Thrombotic antiphospholipid syndrome in a child with human immunodeficiency virus: a rare case report.

BACKGROUND: Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children. A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments. CONCLUSION: When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.

AIDS-associated Talaromyces marneffei central nervous system infection in patients of southwestern China.

BACKGROUND: The clinical and laboratory characteristics of AIDS-associated Talaromyces marneffei infection, a rare but a fatal mycosis disease of the central nervous system, remain unclear. CASE PRESENTATION: Herein, we conducted a retrospective study of ten AIDS patients with cerebrospinal fluid culture-confirmed central nervous system infection caused by Talaromyces marneffei. All 10 patients were promptly treated with antifungal treatment for a prolonged duration and early antiviral therapy (ART). Among them, seven patients were farmers. Nine patients were discharged after full recovery, while one patient died during hospitalization, resulting in a mortality rate of 10%. All patients initially presented symptoms and signs of an increase in intracranial pressure, mainly manifesting as headache, dizziness, vomiting, fever, decreased muscle strength, diplopia or even altered consciousness with seizures in severe patients. Nine patients (90%) showed lateral ventricle dilatation or intracranial infectious lesions on brain CT. Cerebrospinal fluid findings included elevated intracranial pressure, increased leukocyte count, low glucose, low chloride and high cerebrospinal fluid protein. The median CD4+ T count of patients was 104 cells/µL (IQR, 36-224 cells/µL) at the onset of the disease. The CD4+ T cell counts of three patients who eventually died were significantly lower (W = 6.00, p = 0.020) than those of the patients who survived. CONCLUSIONS: The common clinical symptoms of T. marneffei central nervous system infection are associated with high intracranial pressure and intracranial infectious lesions. Earlier recognition and diagnosis and a prolonged course of amphotericin B treatment followed by itraconazole combined with early ART might reduce the mortality rate.

MiR-675 is frequently overexpressed in gastric cancer and enhances cell proliferation and invasion via targeting a potent anti-tumor gene PITX1.

BACKGROUND: Gastric cancer (GC) is a common malignancy around the world. Irregular expression of microRNAs (miRNAs) contributes to the progression of malignancies. Our study illustrated that miR-675 facilitates GC proliferation and invasion via targeting paired-like homeodomain transcription factor 1 (PITX1) and promoting epithelial-mesenchymal transition (EMT) as well as Wnt/ß-catenin signaling pathway. METHODS: We collected the RNA-seq data of GC and normal stomach tissues from TCGA database to analyze the expression of miR-675 and PITX1. Kaplan-Meier plotter on line tool was used to analyze the association between miR-675 or PITX1 expression and the overall survival of GC patients. The biological function of miR-675 in GC cells was evaluated via altering its expression using miR-675 agomiR or antamiR. Dual-luciferase reporter assay was applied for verifying whether miR-675 could direct bind to 3'UTR of PITX1. Rescue assays were applied for characterizing the effects of miR-675/PITX1 axis on GC growth and invasion. Western blot was performed to evaluate the protein expression levels of PITX1, EMT-related and Wnt signaling-related proteins. RESULTS: Our results showed that miR-675 is up-regulated and predictive of worse prognosis in GC patients. Overexpression of miR-675 in AGS cells notably promoted cell proliferation, migration and invasion, whilst down-regulation of miR-675 in SGC-7901 cells gained the opposite results. PITX1 is down-regulated in GC and identified as a direct target of miR-675. Overexpression of PITX1 in AGS cells reverses cell viability and invasion that enhanced by miR-675 up-regulation. Conversely, depletion of PITX1 in SGC-7901 cells rescues cell viability and invasion that inhibited by miR-675 down-regulation. Western bolt results revealed that miR-675 positively regulated EMT and Wnt/ß-catenin signaling pathway in GC cells via targeting PITX1. CONCLUSIONS: Our study emphasized the functional mechanism of miR-675 in GC and intimated that miR-675/PITX1 axis possibly affects proliferative and invasive properties of GC cells via regulating EMT and Wnt/ß-catenin signaling pathway. Furthermore, miR-675 and PITX1 may be served as early diagnostic markers as well as therapeutic targets for GC.

Innate Immunity Acts as the Major Regulator in Talaromyces marneffei Coinfected AIDS Patients: Cytokine Profile Surveillance During Initial 6-Month Antifungal Therapy.

BACKGROUND: Talaromycosis caused by Talaromyces marneffei infection is a fatal systemic mycosis in immunosuppressed individuals, such as patients with AIDS. Cytokines and immunocytes play a central role against fungus infection. However, how the host immune system responds to infection and treatment has not been reported to date. METHODS: Forty-one Talaromyces marneffei coinfected AIDS patients were followed up, their immunocytes and cytokine profiles were obtained at different antifungal treatment stages, and data on clinical features and laboratory examinations were collected. Correlation analysis was used to identify factors associated with host immunity against Talaromyces marneffei infection in AIDS patients. RESULTS: Common diseases and conditions of these 41 patients were lymphadenopathy, hepatomegaly, and splenomegaly. CD4+ T cells were extremely low in all of them. Moreover, significant increases of proinflammatory cytokines (IL-12, IL-17A, TNF-α, IFN-γ, IL-18, and IL-1ß), anti-inflammatory cytokines (IL-10), and chemokines (IP-10) were observed in talaromycosis before treatment (P < .05), comparing to both AIDS patients and healthy controls. The cytokines IL-6, IL-8, TNF-α, IL-18, IL-17A, IL-7, IP-10, and IL-1ß reached peak levels 3 days after initial antifungal therapy, and then gradually decreased. The symptoms of the patients gradually decreased. Furthermore, patients who died showed the highest levels of IL-6, TNF-α, IL-8, IL-1ß, and IP-10, which were 1.4- to 164-fold higher than in surviving patients. CONCLUSIONS: Our findings indicate that innate immune-cell-derived cytokines are critical for host defense against AIDS-associated Talaromyces marneffei infection; furthermore, excessive inflammatory cytokines are associated with poor outcomes.

[Expressions of fractalkine and CD11c on common carotid artery atherosclerotic plaques from apoE(-/-) mice].

OBJECTIVE: To explore the association of fractalkine (FKN) and CD11c expressions oncommon carotid artery atherosclerotic plaques from apoE(-/-) mice with the severity of atherosclerotic lesions. METHODS: Totally 24 apoE(-/-) mice were divided into two groups and fed on a high-fat diet or a normal diet for 12 weeks. Then the blood lipids as well as the plaque area and vascular stenosis rate of the common carotid artery were measured to evaluate the severity of atherosclerotic lesions of the animals. Moreover, immunohistochemical staining was performed to examine the levels of FKN and CD11c expression. RESULTS: The plaque areas and vascular stenosis rates of the common carotid artery in the experimental group were remarkably larger than those in control group (about 4-fold and 2-fold, respectively). The level of FKN expression in the experimental group was 2 times of that in the control group (P<0.05), and the number of CD11c (+) cells in the plaques in the experimental group was about 4 times of than in the control group (P<0.05). CONCLUSION: The expressions of chemokine and FKN remarkably increase in apoE (-/-) atherosclerotic plaques, suggesting that chemokine and FKN may paly important roles in the development of atherosclerosis.