ABSTRACT
Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro , but the EC content decreased on the 7 th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.
Subject(s)
Collagen , Drug Combinations , Fibroblasts , Laminin , Penis , Proteoglycans , Tissue Engineering , Tissue Scaffolds , Humans , Male , Tissue Engineering/methods , Myocytes, Smooth Muscle , Endothelial Cells , Cells, Cultured , Cell DifferentiationABSTRACT
Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.
Subject(s)
Boron , Fluorescent Dyes , Methanol , Glycerol , Lipopolysaccharides , Nystatin , Lysosomes , Benzothiazoles , Acetonitriles , Solvents , Autophagy , Water , DexamethasoneABSTRACT
In the era of artificial intelligence based on big data, data acquisition, storage and processing are more convenient, which provides a guarantee for accelerating the development of traditional Chinese medicine (TCM), but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM, combined with the current development trend of artificial intelligence, this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template", in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template", the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM, in which the self-recognition, self-assembly, self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes:the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM, and store the memory information database in the meridian and collateral organs in the form of "imprinting template", and then pass the "imprinting template". The comparison, analysis, and judgment of imprinting templates guide the self-assembly, self-organization and self-replication among "molecular society", synthesize biological machines, produce biological functions, repair or strengthen biological supramolecular bodies, and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence", while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world, artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world, suggesting the development direction of "intelligence" functionalization of drug innovation mode.
ABSTRACT
Hydrogen peroxide (H2O2) plays vital roles in oxidative stress and signal transduction in living organisms, and its abnormal levels could be linked to many diseases. Despite numerous efforts spent, it is still urgent and of high importance to develop better H2O2 probes with good selectivity, high sensitivity and low backgrounds. To this end, a novel boron dipyrromethene (BODIPY)-based fluorescent probe with an electron-withdrawing methylenemalononitrile at the meso position has been rationally designed, successfully synthesized and investigated for detection of H2O2 in aqueous solutions and living cells, which exhibited high selectivity and sensitivity, fluorescent "turn-on" phenomenon at 540 nm, and ratiometric changes from 506 to 540 nm. Upon exposure to H2O2, a strong fluorescent emission at 540 nm appeared and the corresponding quantum yields changed from 0.009 to 0.13. The detection limit towards H2O2 was calculated to be 31 nM by the linear fluorescence change at 540 nm in the H2O2-concentration ranging from 2 to 10 µM. This probe was applicable in a pH range from 6 to 10. Meanwhile, the sensing mechanism was also confirmed by the 1H NMR and mass spectrometry, suggesting that the above changes might be ascribed to the quick addition and oxidization of the double bond. Furthermore, confocal imaging results also showed great enhancement of intracellular fluorescence upon exposure to H2O2 and PMA in RAW264.7 cells, unambiguously confirming its great potentials as a fluorescent probe for highly sensitive detection of both exogenous and endogenous H2O2 in living cells.
Subject(s)
Boron Compounds/chemistry , Fluorescent Dyes/chemistry , Hydrogen Peroxide/analysis , Nitriles/chemistry , Optical Imaging , Animals , Dose-Response Relationship, Drug , Fluorescent Dyes/chemical synthesis , HEK293 Cells , Humans , Mice , Molecular Structure , RAW 264.7 Cells , Structure-Activity RelationshipABSTRACT
A series of 1,2,4-triazole-norfloxacin hybrids was designed, synthesized, and evaluated for in vitro antibacterial activity against common pathogens. All the newly synthesized compounds were characterized by Fourier-transform infrared spectrophotometry, proton and carbon nuclear magnetic resonance, and electrospray ionization-mass spectrometry. Representative compounds from each step of the synthesis were further characterized by X-ray crystallography. Many of the compounds synthesized exhibited antibacterial activity superior to that of norfloxacin toward both, gram-positive and gram-negative bacteria. The toxicity of the 1,2,4-triazole-norfloxacin hybrids toward bacterial cells was 32-512 times higher than that toward mouse fibroblast cells. Moreover, hemolysis was not observed at concentrations of 64 µg/mL, suggesting good biocompatibility. Molecular docking showed a least binding energy of -9.4 to -9.7 kcal/mol, and all compounds were predicted to show remarkable affinity for the bacterial topoisomerase IV.
