[Characteristics of serum bile acids among healthy children in Zhejiang province].

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Association between B7-H1 expression and bladder cancer: a meta-analysis.

B7 homolog 1 (B7-H1), which is also known as programmed death-L1, is an important member of the B7/CD28 costimulatory factor superfamily, which are emerging as important mediators of various host immune responses. B7-H1 is differentially expressed in various cell subsets and to different extents in human and murine cells. Human B7-H1 is constitutively expressed at low levels in dendritic cells and activated T cells (compared with high expression in activated murine T cells) and is highly expressed in monocytes and tumor cells. We conducted a meta-analysis to explore the association between B7-H1 expression and bladder cancer risk. Two groups were examined, including 352 bladder cancer cases and 60 healthy controls. Meta-analysis results revealed that B7-H1 expression is positively associated with bladder cancer and is strongly associated with the clinical stage of bladder cancer. However, no significant difference was found with respect to gender and the pathological grade of bladder cancer.

Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8(+) T cell recognition.

CD8(+) T lymphocyte responses are a critical arm of the immune response to respiratory virus infection and may play a role in the pathogenesis of interstitial lung disease. We have shown that CD8(+) T cells induce significant lung injury in the absence of virus infection by adoptive transfer into mice with alveolar expression of a viral transgene. The injury is characterized by the parenchymal infiltration of host cells, primarily macrophages, which correlates with physiologic deficits in transgenic animals. CD8(+) T cell-mediated lung injury can occur in the absence of perforin and Fas expression as long as TNF-alpha is available. Here, we show that the effect of TNF-alpha expressed by CD8(+) T cells is mediated not exclusively by cytotoxicity, but also through the activation of alveolar target cells and their expression of inflammatory mediators. CD8(+) T cell recognition of alveolar cells in vitro triggered monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) expression in the targets, which was mediated by TNF-alpha. Antigen-dependent alveolar MCP-1 expression was observed in vivo as early as 3 hours after CD8(+) T cell transfer and depended upon TNF-R1 expression in transgenic recipients. MCP-1 neutralization significantly reduced parenchymal infiltration after T cell transfer. We conclude that alveolar epithelial cells actively participate in the inflammation and lung injury associated with CD8(+) T cell recognition of alveolar antigens.

Perforin-independent CD8(+) T-cell-mediated cytotoxicity of alveolar epithelial cells is preferentially mediated by tumor necrosis factor-alpha: relative insensitivity to Fas ligand.

CD8(+) T cells appear to play an important pathophysiologic role in many inflammatory lung diseases. The primary effector function of this T-cell subset is cytolysis of virus-infected cells, and it is widely believed that there are two primary molecular mechanisms by which this occurs: the perforin/granzyme-mediated pathway of cytolysis, and the Fas ligand (FasL)-Fas (CD95/APO-1) pathway of induction of target-cell apoptosis. This conclusion is based primarily on data obtained with hematopoetic cell lines as target cells. There is also a growing body of evidence that Fas is involved in the transduction of apoptotic signals in a variety of inflammatory disease states, particularly involving the liver and the lung. In the study reported here we took advantage of a novel in vitro assay to directly assess the effector mechanisms employed in CD8(+) T-cell-mediated cytolysis of alveolar epithelial cells. We present evidence that FasL-induced, Fas-mediated apoptosis does not directly contribute to T-cell-mediated cytolysis of alveolar epithelial-derived cells, even though Fas is expressed and functional on these cells. We also demonstrated that the perforin-independent cytolytic activity of CD8(+) T cells against alveolar epithelial-derived cells is explained entirely by tumor necrosis factor-alpha (TNF-alpha), which is expressed on CD8(+) T cells. Furthermore, we show that bystander cytolysis of alveolar epithelial-derived cells by antiviral CD8(+) T cells is entirely perforin-independent. This activity is mediated exclusively by TNF-alpha. Both alveolar epithelial-derived cells and primary murine type II cells show susceptibility to apoptosis triggered by soluble TNF-alpha, without the need for transcriptional or translational inhibition. We also confirmed the resistance of alveolar type II cells to FasL in vivo by performing adoptive transfer of perforin-deficient antiviral CD8(+) T cells into transgenic mice expressing a target antigen in type II epithelial cells. Significant lung injury developed in the transgenic CD8(+) T-cell recipients, whether or not Fas was expressed in these animals. Furthermore, preincubation of the T cells with antibody to TNF-alpha completely abolished the injury. These results suggest that alveolar epithelial cells are relatively sensitive to T cell-triggered, TNF-alpha-mediated apoptosis, and resistant to apoptosis triggered by FasL. These observations may have important ramifications for understanding of the pathophysiology of interstitial and inflammatory lung diseases.

Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease.

CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell infiltration that correlated with restrictive pulmonary mechanics and a progressive diffusion impairment. These results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.

[Study and application of "binocular aniseikonia test chart"].

With the help of this chart, the image incongruity of simultaneous perception, fusion and stereoscopic vision can be precisely determined. It can objectively evaluate the binocular visual function and possesses important significance for the diagnosis and treatment of anisometropia, amblyopia, strabismus and visual fatigue.

[Lyme disease in China and its ocular manifestations].

The authors report 30 chinese patients of ocular Lyme borreliosis, which is a tick-borne spirochaetal disease involving multiple organ systems. The ocular manifestations begin as conjunctivitis, and then as uveitis, choroidoretinitis, keratitis and vitritis. Diagnosis is based on case history and clinical and laboratory findings. Early cases may be cured by oral antibiotics while intravenous drip of large dosage is needed for advanced cases, with a relapsing rate of 16%. Prolonged systemic corticosteroids may predispose the patient to antibiotic failure; however, topical corticosteroids in combination with antibiotics may minimize ocular inflammation and complications.

Wrongful life: some of the problems.

The author considers that some of the reasonings used by both the American and English courts against recognising a wrongful life claim are far from persuasive. However, there may indeed be strong public policy reasons against judicial recognition of such a claim. If judicial remedy is not possible for children in wrongful life situations, society ought to assist them in the alleviation of some of the practical problems caused by deformities.

KIE: Liu reviews the history of several American and British wrongful life cases in which physicians were sued by or on the behalf of children born with handicaps. Generally courts have rejected these claims because of a reluctance to recognize that under some circumstances life itself can be an injury, and because of difficulties in assessing damages, fears of a flood of litigation, and concern over public policy implications. Liu finds some of these reasons unconvincing, but acknowledges that there may be sound public policy reasons for not accepting wrongful life claims. She suggests that court may not be the best forum for settling these disputes, and proposes a social security system to compensate handicapped children born because physicians were negligent in offering parents prenatal counseling and screening.