB-231 cells were transfect-ed with small RNA interference plasmids in order to downregulate ELMO1 expression, and overexpression plasmids were used to upregulate the expression of EL-MO1 in MCF-7 cells. Matrigel invasion assay and chemotaxis assay were used to detect the in vitro inva-sion and chemotaxis ability of breast cancer cells with IL-8 stimulation. Results IL-8 induced chemotaxis of the different breast cancer cell lines in a dose-depend-ent manner. After transient transfection, Western blot results showed that ELMO 1 protein levels observably decreased in SiELMO1/MDA-MB-231 cells compared with Scr/MDA-MB-231 cells, while the expression of ELMO1 protein levels significantly increased in MCF-7/ELMO1 cells compared with the MCF-7/Con cells;with IL-8 stimulation, SiELMO1/MDA-MB-231 cells showed significantly decreased chemotaxis ability com-pared with Scr/MDA-MB-231 cells. MCF-7/ELMO1 cells showed significantly increased chemotaxis ability compared with MCF-7/Con cells; the invasion assay showed under the stimulation of IL-8 , and the invasion ability was significantly reduced in SiELMO1/MDA-MB-231 cells compared with Scr/MDA-MB-231 cells ( P<0. 05 ) . The invasion ability was significantly en-hanced in MCF-7/ELMO1 cells compared with MCF-7 cells( P<0. 05 ) . Conclusion IL-8 promotes the in-vasion and migration of breast cancer cells MDA-MB-231 and MCF-7 , and ELMO1 plays an important role in IL-8 induced chemotaxis and invasion.

Objective To explore the image quality and radiation dose for coronary angiography using DSCT (dual-source computed tomography) under lower tube voltage and lower contrast agent concentration ('double low').Methods A total of 160 patients with suspected coronary artery disease underwent dual-source CCTA.80 patients (BMI ＜ 25 kg/m2) were randomly assigned to group A (270 mg I/ml-80 kV) and B (350 mg I/ml-120 kV).The other 80 patients (25 ≤ BMI ＜30 kg/m2) were randomly assigned to group C (270 mg I/ml-100 kV) and D (350 mg I/ml-120 kV),sonogram affirmed iterative reconstruction technology and 270 mg I/ml contrast agent were applied to group A and C ; FBP technology and 350 mg I/ml contrast agent were applied to group B and D.Adaptive cardio-sequence prospective ECG-gated technology was applied in all patients,while the acquisition phase was 65％-75％ RR interval (when heart rate ＜ 75 beats / min) or 40％-50％ RR interval at when heart rate ≥ 75 beats/min.Volume CT dose index (CTDIvol),dose length product (DLP),effective dose (E),size specific dose estimates (SSDE),image noise,CT value,signal-to-noise ratio (SNR),and contrast-to-noise ratio(CNR) were all evaluated for each patient.Results There was not statistical difference in scan length among groups A and B,C and D.There was statistical difference in tube current between group A and B (t =8.932,P ＜0.05).There was not statistical difference in tube current between group C and D (tCD =-1.212,P ＞ 0.05).There was statistical difference in CTDIvol,DLP,E and SSDE between group A and B,C and D (tCTDIvol =-16.141,-11.440 ; tDLP =-17.454,-10.521 ; t =-17.444,-10.523 ;tSSDE =-13.032,-9.119,P ＜0.05).Compared to group B,the SSDE in group A decreased by 64.4％.Compared to group D,the SSDE in group C decreased by 39.3％.There was no statistical difference in image noise between group A and B,C and D (P ＞ 0.05).There was statistical difference in CT value,SNR and CNR between group A and B (t =0.436,4.623,3.272,P ＜ 0.05).There was no statistical difference in CT value and CNR between group C and D,while there was statistical difference in SNR between group C and D (t =2.981,P ＜0.05).There was no statistical difference in image quality scores between group A and B,C and D (P ＞ 0.05).Conclusion Compared with conventional DSCT coronary angiography,'double low' DSCT coronary scanning solution can significantly reduce the radiation dose and contrast agent,and could provide the effective coronary images which meet the clinical diagnostic needs.

