Synthesis of N-2(5H)-furanonyl sulfonyl hydrazone derivatives and their biological evaluation in vitro and in vivo activity against MCF-7 breast cancer cells.

A series of (E)-N-2(5H)-furanonyl sulfonyl hydrazone derivatives have been rationally designed and efficiently synthesized by one-pot reaction with good yields for the first time. This green approach with wide substrate range and good selectivity can be achieved at room temperature in a short time in the presence of metal-free catalyst. The cytotoxic activities against three human cancer cell lines of all newly obtained compounds have been evaluated by MTT assay. Among them, compound 5 k exhibits high cytotoxic activity against MCF-7 human breast cancer cells with an IC50 value of 14.35 µM. The cytotoxic mechanism may involve G2/M phase arrest pathway, which is probably caused by activating DNA damage. Comet test and immunofluorescence results show that compound 5 k can induce DNA damage in time- and dose-dependent manner. Importantly, 5 k also can effectively inhibit the proliferation of MCF-7 cells and angiogenesis in the zebrafish xenograft model. It is potential to further develop N-2(5H)-furanonyl sulfonyl hydrazone derivatives as potent drugs for breast cancer treatment with higher cytotoxic activity by modifying the structure of the compound.

A radiomics model of liver CT to predict risk of hepatic encephalopathy secondary to hepatitis B related cirrhosis.

PURPOSE: To build a radiomics model of liver contrast-enhanced computed tomography (CT) to predict hepatic encephalopathy secondary to Hepatitis B related cirrhosis. MATERIALS AND METHODS: This study consisted of 304 consecutive patients with first-diagnosed hepatitis B related cirrhosis. 212 and 92 patients were randomly computer-generated into training and testing cohorts, among which 38 and 21 patients endured HE, respectively. 356 radiomics features of liver were extracted from portal venous-phase CT data, and 3 clinical features were collected from medical record. After data were standardized by Z-score, we used least absolute shrinkage and selection operator to choose useful radiomics features. Ultimately, three predictive models including a radiomics model, a clinical model and an integrated model of radiomics and clinical features were built by analysis of R-software. Predictive performance was tested by multivariable logistic regression, and evaluated by area under receiver-operating characteristic curve (AUC), and accuracy. RESULTS: 19 radiomics features of liver CT were selected. The selected radiomics features and 3 relevant clinical features were applied to develop a radiomics model, a clinical model, and an integrated model of both radiomics and clinical features. The integrated model showed better performance than the radiomics model or clinical model to predict HE (AUC = 0.94 vs. 0.91 or 0.76, and 0.87 vs. 0.86 or 0.73; accuracy = 0.93 vs. 0.89 or 0.83, and 0.83 vs. 0.84 or 0.77) in the training and testing cohorts, respectively. CONCLUSION: The integrated model of radiomics and clinical features could well predict HE secondary to hepatitis B related cirrhosis.

Concordance of Chest CT and Nucleic Acid Testing in Diagnosing Coronavirus Disease Outside its District of Origin (Wuhan, China).

OBJECTIVES: This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). METHODS: Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. RESULTS: Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). CONCLUSIONS: Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.

[Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules].

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Liver lobe based intravoxel incoherent motion diffusion weighted imaging in hepatitis B related cirrhosis: Association with child-pugh class and esophageal and gastric fundic varices.

Liver cirrhosis is a common chronic progressive liver disease in clinical practice, and intravoxel incoherent motion (IVIM) is a promising magnetic resonance method to assess liver cirrhosis, so our purpose was to investigate association of liver-lobe-based IVIM-derived parameters with hepatitis-B-related cirrhosis and its severity, and esophageal and gastric fundic varices. Seventy-four patients with hepatitis-B-related cirrhotic and 25 healthy volunteers were enrolled and underwent upper abdominal IVIM diffusion-weighted imaging with b-values of 0, 20, 50, 80, 100, 200, 400, 600, and 800 s/mm. IVIM-derived parameters (D, pure molecular diffusion; D, pseudo diffusion; and f, perfusion fraction) of left lateral lobe (LLL), left medial lobe (LML), right lobe (RL), and caudate lobe (CL) were assessed statistically to show their associations with cirrhosis and its severity, and esophageal and gastric fundic varices. In this research, we found that D, D, and f values of LLL, LML, RL, and CL were lower in cirrhotic liver than in normal liver (all P-values <.05). D, D, and f values of LLL, LML, RL, and CL were inversely correlated with Child-Pugh class of cirrhosis (r = -0.236 to -0.606, all P-values <.05). D of each liver lobe, D of LLL and CL, and f of LLL, LML, and CL in patients with esophageal and gastric fundic varices were lower than without the varices (all P-values <.05). D values of RL and CL could best identify cirrhosis, and identify esophageal and gastric fundic varices with areas under receiver-operating characteristic curve of 0.857 and 0.746, respectively. We concluded that liver-lobe-based IVIM-derived parameters can be associated with cirrhosis, and esophageal and gastric fundic varices.

Concordance of chest ct and nucleic acid testing in diagnosing coronavirus disease outside its district of origin (Wuhan, China)

OBJECTIVES: This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). METHODS: Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. RESULTS: Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). CONCLUSIONS: Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.

