The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.

Objective:To evaluate the effect of perioperative application of hydroxychloroquine on the prognosis of patients undergoing cardiac surgery.Methods:All SLE patients in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University who took hydroxychloroquine and glucocorticoid for more than 7 days before operation were enrolled in the observation group(28 cases), including 3 males and 25 females, aged(38.3±8.2)years old. Patients who did not use hydroxychloroquine but only used glucocorticoid before operation were included in the control group(24 cases), including 2 males and 22 females, aged(37.9 ±9.8)years old. There was no significant difference in preoperative clinical data between the two groups in terms of sex, age, BMI, course of systemic lupus erythematosus, hemoglobin, albumin, C-reactive protein, ALT, serum creatinine, ejection fraction, diabetes, hypertension, hyperlipidemia, smoking, alcoholism, preoperative atrial arrhythmia, ventricular arrhythmia, atrioventricular block and so on. The constituent ratio of preoperative operation plan was basically the same between the two groups. The postoperative complications and survival of the two groups were compared.Results:There was no significant difference in early clinical indexes between the two groups, such as cardiopulmonary bypass time( t=0.12, P=0.19), chest drainage volume( t=0.30, P=0.77), second thoracotomy hemostasis( χ2=1.17, P=0.46). There was no significant difference in drug-related complications such as new retinopathy, myocardial concentric hypertrophy, atrial arrhythmia( χ2=1.27, P=0.26), ventricular arrhythmia( χ2=0.98, P=0.32), atrioventricular block( χ2=0.06, P=0.82) and other drug-related complications between the observation group and the control group. There was no significant difference between the two groups in postoperative acute heart failure( χ2=1.17, P=0.28), acute liver insufficiency( χ2=1.17, P=0.28), sternal infection and IABP use( χ2=0.47, P=0.50). Compared with the control group, the incidence of acute renal insufficiency after operation was lower in the observation group( χ2=4.51, P=0.04). The incidence of new postoperative pneumonia was lower( χ2=8.26, P=0.01). The length of postoperative antibiotic use, the length of postoperative ICU hospital stay, the postoperative hospital stay and the total cost of hospitalization in the observation group were significantly less than those in the control group( z=2.71, 2.09, 2.02, 2.02, P=0.01, 0.04, 0.04, 0.04). Compared with the control group, the in-hospital mortality rate of patients in the observation group was lower than that in the control group(3.6% vs. 12.5%, χ2=0.47, P=0.50), and the 6-month and 1-year survival rates of the observation group were higher than those of the control group(92.9% vs.83.3%, 92.9% vs.79.2%; χ2=0.41, 2.17; P=0.53, 0.34), but the difference was not statistically significant. Conclusion:Perioperative administration of hydroxychloroquine can significantly reduce the incidence of postoperative acute renal insufficiency and pneumonia, reduce the duration of postoperative antibiotic use, postoperative ICU hospital stay, postoperative hospital stay, and the cost of hospitalization. Hydroxychloroquine may reduce the in-hospital mortality and improve the long-term survival rate after cardiac surgery, but long-term large sample clinical studies are still needed.

Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.

Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype.Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients.A 43-year-old patient, who was socially female, was first admitted to gastroenterology department due to recurrent ascites and occasional abdominal pain with unknown origin.Taking physical examination, ultrasonography, karyotype analysis and sex hormone levels into consideration, the overall manifestations revealed the typical clinical features of complete androgen insensitivity syndrome.After that she was transferred to urology department for laparoscopic gonadectomy.During the surgery, doctors found that there was a vesical fistula on the upper wall near the conjunction between the bladder and ligamenta umbilicale medium, which explained the recurrent ascites for more than 4 years.After resecting the testicles and the tissues around the vesical fistula for histopathology, the result suggested Sertoli cell adenoma, hyperplastic Leydig cells and urothelium atypical hyperplasia.Hormone replacement therapy was given right after discharge.The hormone levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were modulated by the dysfunction of androgen production after gonadectomy and hormone replacement therapy together with psychotherapy could stabilize her hormone levels and improve the quality of her life.The patient was suspicious of AIS family history and the pedigree was made to analyze her family which was possibly X-linked recessive pattern.We propose three possible hypotheses of the fistula, which are direct surgical injury, recurrence of bladder cancer and congenital urachal anomalies.But whether it is relevant between urachal anomalies and AIS is yet to be discovered.

Fluconazole,the third generation of triazole-antifungal drug,becomes the first choice in the treatment of fun-gal infection due to its broad antifungal spectrum,good water solubility and low toxicity.With an increasingly drug-resistant strain,developing new fluconazole derivatives is becoming an attractive topic.This review mainly indicates that people can get new fluconazole derivatives used by clinic through structural modification of fluconazole,which will give clues for advanced re-search.

Objective Anthrax is an anthropozoonosis caused by the bacterium Bacillus anthracis .Bacillus anthracis is an aerobic ,spore-forming ,rod-shaped bacterium ,which infects human through ingestion or inhalation of the spores .The exos-porium of spores of Bacillus anthracis contains tetrasaccharide antigen with specific chemical structure ,which can be used in preparation of glycoconjugates vaccines ,inducing an immune response .This paper reviewed articles in the last decade that re-ported research advances in chemical synthesis of anthrax tetrasaccharide ,presented the methods for synthesis ,and compared the advantages and limitations among different methods .