Subject(s)
Anti-Bacterial Agents/pharmacology , Dose-Response Relationship, Drug , Molecular Docking Simulation , Norfloxacin/pharmacology , Triazoles/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Crystallography, X-Ray , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Norfloxacin/chemical synthesis , Norfloxacin/chemistry , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
Severe acute respiratory syndrome coronavirus 2-infected pneumonia (novel coronavirus-infected pneumonia [NCIP]) is a new viral illness initially identified in the central Chinese city of Wuhan in December 2019. According to the daily report on the epidemic situation of coronavirus disease (COVID-19) issued by the National Health and Family Planning Commission of the People's Republic of China on March 23, 2020: COVID-19 is highly infectious, causing extremely high incidence of NCIP throughout Wuhan and has spread swiftly to 34 provinces within China and >100 other countries around the world between January and March 2020. Up to August 11, 2020, there have been 89,383 cases diagnosed as coronavirus-infected pneumonia; and 4,696 deaths in China (mortality rate of 5.25%) and worldwide reports have confirmed 19,936,210 cases and 732,499 deaths. These figures have been increasing daily. The treatment of viral conditions is well established within the context of Chinese Medicine. We report 2 successful cases in this study showing the patient's chest computed tomography scans and temperature charts made on before, during, and after treatment to demonstrate proof of the positive benefits achieved. Traditional Chinese Medicine (TCM) demonstrates a positive effect in the treatment for COVID-19. It is highly recommended that TCM be incorporated early on in the treatment schedule for COVID-19.
ABSTRACT
The application of modern scientific theories and technologies to explore the mechanism of Chinese medicine and its compounds is one of the key issues in realizing the modernization of traditional Chinese medicine (TCM) research. Chinese medicine and its compounds produce comprehensive pharmacodynamics through multiple components acting on multiple targets, the core of clarifying the mechanism is to solve the key scientific problems of static correlation and dynamic integration verification between the components and the target network topology. At present, the effective method to clarify the mechanism of Chinese medicine and its compounds is to statically correlate the topological network of in vitro components and targets through network pharmacology. Although there are also component-target verification studies, they often learn from research idea of single component-single target, it is urgent to establish a quantitative integration and overall verification method that conforms to the characteristics of TCM. According to supramolecular Qi chromatography theory of TCM, the microscopic mechanism of interaction between Chinese medicine and human body is actually the two supramolecular host and object groups (the active ingredient group of Chinese medicine and the target group of human body) based on imprinted template, which shows the macroscopic properties and pharmacodynamics. Based on this, the author proposes to use supramolecular Qi chromatography theory as the guidance, combined with supramolecular chemistry, network dynamics, quantitative pharmacology and other methods to quantitatively integrate and verify the compositions and the target groups with imprinted template as the core predicted by network pharmacology, looking for the optimal quality markers, greatly reducing the difficulty of multi-component-multi-target experimental verification of Chinese medicine and its compounds.
ABSTRACT
Objective:To construct the targeting evaluation method of traditional Chinese medicine (TCM) preparations based on supramolecular Qi chromatography theory, and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index (MCI) was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang, and combined with target dynamics and total statistical moment principle, aimed at the independent action characteristics of multi-component imprinted template of TCM, a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group, Bupleuri Radix<italic> </italic>group, Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted, the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8, Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2, so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established, including relative total uptake efficiency (RUE<sub>T</sub>), relative total concentration (RC<sub>T</sub>), relative imprinted tendency (RIT<sub>T</sub>) and relative imprinted variance (RIV<sub>T</sub>). The RUE<sub>T</sub> and RC<sub>T</sub> of liver were the highest in all tissues (RUE<sub>T</sub>=1.88>1,RC<sub>T</sub><italic>=</italic>2.30>1), and the corresponding values of other tissues were all <1, indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma, the RIT<sub>T</sub> and RIV<sub>T</sub> of other tissues fluctuated around 1.0, indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory, a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters, so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.
