Research advances in Zein-based nano-delivery systems.

Zein is the main vegetable protein from maize. In recent years, Zein has been widely used in pharmaceutical, agriculture, food, environmental protection, and other fields because it has excellent biocompatibility and biosafety. However, there is still a lack of systematic review and research on Zein-based nano-delivery systems. This paper systematically reviews preparation and modification methods of Zein-based nano-delivery systems, based on the basic properties of Zein. It discusses the preparation of Zein nanoparticles and the influencing factors in detail, as well as analyzing the advantages and disadvantages of different preparation methods and summarizing modification methods of Zein nanoparticles. This study provides a new idea for the research of Zein-based nano-delivery system and promotes its application.

STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma.

Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay, apoptosis assay, soft agar growth assay, and tumor animal model showed STEAP4 inhibited cisplatin resistance. Mechanism analysis showed STEAP4 inhibited PI3K/AKT pathway through directly interacting with AKT. Double knockdown of STEP4 and AKT significantly inhibited cisplatin resistance. We also found STEAP4 expression was negatively correlated with PI3K/AKT pathway activity in clinic specimens. In summary, our findings suggested STEAP4 inhibited cisplatin resistance through suppressing PI3K/AKT pathway activity, providing a target for HCC therapy.

Research on the hemostasis and coagulation effects of Callicarpa nudiflora based on the spectrum-effect relationship.

Callicarpa nudiflora (C. nudiflora) is widely used in the treatment of bleeding related diseases. However, its main material basis has not been fully defined which limits the in-depth study of screening out the material basis of hemostasis and coagulation from C. nudiflor. In this study, the method of spectrum-effect relationship was used to quickly screen the material basis of hemostasis and coagulation. The five compounds related to hemostasis and coagulation were screened as Alyssonoside (P24), Luteolin (P25), Quercetin (P26), Apigenin (P28), Isorhamnetin (P29). And the contribution of these five peaks to hemostasis and coagulation efficacy was P24 > P25 > P28 > P26 > P29.

Carbonic Anhydrase IX Targeting Mn(II)-Based Magnetic Resonance Molecular Imaging Probe for Hypoxia Tumors.

Physiological hypoxic conditions in the tumor microenvironment and consequential overexpression of carbonic anhydrase IX (CA IX) are two characteristics shared by numerous types of solid malignant tumors. Early detection with hypoxia assessment is crucial to improve the prognosis and therapy outcomes of hypoxia tumors. Herein, using acetazolamide (AZA) as a CA IX-targeting moiety, we design and synthesize an Mn(II)-based MR imaging probe (named AZA-TA-Mn) incorporating AZA and two Mn(II) chelates of Mn-TyEDTA on a rigid triazine (TA) scaffold. The per Mn relaxivity of AZA-TA-Mn is 2-fold higher than its monomeric Mn-TyEDTA, which allows it for low-dose imaging of hypoxic tumors. In a xenograft mice model of esophageal squamous cell carcinoma (ESCC), a low dosage of AZA-TA-Mn (0.05 mmol/kg) can selectively produce prolonged and stronger contrast enhancement in the tumor compared to the non-specific Gd-DTPA (0.1 mmol/kg). A competition study of co-injection of free AZA and Mn(II) probes confirms the in vivo tumor selectivity of AZA-TA-Mn, resulting in a more than 2.5-fold decreased tumor-to-muscle contrast-to-noise ratio (ΔCNR) at 60 min post-injection. MR imaging results were further supported by the quantitative analysis of Mn tissue levels, as the co-injection of free AZA resulted in significantly reduced Mn accumulation in tumor tissues. Finally, immunofluorescence staining of tissue sections confirms the positive correlation between the tumor accumulation of AZA-TA-Mn and CA IX overexpression. Hence, using CA IX as the hypoxia biomarker, our results illustrate a practical strategy for the development of novel imaging probes for hypoxic tumors.

Oncogenic zinc finger protein ZNF687 accelerates lung adenocarcinoma cell proliferation and tumor progression by activating the PI3K/AKT signaling pathway.

BACKGROUND: Zinc finger protein 687 (ZNF687) has previously been discovered as a potential oncogene in individuals with giant cell tumors of the bone, acute myeloid leukemia, and hepatocellular carcinoma. However, its role and mechanism in lung adenocarcinoma (LUAD) remain unclear. METHODS: In LUAD cells, tumor, and matched adjacent tissue specimens, quantitative real-time RT- polymerase chain reaction (qRT-PCR), western blotting analyses, and immunohistochemistry staining (IHC) were conducted. Cell counting kit-8 (CCK8) assay, clonogenicity analysis, flow cytometry, and transwell assays were utilized to detect ZNF687 overexpression and knockdown impacts on cell growth, colony formation, cell cycle, migration, and invasion. Bioinformatic studies, qRT-PCR and western blotting studies were employed to validate the underlying mechanisms and signaling pathways implicated in the oncogenic effect of ZNF687. RESULTS: This study demonstrated that ZNF687 expression was elevated in LUAD cells and tissues. Individuals with upregulated ZNF687 had a poorer prognosis than those with downregulatedZNF687 (p < 0.001). ZNF687 overexpression enhanced LUAD growth, migration, invasion and colony formation, and the cell cycle G1-S transition; additionally, it promoted the epithelial-mesenchymal transition (EMT). In contrast, knocking down ZNF687 showed to have the opposite impact. Moreover, these effects were associated with the activity of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling mechanism. CONCLUSION: ZNF687 was upregulated in LUAD, and high ZNF687 expression levels are associated with poor prognoses. The activation of the PI3K/AKT signaling pathway by upregulated ZNF687 increased the proliferation of LUAD cells and tumor progression. ZNF687 may be a beneficial predictive marker and a therapeutic target in LUAD.

Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application.

Amphotericin B (AmB) is regarded as a first-line therapy against life-threatening invasive fungal infections. Due to its poor oral bioavailability, AmB is restricted to intravenous administration in clinical practice. As science continues to move forward, two lipid-based formulations are successfully developed for oral AmB administration, currently undergoing phase I clinical trials. Encouragingly, lipid-AmB conjugates with emulsions also exhibit a better bioavailability, which may be another strategy to design oral AmB formulation in clinical practice. Thus, this review mainly focused on the two lipid-based formulations in clinical trials, and discussed the potential perspectives of AmB-lipid conjugation-loaded nanocochleates and emulsions.

A novel biflavone from Reineckia carnea induces apoptosis of human renal cancer 786-O cells.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carnea was isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 µmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins.

Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway.

The leading cause of cancer deaths is lung cancer, non-small cell lung cancer (NSCLC), the most common type of lung cancers, remains a difficult cancer to treat and cure. It is urgent to develop new products to treat NSCLS. Gracillin, extracted from Reineckia carnea, Dioscorea villosa, and other medicinal plants, has anti-tumor potential with toxic effect on a variety of tumor cells such as NSCLC. However, the anti-NSCLC mechanism of gracillin is not completely clear. In this study, A549 cells and athymic nude mice were used as models to evaluate the anti-NSCLC effects of gracillin. The antiproliferative activity of gracillin on A549 cells was conducted by CCK-8, and obvious autophagy was observed in gracillin-treated A549 through transmission electron microscopy. Furthermore, the expressions of Beclin-1, LC3-II, and WIPI1 were upregulated, while the expression of p62 was downregulated in gracillin-treated A549. The further mechanism study found that the mTOR signaling pathway was significantly inhibited by gracillin. Accordingly, the PI3K/Akt pathway positively regulating mTOR was inhibited, and AMPK negatively regulating mTOR was activated. Meanwhile, LC3-II transformation was found to be significantly reduced after WIPI1 was silenced in A549 cells but increased after gracillin treatment. It also proves that WIPI is involved in the process of gracillin regulating A549 autophagy. At last, the anti-tumor growth activity of gracillin in vivo was validated in A549-bearing athymic nude mice. In conclusion, gracillin has anti-NSCLC activity by inducing autophagy. The mechanism maybe that gracillin inhibited the mTOR signaling pathway. Gracillin has the potential to be a candidate product for the treatment of NSCLC in the future.

Gracillin Isolated from Reineckia carnea Induces Apoptosis of A549 Cells via the Mitochondrial Pathway.

BACKGROUND: Reineckia carnea is commonly used to treat cough, pneumonia and other diseases in China. In our previous study, it was found that the ethanol extracts of Reineckia carnea have a strong inhibitory effect on the proliferation of human lung cancer A549 cells. Here, we isolated gracillin from ethanol extracts for the first time. PURPOSE: Clarify the antiproliferation effect of gracillin on A549 cells and further explore its mechanisms via the mitochondrial pathway. METHODS: Gracillin was isolated and purified by silica gel, D-101 macroporous resin and preparative RP-HPLC, then identified by NMR and HR-MS. The inhibitory effects of gracillin on the proliferation of A549 cells were detected by the MTS method. Its mechanisms were further explored by flow cytometry and Western blot. RESULTS: A steroid saponin, gracillin, was isolated and identified from Reineckia carnea for the first time. In a concentration-dependent and time-dependent manner, gracillin significantly inhibited the proliferation of A549 cells with an IC50 value at 2.54 µmol/L and induced morphological changes. The results of flow cytometry analysis showed that the apoptosis rate of A549 cells was significantly increased (p < 0.05), and the cells proportion was obviously arrested in S phase. The concentration of intracellular calcium was raised (p < 0.01), and the mitochondrial membrane potential was greatly decreased (p < 0.01). In addition, the expression levels of Bax, caspase-3, cleaved caspase-3, and cytochrome C were dramatically up-regulated while Bcl-2 was down-regulated (p < 0.05) in A549 cells. CONCLUSION: This study confirmed that gracillin has a significant antiproliferative effect on A549 cells. Gracillin could induce the apoptosis of A549 cells through the mitochondrial pathway, which might be associated with regulation of the concentration of intracellular calcium, the mitochondrial membrane potential and the expression levels of Bax, Bcl-2, caspase-3, cleaved caspase-3, and cytochrome C.

