Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies / 中草药·英文版

OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Study on the stability and H+ permeable membrane properties of polymersomes / 药学实践杂志

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

Effects of the application of sodium ascorbate after in-office bleaching on the penetration of hydrogen peroxide, color change, and microtensile bond strength

Abstract This study aimed to evaluate the effects of the application of 10% sodium ascorbate (SA) after in-office bleaching on the penetration of hydrogen peroxide (HP) into the pulp chamber, color change, and microtensile bond strength (µTBS) to the resin-enamel interface. Thirty premolars and thirty molars were randomly divided into three groups (n = 20 each). One group was exposed to deionized water (negative control). The other two groups were bleached with 35% HP in a single session for 3x15 minutes for each application. However, in only one of them, SA was applied for 10 minutes after bleaching. After, the concentration (µg/mL) of HP in each pulp chamber was evaluated by UV-Vis spectrophotometry. Color changes (ΔEab, ΔE00, and ΔWID) were evaluated with a digital spectrophotometer before and in the first week after bleaching. After treatment, molars were restored and sectioned to obtain resin-enamel interface sticks for µTBS at a crosshead speed of 1 mm/min until failure. The HP concentration and µTBS data were analyzed using one-way ANOVA and Tukey tests, and color changes were analyzed by t-tests (α = 0.05). SA application significantly improved the µTBS values and reduced the HP concentrations within the pulp chambers (p < 0.0001). The application of SA significantly interfered with the color changes after bleaching when compared to the control group (p < 0.05). Application of 10% SA after in-office bleaching successfully reduced the penetration of HP into the pulp chamber; however, it decreased color change.

Resumo Este estudo teve como objetivo avaliar os efeitos da aplicação do ascorbato de sódio a 10% (AS) depois do clareamento em consultório na penetração do peróxido do hidrogênio (PH) na câmara pulpar, mudança de cor e resistência de união (RU) da interface resina-esmalte. Trinta pré-molares e trinta molares foram divididos aleatoriamente em três grupos (n = 20). Um grupo foi exposto em água deionizada (controle negativo). Os outros dois grupos foram clareados com 35% PH numa única sessão de 3x15 minutos para cada aplicação. Porém, só um grupo recebeu AS durante 10 minutos depois do clareamento. Depois, a concentração (µg/mL) do PH no interior de cada câmara pulpar foi avaliado com espectrofotometria UV-Vis. A mudança de cor (ΔEab, ΔE00 and ΔWID) foi avaliada como espectrofotômetro digital antes e depois de uma semana do clareamento. Após de cada tratamento, os molares foram restaurados e seccionados em espécimes com interface resina-esmalte para o teste de RU por microtração a uma velocidade de 1 mm/min até a fratura. Os dados da concentração de PH e RU foram analisados usando ANOVA de uma via e teste de Tukey, e a mudança de cor com o teste t (α = 0.05). A aplicação de AS melhorou significativamente a RU e reduziu a concentração de PH na câmara pulpar (p < 0.0001). A aplicação de AS interferiu significativamente na mudança de cor depois do clareamento comprado com o grupo controle (p < 0.05). A aplicação de SA a 10% depois do clareamento em consultório reduziu significativamente a penetração do PH na câmara pulpar e interferiu na mudança de cor.

Análisis bidimensional de la permeabilidad de vías aéreas con el tamaño de senos maxilares y su relación con el desarrollo de la clase esqueletal en una población mexicana / Two-dimensional analysis of airway permeability with maxillary sinus size and its relationship with the development of skeletal class in a Mexican population