CT radiomic features for predicting resectability of oesophageal squamous cell carcinoma as given by feature analysis: a case control study.

BACKGROUND: Computed tomography (CT) is commonly used in all stages of oesophageal squamous cell carcinoma (SCC) management. Compared to basic CT features, CT radiomic features can objectively obtain more information about intratumour heterogeneity. Although CT radiomics has been proved useful for predicting treatment response to chemoradiotherapy in oesophageal cancer, the best way to use CT radiomic biomarkers as predictive markers for determining resectability of oesophageal SCC remains to be developed. This study aimed to develop CT radiomic features related to resectability of oesophageal SCC with five predictive models and to determine the most predictive model. METHODS: Five hundred ninety-one patients with oesophageal SCC undergoing contrast-enhanced CT were enrolled in this study, and were composed by 270 resectable cases and 321 unresectable cases. Of the 270 resectable oesophageal SCCs, 91 cases were primary resectable tumours; and the remained 179 cases received neoadjuvant therapy after CT, shrank on therapy, and changed to resectable tumours. Four hundred thirteen oesophageal SCCs including 189 resectable cancers and 224 unresectable cancers were randomly allocated to the training cohort; and 178 oesophageal SCCs including 81 resectable tumours and 97 unresectable tumours were allocated to the validation group. Four hundred ninety-five radiomic features were extracted from CT data for identifying resectability of oesophageal SCC. Useful radiomic features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomic features were chosen using multivariable logistic regression, random forest, support vector machine, X-Gradient boost and decision tree classifiers. Discriminating performance was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1score. RESULTS: Eight radiomic features were selected to create radiomic models related to resectability of oesophageal SCC (P-values < 0.01 for both cohorts). Multivariable logistic regression model showed the best performance (AUC = 0.92 ± 0.04 and 0.87 ± 0.02, accuracy = 0.87 and 0.86, and F-1score = 0.93 and 0.86 in training and validation cohorts, respectively) in comparison with any other model (P-value < 0.001). Good calibration was observed for multivariable logistic regression model. CONCLUSION: CT radiomic models could help predict resectability of oesophageal SCC, and multivariable logistic regression model is the most predictive model.

Assessing Microcirculation in Resectable Oesophageal Squamous Cell Carcinoma with Dynamic Contrast-enhanced MRI for Identifying Primary tumour and Lymphatic Metastasis.

This study aimed to determine whether dynamic contrast-enhanced MRI (DCE-MRI) derived parameters can identify oesophageal squamous cell carcinoma (SCC) and lymphatic metastasis. Thirty-nine oesophageal SCC patients underwent DCE-MRI. Quantitative parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume and fractional plasma volume, and semi-quantitative parameters including time to peak (TTP), max concentration, Max Slope and area under concentration-time curve of both oesophageal SCC and normal oesophagus were measured. Mann-Whitney U test revealed that Ktrans and Kep of oesophageal SCC were higher while TTP was shorter when compared to normal oesophagus (all P-values < 0.05); and areas under receiver operating characteristic [ROC] curves displayed that Kep was superior to TTP or Ktrans for identifying oesophageal SCC (0.903 vs. 0.832 or 0.713). Mann-Whitney U test also demonstrated that Kep was higher and TTP was shorter in patients with lymphatic metastasis when compared to non-metastatic cancer patients (both P-values < 0.05), and area under ROC curve also showed that TTP was superior to Kep for predicting lymphatic metastasis (0.696 vs. 0.659). In conclusion, the combination of quantitative and semi-quantitative parameters derived from DCE-MRI can aid in the identification of oesophageal SCC and lymphatic metastasis.

Is there association of gross tumor volume of adenocarcinoma of oesophagogastric junction measured on magnetic resonance imaging with N stage?

PURPOSE: To determine whether gross tumour volume (GTV) of adenocarcinoma of oesophagogastric junction (AOG) measured on fat-suppression T2-weighted imaging (FS-T2WI) and diffusion-weighted imaging (DWI) correlates with regional lymph node metastasis and N stage. MATERIALS AND METHODS: The study was approved by the institutional ethics committee, and written informed consent was obtained. Forty-six patients with AOG underwent preoperative magnetic resonance scans including FS-T2WI and DWI with b-values of 500 and 800 s/mm2. GTV was measured on FS-T2WI and DWI. Statistical analyses were performed to determine association of GTV with N stage. RESULTS: Univariate analysis showed GTV measured on FS-T2WI and DWI with b-values of 500 and 800 s/mm2 were correlated with lymph node metastasis (all Ps < 0.05). Spearman rank correlation tests demonstrated a trend toward an increase in GTV obtained on previous sequences with increasing N stage (r = 0.578 to 0.591, all Ps < 0.001). Mann-Whitney U tests showed GTV obtained on previous sequences could distinguish grouped N stages (all Ps < 0.05). Receiver operating curve analyses demonstrated that GTV obtained on FS-T2WI and DWI with b-value of 500 s/mm2 and DWI with b-value of 800 s/mm2 might differentiate stage N0 from stages N1-3 (cutoff, 19.70 cm3, 16.70 cm3 and 12.24 cm3, respectively), stages N0-1 from N2-3 (cutoff: 22.16 cm3, 17.54 cm3 and 14.17 cm3, respectively), stages N0-2 from N3 (cutoff: 25.57 cm3, 29.27 cm3 and 22.73 cm3, respectively). CONCLUSION: There is a trend toward an increase in GTV obtained on FS-T2WI and DWI sequences with increasing N stage.