ABSTRACT
Three aroylhydrazone ligands ((Z)-N'-([2,2'-bithiophen]-5-ylmethylene)-2-hydroxybenzohydrazide, HL1; (Z)-N'-([2,2'-bithiophen]-5-ylmethylene)-3-hydroxybenzohydrazide, HL2; and (Z)-N'-([2,2'-bithiophen]-5-ylmethylene)-4-hydroxybenzohydrazide, HL3) and their complexes with nickel (Ni(L1)2, 1; Ni(L2)2, 2; Ni(L3)2âDMF, 3) were synthesized and characterized by ESI-MS, NMR, IR, UV-vis and elemental analysis techniques. The molecular structure of ligand (HL2) and complexes 1-3 was confirmed by single crystal X-ray crystallography. The single crystal X-ray structure of complexes 1-3 showed a distorted square planar geometry around the metal center, and the ligands adopt a bidentate chelating mode. The interaction of calf thymus (ctDNA) with nickel(II) complexes was explored using absorption, emission spectrum, viscosity, and circular dichroism methods. These complexes exhibited moderate affinity for ctDNA through groove binding modes. The most efficient DNA binder was complex 2. The interaction of the complexes with DNA has also been supported by molecular docking study and molecular dynamics simulation. An in vitro cytotoxicity study of the complexes found low activity against human cervical (Hela) and breast (MCF-7) cancer cell lines, with the best results for complex 2, where IC50 values are 86 µM and 92 µM respectively.
Subject(s)
Coordination Complexes/chemistry , Hydrazones/chemistry , Nickel/chemistry , Animals , Cattle , Cell Line, Tumor , DNA/chemistry , Humans , Molecular Structure , Spectrum Analysis/methodsABSTRACT
In this work, three aroylhydrazone ligands ((E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL1; (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL2; and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL3) and their complexes with nickel (Ni(L1)2, NiL1; Ni(L2)2â2DMF, NiL2; Ni(L3)2â2DMF, NiL3) were prepared. The single crystal X-ray structures analysis of three compounds showed that they were neutral. The ligand adopts tridentate chelating mode. The nickel ion is six-coordinate with two O atoms and four N atoms from two ligands, and forms an octahedral arrangement. The investigation of DNA binding ability by ultraviolet and fluorescence titrations showed that NiL2 and NiL3 exhibit moderate binding affinity toward calf Thymus DNA. Spectroscopy, molecular docking, and molecular dynamics simulation indicated that NiL2 and NiL3 bind at the minor groove of DNA through intercalation.
Subject(s)
Coordination Complexes/chemical synthesis , Hydrazones/chemistry , Intercalating Agents/chemical synthesis , Nickel/chemistry , Organometallic Compounds/chemical synthesis , DNA/chemistryABSTRACT
Three novel copper(ii) complexes, Cu(L1)2 (1), Cu(L2)2·2DMF (2), and Cu(L3)2·2DMF (3), were synthesized using three aroylhydrazone ligands, (E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL1), (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2) and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL3). The complexes were characterized by elemental analysis, infrared (IR), and Ultraviolet-visible light (UV-vis) spectroscopy. The X-ray crystal structures of the complexes all possess a distorted octahedral coordination geometry. Both an absorption spectral titration and a competitive binding assay (ethidium bromide, 4',6-diamidino-2-phenylindole (DAPI), and methyl green) revealed that complexes 2 and 3 bind readily to calf thymus DNA (ctDNA) through intercalative and minor groove binding modes. Complexes 2 and 3 also exhibited oxidative cleavage of supercoiled plasmid DNA (pUC19) in the presence of ascorbic acid as an activator. Cytotoxicity studies showed that complexes 2 and 3 possessed high cytotoxicities toward the HeLa human cervical cancer cell line, but weak toxicities toward the L929 normal mouse fibroblast cell line. We therefore have reason to believe that complexes 2 and 3 both show potential as promising anticancer candidate drugs.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Copper/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Animals , Cell Line , Cell Survival/drug effects , DNA Cleavage , Humans , Ligands , Mice , Models, Molecular , Molecular StructureABSTRACT