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 Novel Fibrinolytic Protein From Pheretima vulgaris: Purification, Identification, Antithrombotic Evaluation, and Mechanisms Investigation.

Thrombotic diseases have been considered major causes of death around the world. Treatments with thrombolytic drugs, such as recombinant tissue-plasminogen activator, urokinase, and streptokinase, are reported to have a life-threatening bleeding tendency. On the contrary, lumbrokinase, identified from Lumbricus rubellus, is specific to fibrin and does not cause excessive bleeding. It possesses fibrinolytic activity and activation of plasminogen to dissolve fibrin. Hence, the purification of fibrinolytic protein monomer from earthworm and antithrombotic evaluation and investigation of mechanisms are needed. In this study, a novel fibrinolytic protein EPF3, with strong fibrinolytic activity, was purified from Pheretima vulgaris by ion exchange and size exclusion chromatography. SDS PAGE, bottom-up proteomics analysis, de novo sequencing, and circular dichroism (CD) analysis were carried out for identification and characterization of it. EPF3, with a molecular weight of 25136.24 Da, consisted of 241 amino acids and contained various forms of secondary structures, including α-helix (3.9%), ß-sheet (42.8%), ß-turn (21.2%), and random coil (32.1%). It was a trypsin-like serine protease and stable at pH 7.0 to 11.0 and below 40°C. EPF3 was confirmed to possess an antithrombotic effect by ex vivo clot lysis test and fibrinogen-thrombin time (Fib-TT) assay. The three-dimensional structure of EPF3 was predicted by SWISS-MODEL. Molecular docking analysis predicted that EPF3 could directly interact with antithrombotic target proteins (fibrin, fibrinogen, and plasminogen), which was further confirmed by further studies. The antithrombotic mechanism of EPF3 was clarified to be outstanding direct fibrinolysis, fibrinogenolytic activity, and certain activation of plasminogen. EPF3 possesses the potential to be developed into a promising antithrombotic agent.

Study on The Anti-Inflammatory Effects of Callicarpa nudiflora Based on The Spectrum-Effect Relationship.

Callicarpa nudiflora (C. nudiflora) is widely used to treat inflammation-related diseases in China. C. nudiflora mainly contains phenylethanol glycosides, flavonoids, triterpenes, diterpenes, iridoid glycosides, volatile oils, and other small molecules. Therefore, it is necessary to screen out anti-inflammatory active substances from C. nudiflora. In this paper, high-performance liquid chromatography was used to establish the fingerprint of C. nudiflora extracts. The anti-inflammation of C. nudiflora extracts were evaluated by the experiment of toes swelling in inflammatory rats. Then, the spectrum-effect relationship between the fingerprints and anti-inflammatory activities was researched by Pearson analysis and orthogonal partial least squares analysis to identify a group of anti-inflammatory compounds of C. nudiflora extracts. The differences of extracts are illustrated by principal component analysis and cluster analysis in pharmacological effects. Finally, 12 compounds, including catalpol (P1), caffeic acid (P2), protocatechuic acid (P9), 3,4-dihydroxybenzaldehyde (P10), forsythiaside E (P12), protocatechualdehyde isomers (P14), forsythiaside B (P15), rutin (P16), alyssonoside (P21), verbascoside (P22), 2'-acetyl forsythoside B (P24), and isorhamnetin (P32) by HPLC-DAD and UPLC-Q-TOF MS/MS, were determined as potential compounds for anti-inflammatory activity in C. nudiflora. In particular, six compounds were identified as active substances with the greatest anti-inflammatory potential. Moreover, all compounds were tested for anti-inflammatory experiments or anti-inflammatory literature retrieval. In this study, a method for rapid screening of potential anti-inflammatory active ingredients of C. nudiflora was established, which can provide a reference for the future study of active compounds of C. nudiflora.

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.

Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases.

Notoginsenoside (NG)-R1 is one of the main bioactive compounds from Panax notoginseng (PN) root, which is well known in the prescription for mediating the micro-circulatory hemostasis in human. In this article, we mainly discuss NG-R1 in metabolism and the biological activities, including cardiovascular protection, neuro-protection, anti-diabetes, liver protection, gastrointestinal protection, lung protection, bone metabolism regulation, renal protection, and anti-cancer. The metabolites produced by deglycosylation of NG-R1 exhibit higher permeability and bioavailability. It has been extensively verified that NG-R1 may ameliorate ischemia-reperfusion (IR)-induced injury in cardiovascular and neuronal systems mainly by upregulating the activity of estrogen receptor α-dependent phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor erythroid-2-related factor 2 (NRF2) pathways and downregulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. However, no specific targets for NG-R1 have been identified. Expectedly, NG-R1 has been used as a main bioactive compound in many Traditional Chinese Medicines clinically, such as Xuesaitong, Naodesheng, XueShuanTong, ShenMai, and QSYQ. These suggest that NG-R1 exhibits a significant potency in drug development.

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.