Magnetic Resonance Diffusion Kurtosis Imaging for Evaluating Stage of Liver Fibrosis in a Rabbit Model.

RATIONALE AND OBJECTIVES: As an extension of the conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI) is based on the non-Gaussian diffusion model that can inherently account for restricted water diffusion within the complex microstructure of most tissues. This study aimed to investigate association of liver DKI derived parameter with stage of liver fibrosis. MATERIALS AND METHODS: Fifty-six healthy New Zealand white rabbits were enrolled into this study, among which 48 rabbits were randomly given carbon tetrachloride to model liver fibrosis, and 8 rabbits treated with normal saline served as control subjects. All rabbits underwent liver DKI followed by biopsy to stage fibrosis (stages F0-F4) on 6th, 8th, 10th, and 12th weekends after initiation of modeling fibrosis. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusion (MD) were derived from DKI data. Statistical analysis was to evaluate association of DKI derived parameter with stage of fibrosis. RESULTS: FA (r = 0.512) and MK (r = 0.567) increased, and MD (r = -0.574) decreased with increasing stage of fibrosis from F0 to F4 (all p values < 0.05). Significant differences were found in all parameters between F0 and F3 or F4, F1 and F4, F0 and F1-4, and F0-1 and F2-4 (all p values < 0.05). FA and MD could distinguish between F0 from F2, MD, and MK could distinguish F1 from F3, F0-2 from F3-4, and F1-2 from F3-4, and MK and FA could distinguish F2 from F4, and F0-3 from F4 (all p values < 0.05). According to receiver operating characteristic analysis, MK could best predict stage ≥F1, ≥F2, ≥F3, and F4, and discriminate F1-2 from F3-4 with areas under receiver operating characteristic curve of 0.766-0.930. CONCLUSION: DKI derived parameters can help stage fibrosis.

Tumour volume of resectable oesophageal squamous cell carcinoma measured with MRI correlates well with T category and lymphatic metastasis.

OBJECTIVES: To determine association of gross tumour volume (GTV) of resectable oesophageal squamous cell carcinoma (SCC) measured on T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE-T1WI) and diffusion-weighted imaging (DWI) with T category and lymphatic metastasis (LM). METHODS: Sixty oesophageal SCC patients underwent fat-suppressed T2WI, CE-T1WI and DWI with b values of 0, 500 and 800 s/mm2. GTV was measured on three sequences. Statistical analyses were performed to determine association of GTV with T category and LM. RESULTS: Spearman's rank correlation analysis showed positive association of GTV with T category and LM (all p values < 0.01). Differences in GTV were found between T1 and T2 or T3 categories shown by Kruskal-Wallis H and one-way ANOVA tests, and between T1/T2 and T3 and between tumours with and without LM by Mann-Whitney U tests (all p values < 0.05). Receiver operating characteristic analyses showed cut-off GTVs of 5.795, 5.276 and 10.11 cm3 on CE-T1WI could better differentiate T1 from T2 categories, T1 from T3, and T1-2 from T3 than those of 7.066, 7.045 and 8.504 cm3 on T2WI, of 5.793, 6.609 and 6.989 cm3 on DWI with b value of 500 s/mm2, and of 4.156, 4.519 and 4.985 cm3 with b value of 800 s/mm2, respectively. Cut-off of 10.462 cm3 on DWI with b value of 500 s/mm2 could better identify LM than of 12.38, 8.793 and 9.600 cm3 on T2WI, CE-T1WI and DWI with b value of 800 s/mm2, respectively. CONCLUSIONS: GTVs on T2WI, CE-T1WI and DWI are associated with T category of and LM of oesophageal SCC. KEY POINTS: • GTV is associated with T category and lymphatic metastasis of oesophageal SCC • GTV measured on contrast-enhanced T 1 -weighted imaging better identifies T category • GTV measured on DWI with b value of 500 s/mm 2 better identifies lymphatic metastasis.

[Prescription design and dissolution evaluation of self-emulsifying drug delivery systems of baicalin].

OBJECTIVE: To improve dissolution and bioavailability of baicalin in solid prescription and screen the prescription of self-emulsifying drug delivery systems of baicalin. METHODS: Orthogonal test was applied to optimize the prescription of self-emulsifying drug delivery systems of baicalin, and the best prescription was selected by comprehensive evaluation of emulsion speed, size and light transmission rate. RESULTS: The best quantity ratio of self-emulsifying drug delivery systems of baicalin was baicalin: polysorbate 80: oliver oil: glycerol = 0.15 : 1 : 1 : 1.5. CONCLUSION: Self-emulsifying drug delivery systems of baicalin prepared can effectively improve the dissolution of baicalin in artificial gastric juice.