Tumor microenvironment is composed by tumor cells,stromal cells,immune-inflammatory cells,extracellular matrix,soluble cytokine and so on.Previous studies focused on the biological behavior,genetic changes and related phenotypic changes of tumor cells,but tumor microenvironment is closely related with the tumor development and treatment resistance.In recent years,new studies have confirmed that tumor microenvironment is an important member of tumor,which play an important role in proliferation,invasion and proliferation of tumor cells.This article mainly introduces the tumor microenvironment features,tumor-associated macrophage and tumor-associated fibroblasts,which led to the radioresistance of tumor.

The effects of cyclosporine A on matrix metalloproteinases(MMP)-2 and-9 expressions in the cardiac muscle of streptozocin-induced diabetic rats were investigated.The expressions of MMP-2 and MMP-9 mRNA and proteins in the cardiac muscle of diabetic rats were significantly upregulated,which could be decreasedby cyclosporine A(P＜0.05 or P＜0.01).The results suggest that cyclosporine A may effectively ameliorate the injuries of diabetic cardiomyopathy.

Objective To study the autoimmune injuries on diabetic retinopathy(DR)and the protective effects of immunosuppre8sive therapy with eyelosporine A(CsA) on the DR of streptozotocin(STZ)-induced diabetic rats.Methods STZ-induced diabetic rats were randomly divided into 3 groups: group 1:diabetic group without any treatment;group 2:insulin-treated group;group 3:CsA-treated group which was further divided into 2 subgroups:subgroup A:CsA was given 1 week before hyperglycemia appeared and subgroup B:CsA was given one week after hyperglycemia appeared.Subgroup A and subgroup B were further subdivided into 3 groups respectively,based on the dose of CsA(1,4 and 8 mg·kg-1·d-1).As a control group,normal rats were also simultaneously monitored.The pathologic changes in the retina were investigated with HE stain and the deposition of immunoglobulins was detected with immunohistochemistry and immunofluorescent microscopy.Results After 8 week,the deposition of IgG, IgA and IgM was quite significant in the retina of diabetic rats.The data also suggested that insulin treatment had no effects on the DR.In contrast,with CsA intervention,the deposition of immunoglobulins on the retina of diabetic rats vanished.Conclusions Autoimmune injuries were shown,in the present study,to play a critical role in the pathogenesis of diabetic retinopathy.Immunosuppressive treatment with CsA showed protective effects by inhibiting the deposition of immunoglobulins in the retina of diabetic rats.

Objective To study the effects of MF59 in combination with heat-killed BCG ( hBCG) as adjuvant on the immunogenicity of Mycobacterium tuberculosis fusion protein PstS1-LEP.Methods BALB/c mice were divided into six groups from group 1 through group 6.They were immunized with PstS1-LEP+MF59 ( group 1 ) , PstS1-LEP+MF59/hBCG ( group 2 ) , PstS1-LEP+hBCG ( group 3 ) , MF59 ( group 4 ) , PstS1-LEP (group 5) and hBCG (group 6) for three times at intervals of two weeks , respectively.The mice were sac-rificed two weeks after the last immunization .The serum samples were collected for antibodies detection .The splenic lymphocytes and peritoneal macrophages were isolated and cultured with PstS 1-LEP.Indirect ELISA and sandwich ELISA were used to detect PstS 1-LEP-specific antibodies and cytokines in the supernatants of culture , respectively.Results The level of IFN-γ, IL-1β, IgG, IgG1 and IgG2a in group 1 were higher than those in groups 4, 5 and 6 (P<0.05).The level of IL-2 and IL-4 in group 1 were higher than those in groups 4 and 6 (P<0.05).The level of IFN-γ, IL-1β, IL-12, IgG, IgG1 and IgG2a in group 2 were higher than those in groups 4, 5 and 6 (P<0.05).The level of IL-2 was higher in group 2 than that in groups 4 and 6 (P<0.05). The level of IL-4 in group 3 was higher than that in group 4 ( P=0.05 ) .The level of IL-1βin group 3 were higher than that in groups 4 and 5 ( P<0.05 ) .The level of IgG was higher in group 3 than that in groups 4 and 6 (P<0.05).IgG1 level in group C was up-regulated in comparison with that in groups 4, 5 and 6 (P<0.05 ) .Conclusion hBCG as PstS1-LEP adjuvant induces a shift towards Th 2-type immune response , while MF59 induces Th1/Th2-type immune response.The combination of MF59 and hBCG inhibits the secretion of IL-4 by spleen lymphocytes , but enhances the secretion of IL-12 by macrophage .

Choriocarcinoma ; diagnosis ; Female ; Humans ; Liver ; pathology ; Pregnancy

BACKGROUNDTo study the effect of DTB against HIV-1, for developing anti-HIV drugs.

METHODSDifferent concentration of DTB was added to cell culture system after viral inoculation, MTT staining method for viable cells (MTT assay) and p24 (ELISA) were used as markers to monitor the viral replication.

RESULTSThe inhibition rates of DTB at concentrations 160, 80, and 40mg/ml were 93.0%, 56.2% and 18.1%, respectively.

CONCLUSIONSDTB could effectively inhibit HIV-1 in vitro.