Comparar la permeabilidad de las vías aéreas y el tamaño de los senos maxilares en relación con la clase esqueletal. se midieron 90 radiografías lateral de cráneo, divididas en 3 grupos, comparando las 3 clases esqueletales, las cuales se determinaron con la medida ANB de Steiner, y estas a su vez en dos subgrupos que fueron hombres y mujeres, en las cuales se utilizó el análisis de McNamara para el análisis de vías aéreas y para el área del seno maxilar se tomaron dos medidas una antero-posterior y cefálica-caudal. Al comparar los hombres con las mujeres se identificó significancia estadística en vía área superior de clase II (p=≤0.017), vía aérea inferior de clase III (p=≤0.006). Al comparar las clases esqueletales en hombres se identificó diferencias en la vía aérea superior en las clases I vs III (p=≤0.05), inferior en la clase I vs III (p=≤0,001) y II vs III (p=≤0.044). Con respecto a mujeres se identificó significancia en la vía aérea superior al comparar la clase I vs II (p=≤0,043), vía aérea inferior en la clase II vs III (p=≤0.05), longitud del seno maxilar al comparar clase I vs II (p=≤0.017). Entre la clase I esqueletal y la clase II, el tamaño de los senos maxilares resulto menor en longitud en las mujeres de clase II esqueletal. Entre la clase I y clase III esqueletal en hombres, se encontró una longitud menor en la vía aérea superior e inferior en la clase I. Las vías aéreas resultaron en menor tamaño en sujetos de clase II.

SUMMARY: To compare the airway permeability and the size of the maxillary sinuses in relation to the skeletal class. 90 lateral skull radiographs were divided into 3 groups, comparing the 3 skeletal classes, which were determined with Steiner's ANB measurement, and these were once in two subgroups that were men and women, in any McNamara analysis was used for the analysis of airways and for the maxillary sinus area measurements were made an antero-posterior and cephalic-caudal. When comparing males with females, statistical significance was identified in the upper class II route (p=≤0,017), lower class III airway (p=≤0.006). At least skeletal classes in men, differences were identified in the upper airway in classes I vs III (p=≤0.05), lower in class I vs III (p=≤0.001) and II vs III (p=≤0.044). With respect to women, significance was identified in the upper airway when comparing class I vs II (p=≤0.043), lower airway in class II vs. III (p=≤0.05), maxillary sinus length to class I vs II (p=≤0.017). Between skeletal class I and class II, maxillary sinus size was shorter in length in skeletal class II women. Between class I and skeletal class III in men, a lower length was found in the upper and lower airways in class I. The airways were found to be smaller in class II subjects.

Research Progress on Capillary Leak Syndrome Associated with Hematopoietic Stem Cell Transplantation--Review / 中国实验血液学杂志

Capillary leak syndrome (CLS) is a clinical syndrome characterized by impairment of vascular endothelial barrier function, increased vascular permeability, and reversible systemic edema. It is one of the early fatal complications after hematopoietic stem cell transplantation. So far, the exact pathogenesis of CLS has not been elucidated, and the diagnostic criteria and treatment methods have not been unified. At present, it is believed that the fundamental cause of CLS is hypercytokinemia, and the core factor is high permeability of vascular endothelial cells. According to the clinical manifestations, the natural course of CLS can be divided into prodrome, leakage and recovery stages. As far as treatment is concerned, symptomatic and supportive treatment is dominant according to different characteristics of each stage. In this review, the pathogenesis, clinical manifestations, diagnosis and treatment of hematopoietic stem cell transplant-associated CLS were briefly summarized.

Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds / 生物医学工程学杂志

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism / 中国中药杂志

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

Application and problems analysis of traditional Chinese medicine volatile oil preparation technology based on ionic liquids / 中国中药杂志

Ionic liquids(ILs) are salts composed entirely of anions and cations in a liquid state at or near room temperature, which have a variety of good physicochemical properties such as low volatility and high stability. This paper mainly reviewed the research overview of ILs in the application of traditional Chinese medicine(TCM) volatile oil preparation technology. Firstly, it briefly introduced the application of TCM volatile oil preparation technology and composition classification and physicochemical properties of ILs, and then summarized the application of ILs in the extraction, separation, analysis, and preparation of TCM volatile oil. Finally, the problems and challenges of ILs in the application of TCM volatile oil were explained, and the application of ILs in TCM volatile oil in the future was prospected.