Objective To explore the feasibility of “double low ”(low tube voltage and low contrast agent concentration)imaging technology of dual-source computed tomography (DSCT)in coronary angiography for low-weight patients.Methods 60 patients (BMI≤25 kg/m2 )who underwent coronary CT angiography (CCTA)on DSCT scanner were divided randomly into 2 groups:group A was “double low”group (n = 30,tube voltage = 80 kVp,using sinogram affirmed iterative reconstruction technology and 270 mg I/mL concentration of contrast agent);Group B was conventional group (n=30,tube voltage=120 kVp,using filtered back projection technology and 350 mg I/mL concentration of contrast agent).Adaptive cardiosequence prospective ECG-gated technology (CorAdSeq)was applied in both the groups,The collecting phase was 65%-75% RR interval (when heart rate<70 beats per mi-nute)or 40%-50% RR interval (when heart rate≥70 beats per minute).Subjective and objective methods were applied to evaluate the image quality.The image quality and.radiation dose were compared between the “double low”group and the conventional group by using SPSS 1 9.0 software.The differences between measurement data were analyzed by using independent samples t-test.Results The effective dose with size specific dose estimates (EDssde)of group A(1.22±0.31)mGy/cm was significantly lower than that of group B (3.44±0.80)mGy/cm with P <0.001.Contrast-noise ratio,signal-noise ratio and CT value of group A were signifi-cantly higher than those of group B (all P <0.05 ).Conclusion Compared with conventional DSCT coronary angiography,“double low”DSCT coronary scanning proposal for low-weight patients can significantly reduce the radiation dose and the amount of contrast agent,and the image quality can meet the needs of clinical diagnosis.

Objective To compare the iodine intake,image quality and radiation dose of dual-source CT coronary artery angiography between the low concentration isotonic contrast agent with iterative reconstruction technique of sinogram affirmed iterative rEconstruction (SAFIRE) and common concentration contrast agent with filtered back projection (FBP).Methods One hundred patients [58 men,42 women; age:(62± 11)y] were enrolled in this study.Fifty consecutive patients (Group A) were scanned with FBP and common concentration contrast agent and another 50 consecutive patients (Group B) were scanned with low concentration isotonic contrast agent and iterative reconstruction technique.The image quality were assessed by two experienced radiologists with a double blinded fashion in a five score scale.The attenuation of coronary artery,scan time,imaging noise,signal-to-noise ratio (SNR),contrast-to-noise ratio (CNR),radiation dose and iodine intake between these two groups were compared using two sample t test.The observer agreement for image quality was calculated using Kappa statistics.Results All examinations were completed successfully.There was no statistical difference (P＞0.05) between two groups in clinical characteristics and scan parameters.There was no statistical difference for the mean subjective image quality of group A (4.4±0.7) and group B (4.3±0.8) (t=0.924,P＞0.05).The Kappa value between two radiologists was 0.887 (P＜0.01)on image quality.The mean attenuation of coronary artery segments was higher than 300 HU,especially in group A (386.1±51.5) HU,which was slightly higher than the group B (384.1±77.1) HU,but there was no statistical difference (t=0.157,P＞0.05).The SNR and CNR in two groups did not have significant differences (P＞0.05).The total iodine and iodine injection rates were 21.0 g,17.5 g/s in Group A and 16.2 g,13.5 g/s in Group B,respectively.The iodine intake was decreased by 22.9％ in Group B.The effective radiation dose in Group B (1.09±0.19) mSv was significantly (t=20.260,P＜0.01) lower than that in Group A (2.85±0.59) mSv,with the radiation dose reduced by 61.8％.Conclusion Low concentration isotonic contrast agent and iterative reconstruction technique can significantly reduce the radiation dose and iodine intake in CT coronary artery angiography and achieve the same image quality using common concentration contrast agent with FBP.