Anti-HIV Agents ; pharmacology ; Bilirubin ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; HIV-1 ; drug effects ; Humans ; In Vitro Techniques

OBJECTIVETo establish red-green dual-color fluorescence glioma model in nude mice and to explore its practical values.

METHODSCM-DiI-stained rat glioma C6 cells (C6-CM- DiI cells) expressing red fluorescence were inoculated into the brain of athymic nude mice expressing green fluorescence protein (NC-C57BL/6J-EGFP). Then the whole-body dual-color fluorescence imaging was detected dynamically. Finally whole brains of the tumor-bearing mice were removed and 5 µm thick serial frozen slices were made. Light microscopy, fluorescence microscopy and confocal laser scanning microscopy were performed to observe the transplanted tumor tissue structure and fluorescent cells.

RESULTSTumor mass with red fluorescence increased gradually under continuous in-vivo fluorescence imaging monitoring. Under the fluorescence microscope, cells with red, green and yellow fluorescence were observed in the frozen sections of transplanted tumor tissue and the mutual structural relationship among them could be defined. The tumor cells migration, implantation and cell fusion between transplanted tumor cells and host cells could be observed. It could be distinguished according to the fluorescence, that blood vessels of tumor-origin displayed red fluorescence, blood vessels of host-origin displayed green fluorescence and mosaic blood vessels appeared yellow fluorescence. It was depicted that host innate astrocytes and oligodendrocytes in the microenvironment at the tumor periphery could be activated and dedifferentiated into nestin-positive cells.

CONCLUSIONSIn contrast to traditional animal model, the dual-color fluorescence imaging of nude mouse models of glioma possesses enormous advantages in investigating tumor mass in-vivo fluorescence imaging, tumor cells migration and metastasis, tumor angiogenesis and reactive activation of host innate cells in the microenvironment at tumor periphery, thus, has highly practical application value.

Animals ; Astrocytes ; metabolism ; Brain Neoplasms ; blood supply ; metabolism ; pathology ; ultrastructure ; Carbocyanines ; metabolism ; Cell Fusion ; Cell Line, Tumor ; Cell Movement ; Disease Models, Animal ; Fluorescent Dyes ; metabolism ; Glioma ; blood supply ; metabolism ; pathology ; ultrastructure ; Green Fluorescent Proteins ; metabolism ; Luminescent Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Microscopy, Confocal ; Microscopy, Fluorescence ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Nestin ; metabolism ; Oligodendroglia ; metabolism ; Rats

Objective:To study the duration of invasive mechanical ventilation (MV) and its influencing factors after neonatal abdominal surgery under general anesthesia in neonatal intensive care unit (NICU).Methods:From January 2018 to December 2020, neonates received abdominal surgery under general anesthesia and needed endotracheal intubation and MV after surgery in NICU of our hospital were retrospectively studied. According to MV duration, the neonates were assigned into <72 h group and ≥72 h group. Multivariate logistic regression was used to analyze the risk factors of postoperative MV duration.Results:A total of 113 neonates were enrolled, including 57 male (50.4%) and 56 female (49.6%). The gestational age was (35.7±3.6) weeks, the birth weight was (2 497±933) g, the average operation age was 9.9(3.6, 22.2) d and the average hospital stay was 22.0(12.0,37.0) d. Congenital intestinal obstruction (37/113, 32.7%) was the most common diagnoses on discharge, followed by neonatal necrotizing enterocolitis(28/113,24.8%) and gastrointestinal perforation (18/113,15.0%). The duration of operation was 80.0 (55.8,117.3) min. All neonates needed MV with endotracheal intubation. The duration of postoperative respiratory support was 30.0(7.0,84.5) h. 48 neonates (42.5%) had endotracheal intubation removed within 24 h after surgery. Multivariate logistic regression analysis showed that preoperative respiratory support ( P=0.004), congenital heart disease( P=0.013) and intravenous midazolam ( P=0.032) were independent risk factors for prolonged postoperative MV. Conclusions:The need of preoperative respiratory support, congential heart disease and intravenous midazolam were independent risk factors for the duration of postoperative MV after neonatal abdominal surgery under general anesthesia.

Clinical phenotypes and gene characteristics of a patient diagnosed with Mowat-Wilson syndrome (MWS) with Hirschsprung′s disease (HSCR) and vaginal atresia in the Department of Neonatal Surgery, Beijing Children′s Hospital, Capital Medical University in March 2021 were analyzed retrospectively.The eight-month-old girl was admitted to the hospital with symptoms of constipation for nine days and abdominal distension for two days.Lower digestive tract radiography and rectal mucosa biopsy results suggested HSCR.The child also had specific facial features and motor development delay.Whole exome test showed a de novo heterozygous mutation, ZEB2 gene c. 2761C>T (p.R921*). After laparoscopic-assisted Soave procedure, the child had normal bowel movements, and no surgery-related compli-cations occurred during the follow-up period.The child′s motor development improved after rehabilitation treatment.According to literature review, 2 female cases show similar clinical manifestations to this girl, but the genotypes were different.This patient expands the clinical phenotype of ZEB2 gene pathogenicity.