Clinicopathological features analysis of focal segmental glomerulosclerosis after kidney transplantation / 器官移植

Objective To investigate the clinicopathological features of recurrent and de novo focal segmental glomerulosclerosis (FSGS) after kidney transplantation. Methods Thirty-four recipients pathologically diagnosed with FSGS by renal allograft biopsy were enrolled in this clinical trial. According to the detection of primary diseases of renal allografts and circulating permeability factors, 34 recipients were divided into the recurrent FSGS group (n=12) and de novo FSGS group (n=22). The differences of clinical indexes and the degree of pathological injury of renal allografts were compared between two groups. Results There was no significant difference in the mesangial hyperplasia score, glomerulosclerosis rate, renal tubular atrophy score, interstitial fibrosis score and podocyte proliferation rate between two groups (all P > 0.05). In the recurrent FSGS group, segmental glomerulosclerosis rate of the recipients was 0.10 (0.08, 0.27), lower than 0.19 (0.13, 0.33) in the de novo FSGS group (P < 0.05). No significant difference was found in the incidence of antibody-mediated rejection, drug-induced renal tubular injury and BK virus infection between two groups (all P > 0.05). The incidence of T cell-mediated rejection in the recurrent FSGS group was 17%, lower than 55% in the de novo FSGS group (P < 0.05). Immunohistochemical staining showed that the infiltrating inflammatory cells in the renal allografts were mainly T lymphocytes. The positive rates of C4d deposition in peripheral capillaries between the recurrent and de novo FSGS groups were 33% (4/12) and 32% (7/22), with no significant difference (P > 0.05). Immunofluorescence results revealed IgM deposition in the segmental glomerulosclerosis area of renal allografts in most cases. Electron microscopy showed extensive fusion or segmental distribution of podocytes in the glomerulus of renal allografts. Conclusions The degree of renal functional injury and the incidence of T cell-mediated rejection in the recurrent FSGS group are lower than those in the de novo FSGS group. Comprehensive analysis of preoperative and postoperative clinical manifestations, laboratory testing and pathological examination of kidney transplant recipients contribute to early diagnosis and treatment of recurrent and de novo FSGS.

Exploring the ability of TAT, a cell-penetrating peptide, to deliver proteins in a non-fused form / 药学学报

Accumulating evidence has shown that the cell-penetrating peptide TAT can be applied to deliver different types of drug molecules, including nucleic acids, proteins and small molecule drugs. Usually TAT delivers cargoes on the basis of their covalent bonds or non-covalent interactions. However, there are few reports on the delivery of proteins by TAT in a non-covalent manner, and no quantitative comparisons have been made on the protein delivery ability of TAT in fusion and non-fusion manners. In order to explore the ability of TAT to deliver proteins in non-fusion manner, here we used fluorescence microscopy and flow cytometry to investigate the ability of TAT to deliver enhanced green fluorescent protein (EGFP) into non-small cell lung cancer cells A549 in a non-fusion manner. It was found that TAT could deliver EGFP into A549 cells, and its delivery ability was positively correlated with its concentration. In addition, the fusion protein TAT-EGFP was overexpressed and purified, and its permeability across cell membrane was also investigated. In this paper, based on quantitative comparison, we found that the delivery of EGFP by TAT in fusion manner is significantly efficient than that of TAT in non-fusion manner. This is the report that TAT can deliver EGFP in a non-fusion manner. Although its delivery efficiency remains to be improved as compared with the fusion manner, the non-fusion manner has shown incomparable advantages in ease of operation, suggesting that it is also a candidate for delivery strategy in the future.

Effects of heat stress on intestinal tract and cognitive function / 环境与职业医学

Heat stress refers to a series of stress reactions such as heat balance disturbance and physiological dysfunction when the body is exposed to the thermal environment for a long time. Studies have found that heat stress can damage intestinal morphology, such as length of intestinal villi, number of goblet cells, and depth of the crypt, affecting the digestion and absorption functions. It also can increase the permeability of the intestinal barrier by damaging the tight junction of the intestinal epithelium, which in turn allows endotoxin and bacteria to enter the blood circulation from the intestinal cavity to cause a systemic inflammatory response. At the same time, heat stress can disrupt the homeostasis of intestinal microbiota, increase pathogenic bacteria, and change downstream metabolites such as short-chain fatty acids. In addition, heat stress can inhibit the occurrence of hippocampal neurons and reduce the number of neurons; decrease the density of synapses; damage important organelles of neurons; induce inflammation of the central nervous system, and then lead to cognitive dysfunction. The brain-gut axis is a two-way signal axis between the intestine and the brain. Intestinal microorganisms and the intestinal barrier can participate in central nervous system regulation, and the brain can change the intestinal homeostatic function and affect the quality of the intestinal barrier through the hypothalamic-pituitary-adrenal axis (HPA axis). The interaction plays an essential role in the body's homeostasis. Therefore, this article reviewed current understandings on the impacts of heat stress on the gut and cognitive function, aiming to provide a reference for subsequent research.

Intervention Mechanism of Huangqintang on Intestinal Inflammation and Proliferation in Colitis-associated Colon Cancer / 中国实验方剂学杂志

ObjectiveTo investigate the efficacy of Huangqintang on mouse models of colitis-associated colon cancer （CAC） and explore the mechanism of Huangqintang in regulating immune function and inflammatory response， inhibiting abnormal cell proliferation， and delaying or inhibiting CAC formation in CAC. MethodC57BL/6J mice were randomly divided into a normal group， model group， mesalazine group， and high- and low-dose Huangqintang groups according to body weight， with 12 mice in each group. Except for the normal group， the rest of the mice were given two intraperitoneal injections of 10 mg·kg-1 azomethane （AOM） and allowed to drink 1.5% dextran sodium sulfate （DSS） freely for seven days and water normally for two weeks. Then， two cycles of ''DSS-drinking water'' were repeated. During the administration of DSS， mice in the normal group and model group were given gavage in equal doses of pure water. Mice in the mesalazine group were given 150 mg·kg-1·d-1 mesalamine suspension for gavage， and mice in the high- and low-dose Huangqintang groups were given 18 and 9 g·kg-1·d-1 Huangqintang for gavage， respectively. Each group was given one dose daily until the end of three cycles. After the intervention， the body weight， colon length， and number of colon tumors in each group were measured， and disease activity index （DAI） scores were performed. The serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-10 （IL-10）， and gastrointestinal tumor marker carbohydrate antigen-199 （CA199） were detected by enzyme linked immunosorbent assay （ELISA）. The colonic lesions were observed by hematoxylin-eosin （HE） staining. The expression of proliferative cell-associated antigen （Ki67） was observed by immunohistochemistry. The expression of T lymphocyte subsets （CD3+， CD4+， CD8+， and CD49b+） in mouse plasma was detected by flow cytometry. Fluorescein isothiocyanate-D （FITC-D） content in mouse serum was detected by fluorescent labeling method. The Western blot method was used to detect the expression of Cyclin D1， cyclin-dependent kinase 2 （CDK2）， cyclin-dependent kinase 4 （CDK4）， and tightly junction-related Occludin and Claudin-1. ResultCompared with the normal group， the body weight of mice in the model group decreased. DAI score increased significantly， and the colon became shorter. Pro-inflammatory factors such as IL-6， TNF-α， and IL-1β increased， and IL-6 and TNF-α were significantly increased （P<0.05）. The inflammatory factor IL-4 （P<0.05） and IL-10 were significantly reduced， and the tumor marker CA199 was significantly increased （P<0.01）. HE staining showed that colon lesions， intestinal mucosal epithelial defects with a large number of inflammatory infiltrates， serious crypt structure damage， and glandular arrangement disorder were observed in the model group. Ki67 positive granules were expressed in large areas of colonic tissue. The serum CD4+ and CD4+/CD8+ of mice in the model group decreased significantly （P<0.05）， and CD8+ increased significantly （P<0.05）. The plasma content of FITC-D in the model group was significantly increased （P<0.05）， and the expression of Cyclin D1， CDK2， and CDK4 proteins in colon tissue was significantly increased （P<0.05， P<0.01）. In addition， the expression of Occludin and Claudin-1 was significantly decreased. Compared with the model group， the body weight of mice in the mesalazine group and the high- and low-dose Huangqintang groups increased. DAI score decreased， and the colon became longer. IL-6， TNF-α， and IL-1β expression decreased （P<0.05， P<0.01）， but there was no significant change in IL-4 and IL-10. The content of CA199 was significantly reduced （P<0.05）， and the colomatoid lesions and inflammatory infiltrates were reduced in the mesalazine group and the Huangqintang group. The crypt structure damage was lighter， and the positive expression of Ki67 was reduced. CD4+， CD4+/CD8+， and CD49b+ increased， and the difference was not statistically significant. FITC-D content decreased （P<0.05）. The expression of Cyclin D1， CDK2， and CDK4 decreased （P<0.05， P<0.01）， and Claudin-1 and Occludin protein expression increased in the high-dose Huangqintang group （P<0.05）. ConclusionHuangqintang has a certain delay and inhibitory effect on AOM/DSS-induced inflammatory cancer transformation， and its mechanism of action may be related to regulating immune function and inflammatory response， inhibiting the release of pro-inflammatory factors， repairing damaged intestinal barriers， inhibiting abnormal proliferation of colon cells， and intervening in the formation and development of CAC colon tumors.