Research has revealed that microRNA (miR)4500 is downregulated in nonsmall cell lung cancer (NSCLC), and miR4500 suppresses tumor growth by targeting lin28 homolog B and NRAS protooncogene, GTPase. In the present study, it was reported that signal transducer and activator of transcription 3 (STAT3) may function as a novel target gene for miR4500 in NSCLC. The experiments conducted in the present study confirmed that the miR4500 expression was decreased in NSCLC tissues and cells compared with adjacent normal tissues and a normal lung cell line. miR4500 suppressed the cell proliferation, migration, invasion and promoted apoptosis of the human NSCLC cell lines A549 and H1975. Expression of STAT3 was negatively correlated with miR4500 expression in vivo. A luciferase reporter assay suggested that miR4500 directly targeted the 3' untranslated region of STAT3. The tumor inhibition effect of small interfering RNA STAT3 in A549 and H1975 lines may be partially impaired by a miR4500 inhibitor. The results of the present study suggests that miR4500 may be a tumor suppressor and a potential therapeutic target in NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , MicroRNAs/genetics , STAT3 Transcription Factor/genetics , 3' Untranslated Regions , A549 Cells , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation , Disease Progression , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathologyABSTRACT
In the present study, the expression of microRNA (miR)6713p in nonsmallcell lung cancer (NSCLC) was detected via reverse transcriptionquantitative polymerase chain reaction analysis, and its role in cell proliferation, apoptosis, migration and invasion was investigated via Cell Counting Kit8, colony formation, flow cytometry, Transwell and scratch assays, respectively. It was observed that the expression of miR6713p was upregulated in NSCLC tissues and cell lines (A549 and H1975). Treatment with miR6713p inhibitors suppressed cell proliferation, migration and invasion, and increased apoptosis in vitro, suggesting that miR6713p functions as an oncogene in NSCLC. In addition, forkhead box P2 (FOXP2) has been reported to be a tumor suppressor that is downregulated in several types of cancer, and its low expression was confirmed in NSCLC tissues and cell lines in the current study via western blotting. The results of the luciferase reporter assay also demonstrated that miR6713p targeted directly the 3'untranslated region of FOXP2. Furthermore, overexpression of FOXP2 in A549 and H1975 cell lines suppressed the growth, migration and invasion, and promoted apoptosis, whereas these effects were reversed by transfection with miR6713p mimics, suggesting that miR6713p promoted tumor progression via regulating FOXP2. Taken together, the results reported in the present study implied that miR6713p may be a potential therapeutic target in NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Forkhead Transcription Factors/biosynthesis , Gene Expression Regulation, Neoplastic , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/biosynthesis , RNA, Neoplasm/metabolism , A549 Cells , Aged , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Female , Forkhead Transcription Factors/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Proteins/genetics , RNA, Neoplasm/geneticsABSTRACT
This study aimed to evaluate the prognosis of pulmonary sequestration (PS) by measuring congenital cystic adenomatoid malformation volume ratio (CVR) value in fetal congenital PS. The fetal CVR in 49 cases of fetal PS diagnosed by prenatal ultrasound in Xiangyang No. 1 People's Hospital from March 2010 to June 2017 were measured, and the clinical outcomes were observed. According to the prenatal ultrasound CVR value, 49 fetuses diagnosed with PS were divided into 2 groups: group 1 with CVR≥1.26, and group 2 with CVR<1.26. The incidence rate of fetal edema, respiratory distress symptoms and survival rate were compared between the two groups. The risk factors of the fetal PS were evaluated by single and multiple Logistic regression analysis. The correlation between CVR and fetal prognosis was analyzed. Of the 49 fetuses, there were 34 cases of PS (ILS) type (69.39%, 34/49), 10 cases of PS (ELS) type I (20.41%, 10/49) and 5 cases of PS (ELS) type II (10.20%, 5/49). Forty-six cases (93.88%, 46/49) were born alive, there was 1 case (CVR ≥1.26) (2.04%, 1/49) of induced abortion, and 2 cases (CVR ≥1.26) (4.08%, 2/49) of stillbirths. In group 1 (n=24), 21 cases were born alive, and the incidence rate of newborn respiratory distress and fetal edema was 100% (21/21) and 79.17% (19/24) respectively. In group 2 (n=25), there were 3 cases (12%,3/25) of newborn respiratory distress, 3 cases (12%, 3/25) of fetal edema, and the rate of live birth was 100%. There were statistically significant differences between the two groups in the incidence of fetal edema, postpartum respiratory symptoms and survival rate. CVR was a risk factor for PS and was associated with fetal prognosis. CVR in the midtrimester of pregnancy is an effective index to evaluate the prognosis of fetal PS. CVR ≥1.26 is associated with an increased risk of fetal edema, infant respiratory distress and intrauterine or postnatal death.
