ABSTRACT
Objective To compare the effects of different local intervention temperatures of pressure ulcer on endoplasmic reticulum stress (ERS) and apoptosis in rats, and to provide an experimental evidence for clinical prevention and treatment of pressure ulcer. Methods The rat model of pressure ulcer was established by ischemia reperfusion, and a total of 40 SPF adult, male SD rats were divided into 4 groups: the sham group (anesthesia only, without other treatment), model group (ischemia at 22℃ for 1 h and reperfusion at 22℃ as one cycle, repeated for 5 cycles), high-temperature intervention group (ischemia at 22℃ for 1 h and reperfusion at 32℃ as one cycle, repeated for 5 cycles) and low-temperature intervention group (ischemia at 22℃ for 1 h and reperfusion at 12℃ as one cycle, repeated for 5 cycles). At the end of the experiment, muscle tissues at the sites under pressure of the rats were taken on ice. The pathological changes of skeletal muscle tissues were observed by HE staining. The expression levels of ERS-related proteins GRP78, caspase-12 and CHOP were detected by Western blot, and the expression of caspase-12 and CHOP was also observed by immunofluorescence. Moreover, apoptosis in the skeletal muscle cells was examined by TUNEL staining. Results Compared with the model group, skeletal muscle cell damages became more severe and apoptotic cells were increased in the high-temperature intervention group. Besides, the results of the immunofluorescence assay showed an increased positive expression of caspase-12 and CHOP, and the results of Western blot showed that the expression levels of GRP78, caspase-12 and CHOP were all higher than those of the model group (P＜ 0. 05). In contrast, skeletal muscle cell damages were alliviated and apoptotic cells were reduced in the low-temperature intervention group. Meanwhile, the positive expression of caspase-12 and CHOP was decreased, as shown by immunofluorescence, and all the expression levels of GRP78, caspase-12 and CHOP detected by Western blot were lower than the control group (P ＜ 0. 05). Conclusions Local low-temperature intervention can alleviate the pressure ulcer damages in rats through inhibition of the ERS-mediated apoptotic pathway. Local high-temperature intervention may exacerbate the pressure ulcer damages in rats by activating the ERS-mediated apoptotic pathway and promoting cell apoptosis. Local low-temperature intervention may be promising in clinical prevention and treatment of pressure ulcer.
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Objective@#To investigate the clinical and laboratory features of patients with liver disease and positive anti-liver/kidney microsomal-1 (anti-LKM-1) antibody, and to provide a reference for clinical diagnosis and differential diagnosis.@*Methods@#The clinical data of patients with positive anti-LKM-1 antibody who were treated in our hospital from 2006 to 2016 were collected, and clinical and laboratory features were analyzed and compared. An analysis was also performed for special cases.@*Results@#The measurement of related autoantibodies was performed for about 100 thousand case-times, and 15 patients were found to have positive anti-LKM-1 antibody. Among the 15 patients, 7 were diagnosed with type 2 autoimmune hepatitis (AIH) with an age of 11.0 ± 9.0 years and were all adolescents with acute onset; 8 were diagnosed with hepatitis C with an age of 51.5 ± 9.0 years, among whom 7 were middle-aged patients and 1 was a child aged 12 years, and all of them had an insidious onset. Compared with the patients with hepatitis C, the AIH patients had significantly higher levels of alanine aminotransferase (1 003.9 ± 904.3 U/L vs 57.0 ± 84.1 U/L, P < 0.05), aspartate aminotransferase (410.7 ± 660.3 U/L vs 34.9 ± 42.9 U/L, P < 0.05), and total bilirubin (98.0 ± 191.0 μmol/L vs 15.4 ± 6.0 μmol/L, P < 0.05). There was a reduction in immunoglobulin G after the treatment with immunosuppressant, compared with the baseline. Of all 8 patients with hepatitis C, 6 received antiviral therapy with interferon and ribavirin, and 5 out of them achieved complete response, among whom 4 had a reduction in the level of anti-LKM-1 antibody after treatment; however, a 12-year-old child developed liver failure after interferon treatment and died eventually.@*Conclusion@#Positive anti-LKM-1 antibody is commonly seen in patients with type 2 AIH or hepatitis C, but there are differences between these two groups of patients in terms of age, disease onset, liver function, and the level of anti-LKM-1 antibody. The hepatitis C patients with a confirmed diagnosis and exclusion of autoimmune hepatitis can achieve good response to interferon under close monitoring, even if anti-LKM-1 antibody is positive. As for adolescent patients with hepatitis C and positive anti-LKM-1 antibody, the possibility of AIH should be excluded.
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Objective To investigate the effect of short stature homeobox (SHOX) gene promoter-372G →A mutation on the promoter activity and its mechanism.Methods The luciferase report gene vectors containing human SHOX gene promoter-372G or -372A were contructed.Their transcription activities were detected in chicken chondrocytes.Double-stranded DNA probes containing-372G or-372A were produced by PCR,and used for detecting the affinity with nuclear transcription factors by electrophoretic mobility shift assay(EMSA).Results The transcription activity in a-372A promoter construct was significantly higher than that in the wild type-372G (P<0.01).The result of EMSA showed that-372A gene mutation resulted in loss of the binding affinity to nuclear transcription factors.Conclusion The-372A mutation increases SHOX promoter activity with decreased DNA binding affinity to transcription factors,which may contribute to impaired long bone growth in patients with idio pathic short stature.
ABSTRACT
Objective To investigate clinical features and immunologic status in human immunodeficiency virus(HIV)/hepatitis C virus(HCV)co-infected and HIV mono-infected patients,and to assess the possible interactions between HCV and HIV.Methods Fifty-nine patients with HIV/HCV co infection were enrolled.The control group was consisted of 38 patients with HIV monoinfection.The liver function,peripheral blood T cell subgroups(CD4+and CD8+)cell count and HIV RNA level were compared between these two groups.Peripheral blood mononuclear cells(PBMCs) were analyzed by interferon-γ enzyme-linked immunospot(ELISPOT)using a panel of HIV antigens.Results The frequency of HIV/HCV co-infection was 60.8%.Both alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in HIV/HCV co-infection group were significantly higher than those in HIV mono infection group(49.8 U/Lvs 23.6 U/L,49.1 U/L vs 32.3 U/L,P=0.000,0.013).Platelet count was lower in HlV/HCV co-infection group than in HIV group[(167.3±59.2)×109/Lvs(198.0±63.9)×109/L,P=0.040].CD4+cell and CD8+cell counts were not significantly different between co-infection group and HIV group.The HIV RNA level was lower in HIV/HCV co-infection group than in HIV group [(4. 046 ± 0. 541 ) log10 copy/mL vs (4. 394 ± 0. 507) log10copy/mL, P=0. 018]. The intensity of HIV-specific cytotoxic T lymphocyte (CTL) response to HIVGag overlapping peptides in HIV/HCV co-infection group (mean bank 30.85) was lower than HIV group (mean bank 44.34). The number of the HIV-specific CTL cell in HIV/HCV co-infection group (4.60±5.52) was slightly lower than HIV group (6.24±6.93) without significant difference.Albumin was negatively correlated with HCV RNA in HIV/HCV co-infection group (r=-0. 540). A positive correlation was found between platelet and peripheral blood CD4+ cell counts (P=-0. 040). No linear correlation was found between HCV viral load, HIV viral load and peripheral blood CD4+ cell counts. Conclusions The prevalence of HCV co-infection is relatively high. The cellular immunity status in these co-infected patients is relatively poor.