Progress in research on hydrogel and medium permeability / 中国生物制品学杂志

@#As a new research field,gel has been paid more attention and widely used for studies on tissue engineering,drug delivery and biosensor. Hydrogel is the carrier of cells,while the cell survival and death are keys to the construction of tissues and organs. However,the cell viability and biological behavior are limited by the exchange of hydrogel and nutrients in medium. This review summarizes the types of hydrogel,exchange mode of hydrogel and nutrients in medium and the relevant influencing factors,which will provide a reference for the development and research of tissue bioengineering.

Bactericidal permeability increasing protein-anti-neutrophil cytoplasmic antibody- associated vasculitis complicated with bronchiectasis: a case report and literature review / 中华肾脏病杂志

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

Correlations between transepidermal water loss rates and stratum corneum hydration levels in healthy children / 中华皮肤科杂志

Objective:To determine whether the transepidermal water loss rate (TEWL) is correlated with the stratum corneum (SC) hydration level.Methods:Healthy children aged ≤ 17 years were enrolled from Medical Center for Public Health of Puning, 2 kindergartens and 2 primary schools, from October 2021 to June 2022. TEWL and SC hydration levels were measured on the left forearm and right anterior shank using a device for measuring skin physiological funcitons. Pearson correlation analysis was used to determine the correlations between TEWL and SC hydration levels in children of different ages and genders.Results:A total of 1 396 healthy children were enrolled, aged from 1 month to 17 years. Among them, 783 were male children and 613 were female children. In children aged 1 to < 12 months, no correlation was observed between TEWL and SC hydration levels on the forearms of male children, while TEWL was positively correlated with SC hydration levels on the anterior shanks of male children, as well as on the forearm and anterior shanks of female children ( r = 0.283, 0.404, 0.420, respectively, all P < 0.05) . In children aged 1 to 2 years, positive correlations were observed between the above two indicators on the anterior shanks of male children and forearms of female children ( r = 0.370, 0.419, respectively, both P < 0.01) , while there were no correlations between the two indicators on the anterior shanks of female children or forearms of male children. Positive correlations were observed between TEWL and SC hydration levels on both the forearms and anterior shanks of female children and the forearms of male children aged 3 to 5 years and 6 to 11 years ( r values ranging from 0.172 to 0.293, all P < 0.05) , but not on the anterior shanks of male children aged from 6 to 11 years. The group aged 12 to 17 years exhibited significantly positive correlations between TEWL and SC hydration levels on both the anterior shanks and forearms of male and female children ( r values ranging from 0.269 to 0.485, all P < 0.001) . Conclusion:SC hydration levels are positively correlated with TEWL on the anterior shanks and forearms of healthy children, and the degree of correlation tends to increase with age.

Experimental study on the value of enhanced MRI in evaluating the permeability of pancreatic ductal adenocarcinoma / 中华放射学杂志