Subject(s)
Bronchopulmonary Sequestration/diagnosis , Cystic Adenomatoid Malformation of Lung, Congenital/diagnostic imaging , Fetus/diagnostic imaging , Lung/diagnostic imaging , Bronchopulmonary Sequestration/diagnostic imaging , Bronchopulmonary Sequestration/pathology , Cystic Adenomatoid Malformation of Lung, Congenital/physiopathology , Female , Fetus/physiopathology , Humans , Infant, Newborn , Live Birth , Lung/physiopathology , Pregnancy , Prognosis , Treatment OutcomeABSTRACT
Stroke has caused a heavy disease burden across the world, and it has become a worldwide public health problem. Several studies have assessed the relationship between psychological and social factors and risk of stroke so far. This paper summarizes the progress in epidemiological research on the relationship between psychological and social factors (depression, psycho-social stress, anxiety, loneliness, psychological distress, social support, social isolation, and social network) and the risk for stroke, the results of these studies were inconsistent. Most studies showed an association between these factors and the incidence of stroke, but there were still some studies showing no such association.
ABSTRACT
This paper discussed the use of glucocorticoids in amniotic fluid embolism treatment by analyzing the pathophysiological basis of amniotic fluid embolism and the pharmacological effects of glucocorticoids,and expounded the viewpoints and controversial issues supporting the application of glucocorticoids in amniotic fluid embolism.The conclusion is that there is no evidence to support the conventional use of glucocorticoids in the treatment of amniotic fluid embolism,although there is theoretical basis.It is controversial to use or not use large doses of glucocorticoids.
ABSTRACT
BACKGROUND: Nonmuscle-invasive bladder cancer (NMIBC, Stage T1 or lower) is treated with transurethral resection (TUR), while muscle-invasive bladder cancer (MIBC, Stage T2 or more) requires neoadjuvant chemotherapy before radical cystectomy. Hence, preoperative differentiation is vital. PURPOSE: To investigate whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can differentiate NMIBC from MIBC and to assess whether there were correlations between IVIM parameters and the Ki-67 labeling index (LI). STUDY TYPE: Retrospective. SUBJECTS: Thirty-six patients diagnosed with bladder cancer confirmed by histopathological findings. FIELD STRENGTH/SEQUENCE: 3.0T magnetic resonance imaging (MRI) DWI with eight b-values ranging from 0 to 1000 s/mm2 . ASSESSMENT: Molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were calculated by biexponential and monoexponential models fits, respectively. STATISTICAL TESTS: Comparisons were made between the MIBC and NMIBC group, and differences were analyzed by comparing the areas under the receiver-operating characteristic curves (AUCs). The correlations between these parameters and Ki-67 LI were assessed by Spearman's rank correlation analysis. RESULTS: The ADC and D value were significantly lower in patients with MIBC compared to those with NMIBC (P < 0.01). No significant (P > 0.05) differences were observed in D* and f. The AUC of D value (0.894) was significantly (P < 0.05) larger than the ADC value (0.786), with sensitivities and specificities of 95% and 87.5% (D) and 80% and 68.7% (ADC), respectively. In addition, the D and ADC values were significantly correlated with Ki-67 LI (r = -0.785, r = -0.643, respectively; both P < 0.01). DATA CONCLUSION: The D value obtained from IVIM exhibited better performance than conventional DWI for distinguishing NMIBC from MIBC and may serve as a potential imaging biomarker for bladder cancer invasion. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1054-1060.
Subject(s)
Cell Proliferation , Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness/diagnostic imaging , Neoplasm Invasiveness/pathology , Phosphoproteins , Reproducibility of Results , Sensitivity and Specificity , Urinary Bladder/diagnostic imaging , Urinary Bladder/pathologyABSTRACT
BACKGROUND: The bladder wall may thicken resulting from chronic inflammation after initial treatment (transurethral resection [TUR] or neoadjuvant chemotherapy), which may mimic the feature of recurrent or residual bladder tumors (RBT). Therefore, it is critical to discriminate RBT from benign lesions after initial treatment. PURPOSE: To investigate whether diffusion kurtosis imaging (DKI) could discriminate RBT from post-therapy bladder inflammatory lesions. STUDY TYPE: Retrospective. SUBJECTS: Fifty patients diagnosed with bladder cancer underwent TUR or received neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0T MRI/conventional T1 -weighted imaging (T1 WI), T2 WI, and diffusion-weighted imaging (DWI) with nine b-values ranging from 0-2000 s/mm2 . ASSESSMENT: Mean diffusion coefficients (MDa , MDb , and MDc ) and mean kurtosis values (MKa , MKb , and MKc ) were obtained from three different measurement methods. The region of interest (ROI) was placed 1) to encompass the entire portion of the thickening bladder wall or to portions that were the most restricted, with a b-value of 2) 2000 s/mm2 or 3) 1000 s/mm2 . STATISTICAL TESTS: The independent-samples t-test was used to compare the differences between RBT and the inflammatory group. Differences in DKI parameters were analyzed by comparing the areas under the receiver-operator characteristic curves (AUCs). RESULTS: In patients with RBT, the MD (MDa , MDb , MDc ) values were significantly lower and the MK (MKa , MKb , MKc ) values were significantly higher than those in patients in the inflammatory lesions group (all P < 0.01). The AUC of MKb (0.934) was significantly larger than those of MDb , MKa , and MKc (0.793, P < 0.05; 0.694, P < 0.01; 0.719, P < 0.01, respectively). DATA CONCLUSION: MK obtained from DKI provided better performance than conventional DWI in distinguishing RBT from inflammatory lesions after bladder cancer treatment. MK calculated with high b-values setting provided better performance in differentiation. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2017.
Subject(s)
Diffusion Magnetic Resonance Imaging , Inflammation/diagnostic imaging , Urinary Bladder Neoplasms/diagnostic imaging , Aged , Area Under Curve , Chemotherapy, Adjuvant , Diffusion Tensor Imaging , Female , Humans , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Male , Middle Aged , Neoadjuvant Therapy , Normal Distribution , ROC Curve , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Objective To investigate the frailty status and related determinants among the elderly in China.Methods Frailty index (FI) was applied to evaluate the frailty status of the elderly.Data used in this study was from the China Health and Retirement Longitudinal Study (CHARLS) in 2011-2015.Binary logistic regression analysis was carried out to identify the determinants related to the status on frailty.Results The prevalence rates of frailty in the elderly were 18.7%,20.6% and 28.4% in 2011,2013 and 2015,respectively.Being female or elderly under advanced age,were both associated with the higher level of FI.Factors as hip fracture,falls,alcohol intake more than once a month,and less participation in social activities etc.,might serve as the risk factors for frailty.Conclusion Chinese elderly showed relatively high prevalence on frailty and with annual increasing trend.The status of frailty was related to factors as adverse events and unhealthy lifestyles.Comprehensive intervention strategies should be adopted in early life of the elderly to delay the development process of frailty.
ABSTRACT
Both the increasing prevalence and growing burden of diabetes mellitus have caused global public health concerns.With the development of bio-psycho-social medical model,the impact of psychosocial factors on diabetes has attracted more attentions among the researchers.This paper summarizes findings from epidemiological studies that focusing on the association between diabetes and related psychosocial risk factors.Foreign studies have shown that psychological factors are closely related to diabetes,but the conclusions on social factors are inconsistent.Domestic studies have only targeted on small-sample-sized and cross-sectional studies.More longitudinal research is needed to confirm the impact of psychosocial factors on the risk of diabetes.