[Clinical characteristics and T-lymphocyte subsets in 48 acquired immune deficiency syndrome patients with cytomegalovirus infections].

Objective: To investigate the clinical features and T lymphocytes subsets in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) infection. Methods: A total of 48 hospitalized patients with human immunodeficiency virus (HIV)-1/AIDS and CMV infections were recruited at Peking Union Medical College Hospital from Jan 2010 to Aug 2017. Their clinical features and immune function were retrospectively analyzed. Patients with only HIV/AIDS in previous study were recruited as controls. Results: All 48 patients were at C3 stage, including 36 men and 12 women. Five of them were younger than 30 years old, 33 cases within 31-50 years old, and 10 cases older than 50 years old. Thirty-five patients had CD(4)(+)T lymphocytes ≤ 50 cells/µl, 7 cases with CD(4)(+)T cells 51-100/µl, 3 cases with 101-200 cells/µl, and 3 cases over 200 cells/µl. As to CMV infections, there were 31 cases of CMV viremia, 1 case of CMV encephalitis, 1 case of CMV enteritis, 5 cases of CMV pneumonia, and 9 cases of CMV retinitis. Other opportunistic infections were also common including 16 cases of pneumocystis pneumonia, 9 cases of tuberculosis, 5 cases of syphilis, 18 cases of digestive tract fungal infections, 8 cases of pulmonary fungal infections, 2 cases of EB virus infections, 2 cases of HIV encephalopathy/progressive multifocal leukoencephalopathy (PML), 3 cases of cryptococcal meningitis, 1 case of toxoplasma infection. In group of both CMV and HIV/AIDS infections, 100% patients had inverted CD(4)(+)/CD(8)(+) ratio. The immune activation marker CD(8)(+)CD(38)(+)/CD(8)(+) was higher (61.6%-98.8%) with a median value of 91.2% in 40 patients. HLA-DR(+)CD(8)(+)/CD(8)(+), another marker for T cell activation, was 25.5%-98.0% in 44 patients with a median value of 60.3%. Thirty-six patients had both immune activation markers positive. There was no significant difference in counts of B cells, natural killer cells, CD(4)(+) T cells, CD(8)(+) T cells and immune activation subsets stratified by gender and age (P>0.05). Meanwhile, neither serum HIV viral load nor serum CMV viral load was correlated with HLA-DR(+)CD(8)(+)/CD(8)(+), CD(8)(+)CD(38)(+)/CD(8)(+), CD(4)(+)T cell counts, and CD(4)(+)/CD(8)(+) ratio in the CMV and HIV/AIDS co-infection group (all P>0.05), while HIV viral load in HIV/AIDS only group was significantly correlated with HLA-DR(+)CD(8)(+)T/CD(8)(+), CD(38)(+)CD(8)(+)/CD(8)(+), CD(4)(+) T cell counts, CD(4)(+)/CD(8)(+) ratio (r=0.473, 0.575, -0.767 and -0.678, respectively, all P<0.05). Conclusions: CMV infections develop in HIV patients with advanced stage. CMV infection can cause life-threatening multiple organ lesions, especially in those with CD(4)(+) T cells less than 100 cells/µl. It is of great importance to screen CMV-IgM, pp65 antigen, CMV DNA to make early diagnosis and treatment.

[Conventional and functional MRI features of parotid Warthin tumor: correlation with clinicopathological findings].