Objective:To investigate the value of enhanced MRI in evaluating the tissue permeability of pancreatic ductal adenocarcinoma (PDAC) animal model.Methods:The experimental animals were 27 female C57BL/6 mice. The mice were divided into 3 groups with 9 mice in each group by random number method. Murine pancreatic adenocarcinoma (Panc02) and embryonic fibroblasts (NIH/3T3) were implanted subcutaneously at the ratio of 2∶1 and 1∶1 to establish PDAC models with different tissue permeability, which were low fibroblast group and high fibroblast group, respectively, and simple Panc02 implantation model was control group. The positive expression rate of α-smooth muscle actin (α-SMA), the positive expression rate of fibroblast activating protein (FAP), the coverage rate of collagen fibers, number of blood vessels and the long/short diameter of tissue vessels were quantitatively evaluated by tissue staining, and the tissue permeation efficiency was quantified by the average optical density (AOD) of tissue sections stained by Evans blue (EB). Enhanced MRI was performed on mice, and the enhancement degree and the enhancement rate of 20 min were obtained. One-way ANOVA was used to compare the overall differences of tumor histological indexes and MRI enhancement parameters in each group, and the correlation between the indexes was analyzed by Pearson correlation analysis. Multiple linear stepwise regression analysis was conducted with 20 min enhancement rate as dependent variable, while α-SMA positive expression rate, collagen fiber coverage rate and vascular long/short diameter as independent variables.Results:There were significant differences in AOD value, α-SMA positive expression rate, FAP positive expression rate, collagen fiber coverage rate, vascular long/short diameter, 20 min enhancement degree and 20 min enhancement rate among the three groups ( P<0.001), but there was no significant difference in the number of blood vessels ( P=0.650). The AOD value was negatively correlated with the positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels in PDAC model, respectively ( r=-0.888, P=0.001; r=-0.813, P=0.008; r=-0.915, P<0.001). The 20 min enhancement degree was positively correlated with AOD value ( r=0.954, P<0.001). The positive expression rate of α-SMA, collagen fiber coverage and vascular long/short diameter were negatively correlated with 20 min enhancement rate ( r=-0.901, P<0.001; r=-0.837, P=0.005; r=-0.880, P=0.002). The results of multiple linear stepwise regression analysis showed that the positive expression rate of α-SMA was an important influencing factor for the 20 min enhancement rate (R 2=0.813, P=0.001). Conclusions:The increase of fibroblast implantation ratio significantly decreased the permeation efficiency of tumor tissue. The positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels were negatively correlated with the permeation efficiency of tumor tissue. The 20 min enhancement degree was positively correlated with tissue permeation efficiency.

Predictive value of thrombus enhancement and thrombus permeability in cardioembolic stroke with acute middle cerebral artery occlusion based on CT / 中华放射学杂志

Objective:To investigate the predictive value of thrombus enhancement (TE) and thrombus permeability in cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.Methods:The clinical and image data of 93 patients with acute middle cerebral artery occlusion who were admitted to the First Affiliated Hospital of Soochow University within 12 hours after onset from January 2020 to July 2022 were retrospectively analyzed. According to the TOAST criteria, the patients were divided into the cardioembolism (CE) group (43 cases) and the large artery atherosclerosis (LAA) group (50 cases). All patients received noncontrast CT and CT angiography, and then thrombus permeability [thrombus attenuation increase (TAI), void fraction (ε)] and TE were assessed. Independent sample t-test, Mann-Whitney U test and χ2 test were used in univariable analysis between two groups. Multivariable logistic regression analysis was used to explore the independent influencing factors for cardioembolic stroke and establish a logistic model. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive value of TAI, ε, TE and the logistic model in cardioembolic thrombus with acute middle cerebral artery occlusion. Results:There were statistically significant differences in sex, atrial fibrillation, hypertension, diabetes mellitus, smoking, baseline National Institutes of health stroke scale (NIHSS), TAI, ε and TE between the CE group and the LAA group ( P<0.05). Binary logistics regression analysis showed that TAI (OR=1.300, 95%CI 1.147-1.473, P<0.001), hypertension (OR=0.116, 95%CI 0.025-0.535, P=0.006) and baseline NIHSS (OR=1.165, 95%CI 1.040-1.304, P=0.008) were independent influencing factors for cardioembolic thrombus. The ROC curve indicated that the logistic model predicted cardioembolic thrombus with the highest AUC of 0.907 (95%CI 0.848-0.966). TE predicted cardioembolic thrombus with the highest sensitivity of 90.7%. Conclusion:TE and thrombus permeability have application value for predicting cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.

Expression and role of deleted in malignant brain tumor protein 1 in acute respiratory distress syndrome rats induced by sepsis / 中华危重病急救医学

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.