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 .

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.

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 investigate the value of MRI in thmmbolytic thempy of hyperacute cerebral arterial thrombosis.Methods One hundred and sixteen patients with acute cerebral arterial thrombosis were recruited.plain CT and multi.modal MRI were performed in all patients.Thirty-three patients with hyperacute cerebral infarction were treated bv recombinant tissue plasminogen activator(rt-PA) and followed-up periodically using MRI.Results The 33 patients with thrombolysis selected by MRI demonstrated clinical improvement.90 d moclified Rankin scale scores(mRs)were less than 2 and life quality Barthal indexes(BI)were from 80 to 100.The complication included one asymptomatic parenchymal hematoma(PH1)one weeks after thrombolytic therapy and 4(12.2%)hemorrhagic infarction(HI)6 to 24 hours after thrombolytic therapy.Condusions MRI has significant clinical value for the screening and follow-up of intravenous thrombolytic therapy of hyperacute ischemic stroke.MRI-based thrombolysis is a safe and effective method for hyperacute ischemic stroke.

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

Congenital esophageal atresia with or without tracheoesophageal fistula is a relatively common and serious congenital gastrointestinal anomaly, which can be surgically repaired to achieve long-term survival in the majority of patients.However, various consequent long-term complications would affect the physical and mental health of patients, thus inducing a decline in their quality of life.In this study, the present status and advances of diagnosis and treatment of these complications were reviewed, in an attempt to further explore the long-term complications after congenital esophageal atresia.

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.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.