Objective: To assess the conventional and functional MRI features of parotid Warthin tumor (adenolymphoma) and to investigate the correlation between MRI and clinicopathological features which can provide evidence for clinical diagnosis and treatment. Methods: Sixty-seven patients with parotid Warthin tumor who were treated in the Department of Stomatology, The Fifth Clinical Medical College of Yangzhou University, Changshu No. 2 People's Hospital from June 2008 to April 2017 were included in this study. The retrospective study evaluated preoperative conventional and functional MRI features and clinicopathological findings of this group of patients. Among 67 patients (65 males, 2 females) with 92 lesions, there were 16 patients with multiple lesions and others with single lesion. Their age was (62.1±8.8) years, ranging from 42 to 84 years. According to pathological features, parotid Warthin tumor were classified into two types. Type Ⅰ was predominantly solid component which included completely solid or solid tumor with some cystic components. Type Ⅱ was predominantly cystic component which was characterized by big cyst with some solid components, and could be divided into capsule-like and scum-like cystic type, based on whether its interface of solid and cystic component was clear or not. On contrast-enhanced MRI, according to whether the lesion showed enhancement or not, solid or cystic component was defined. Results: Seventy-two lesions were located in the lower pole of the parotid gland, of which sixty-eight lesions were located in posterior inferior quadrant. In addition, sixteen lesions were located in the upper pole and four lesions in the middle. Because MRI features were consistent with pathological findings, parotid Warthin tumor were classified into solid (73) and cystic types (19). On T2WI, solid components showed isointense (92), whereas on T1WI cystic components demonstrated hyperintense (90). On contrast enhanced T1WI, solid types showed marginal vasculature sign (73), mild (69) or moderate (4) enhancement, whereas its cystic component showed no enhancement. On contrast enhanced T1WI, cystic types showed ring-like enhancement of cycle-wall and intra-cystic septal linear enhancement, whereas its solid components demonstrated mild enhancement (19). On diffusion weighted imaging, these masses demonstrated hyperintensity and lower apparent diffusion coefficient value indicating restricted diffusion (59/59). On dynamic contrast-enhanced-MRI, the masses showed "wash-out" pattern (28/29) or plateau pattern (1/29). Conclusions: Parotid Warthin tumor mainly occur in the posterior inferior quadrant of parotid gland and mostly in mid-aged or elder men. It has certain characteristics on conventional and function MRI. There is correlation between MRI and clinicopathological findings and it is useful for accurate diagnosis and treatment to understand these features.

IKK-ß mediates hydrogen peroxide induced cell death through p85 S6K1.

The IκB kinase (IKK)/NF-κB pathway has been shown to be a major regulator in cell survival. However, the mechanisms through which IKK mediates cell death are not clear. In this study, we showed that IKK-ß contributed to hydrogen peroxide (H(2)O(2))-induced cell death independent of the NF-κB pathway. Our results demonstrated that the pro-death function of IKK-ß under oxidative stress was mediated by p85 S6K1 (S6 kinase 1), but not p70 S6K1 through a rapamycin-insensitive and mammalian target of rapamycin complex 1 kinase-independent mechanism. We found that IKK-ß associated with p85, but not p70 S6K1, which was required for H(2)O(2)-induced activation of p85 S6K1. IKK-ß and p85 S6K1 contributed to H(2)O(2)-induced phosphorylation of Mdm2 (S166) and p53 accumulation. p85 S6K1 is critical for IKK-ß-mediated cell death. Thus, these findings established a novel oxidative stress-responsive pathway that involves IKK-ß, p85 S6K1 and Mdm2, which is response for H(2)O(2)-induced cell death. Our results have important implications for IKK-ß and p85 S6K1 as potential targets for the prevention of diseases involved in oxidative stress-induced aberrant cell death.

Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis.

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers. Arachidonic acid (AA) and its metabolites play critical role in the development of breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood. We found that the levels of AA and cytosolic phospholipase A2 (cPLA2) strongly correlated with the signaling activity of mTORC1 and mTORC2 as well as the expression levels of vascular epithelial growth factor (VEGF) in human breast tumor tissues. In cultured breast cancer cells, AA effectively activated both mTOR complex 1 (mTORC1) and mTORC2. Interestingly, AA-stimulated mTORC1 activation was independent of amino acids, phosphatidylinositol 3-kinase (PI3-K) and tuberous sclerosis complex 2 (TSC2), which suggests a novel mechanism for mTORC1 activation. Further studies revealed that AA stimulated mTORC1 activity through destabilization of mTOR-raptor association in ras homolog enriched in brain (Rheb)-dependent mechanism. Moreover, we showed that AA-stimulated cell proliferation and angiogenesis required mTOR activity and that the effect of AA was mediated by lipoxygenase (LOX) but not cyclooxygenase-2 (COX-2). In animal models, AA-enhanced incidences of rat mammary tumorigenesis, tumor weights and angiogenesis were inhibited by rapamycin. Our findings suggest that AA is an effective intracellular stimulus of mTOR and that AA-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer.