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We compared chromosomal mosaicism, detected by next-generation sequencing (NGS), during preimplantation genetic testing (PGT) with that detected by single-nucleotide polymorphism (SNP) array-based PGT to assess the pregnancy outcomes associated with both platforms in a retrospective cohort study of patients undergoing in vitro fertilization in a single university-based assisted reproduction center. In total, 6427 blastocysts biopsied from 1513 patients who underwent 2833 oocyte retrievals from January 2017 to February 2019 were identified. The incidence of mosaicism was significantly higher in the NGS-based PGT group than in the SNP array-based PGT group. Furthermore, some aneuploid specimens were affected by mosaicism. The total mosaicism detection rate with NGS-based PGT (23.3%) was significantly higher than that with SNP array-based PGT (7.7%). Mosaicism rates were similar when stratified by maternal age or PGT type. The SNP array cohort showed a significantly higher spontaneous abortion rate than the NGS cohort (10.07% versus 6.33%; P = 0.0403). The ongoing pregnancy/live birth rate was higher in the NGS cohort (44.1%) than in the SNP array cohort (42.28%). Our results confirm that NGS-based PGT can detect mosaicism more frequently than SNP array-based PGT in trophectoderm specimens. Therefore, clinical application of NGS for PGT may improve pregnancy outcomes compared with that of SNP array-based PGT. More detailed blastocyst detection and classification is necessary to prioritize embryo transfers., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the beneficial and adverse effects of Wendan Decoction (温胆汤, WDD) for the treatment of schizophrenia., Methods: Five electronic databases were searched until May 2014, including the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientist Journal Database, PubMed, and the Cochrane Central Register of Controlled Trials in the Cochrane Library. The randomized controlled trials (RCTs) testing WDD against placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against antipsychotic drugs alone were included. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards., Results: Thirteen RCTs (involving 1,174 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that WDD combined with antipsychotic drugs were more effective in clinical comprehensive effect, Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone. However, WDD had less effectiveness compared with antipsychotics in clinical comprehensive effect; and WDD was not different from antipsychotic drugs for PANSS scores. The side effects were significantly reduced in the intervention group compared with the control group., Conclusions: WDD appears to be effective on improving symptoms in patients with schizophrenia. However, due to poor methodological quality in the majority of the included trials, the potential benefit from WDD needs to be confirmed in rigorous trials and the design and reporting of trials should follow the international standards.

Objective: To investigate the role of tazarotene induced gene-2 (TIG2) in psoriasis vulgaris., Methods: TIG2 protein and mRNA expressions in normal tissues, psoriatic lesions and uninvolved skin tissues were detected by immunohistochemistry and in situ hybridization, respectively., Results: TIG2 protein and mRNA were expressed in all the layers of normal and uninvolved epidermis. TIG2 expression was detected in the upper layers of the stratum spinosum of the marginal region of the psoriatic lesions, but not in the central area of the lesions. TIG2 expression was significantly lower in the basal layers of the central area of the paoriasis than that in the normal skin and uninvolved tissues (P < 0.01), and also lower in the marginal regions of the lesions (P < 0.01).The suprabasal layers of the marginal region in the lesion showed significantly lower TIG2 expression than the central area of the lesion (P < 0.01)., Conclusion: TIG2 may maintain the normal differentiation of epidermal keratinocytes and implicate in the pathogenesis and development of psoriasis vulgaris.

T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with cells carrying the DR1 antigen. After priming, T cells proliferated in response to both DR1-positive-stimulating cells and a peptide derived from a polymorphic region of the HLA-DR beta 1*0101 chain presented by responder's antigen-presenting cells (APC). The dominant epitope recognized by the primed T cells corresponded to residue 21-42 and was presented by the responder's HLA-DR12 antigen. The DR1 peptide-reactive T cells express T cell receptor V beta 3. The results demonstrate that allopeptides derived from the processing and presentation of donor major histocompatibility complex molecules by host-derived APC trigger alloreactivity. The frequency of T cells engaged in the indirect pathway of allorecognition is about 100-fold lower than that of T cells participating in the direct recognition of native HLA-DR antigen. However, indirect allorecognition may play an important role in chronic allograft rejection, a phenomenon that is mediated by the activation of T helper cells and of alloantibody-producing B cells.

T cell reactivity to alloantigens results from direct and indirect recognition of allogeneic MHC molecules and/or peptides. Although direct recognition is not self-MHC restricted, indirect recognition, the result of alloantigen processing and presentation by host APC, is restricted by the self (responder) MHC molecule to which the allopeptide has bound. We have studied the MHC restriction and TCR usage in T cell alloreactivity to a synthetic peptide corresponding to amino acid residues 21-42 of the DR beta 1*0101 molecule. T cell lines were developed by in vitro immunization of T cells from three responders carrying the DR beta 1*1101 allele with this peptide. In all three responders, reactivity to peptide 21-42 was restricted by the DR11 molecule. A limited usage of V beta genes was found in these T cell lines, all of which shared the expression of V beta 13.2. Because indirect recognition of allopeptide may play an important role in chronic, antibody-mediated allograft rejection, study of the TCR gene usage may contribute to the development of specific immunosuppression therapy.

It has been suggested that self major histocompatibility complex (MHC) peptides bound to self MHC molecules may be involved in the intrathymic induction of self tolerance. We studied the antigenicity of synthetic peptides derived from the first domain of DR beta 1*0101 chain in a DR beta 1*0101 responder. We found that a peptide corresponding to residues 21-42 of the beta chain could elicit the proliferation of autoreactive T cells. A T cell line (TCL-SUN) and 7 of 9 T cell clones (TCC) derived from TCL-SUN specifically recognized peptide 21-42 in the presence of APCs carrying the DR beta 1*0101 allele. DR beta 1*0101 positive APCs stimulated the TCCs in the absence of peptide, although the magnitude of the response was much lower than in cultures with peptide. This suggests that self DR1 molecules are continuously processed into peptides that are presented by the DR1 molecules on the surface of the cells. The data indicate that some T cells whose TCR binds to self MHC peptides presented by self MHC molecules are not deleted, although their ligand is continuously present. TCCs specific for peptide 21-42 presented in the context of DR1 were also stimulated by cells heterozygous for DR beta 1*0301 and 1601, indicating that some DR peptide-specific autoreactive T cells participate in alloreactivity.

The results of a combined immunocytochemical, morphometric, and clinicopathologic analysis of growth-hormone-producing and prolactin-producing pituitary cells in 28 subjects ranging in age from 16 to 90 are reported. There was a significant age-related decline in the number and size of growth-hormone-producing cells, which was most marked in the transition from youth to middle age. There was also a significant age-related decline in the number of pituitary parenchymal cells but not in pituitary weight. Prolactin cells did not show a significant decline in number with age.

A case of primary neuroendocrine carcinoma in an unusual location, the liver, is reported. The neoplasm was composed of small, uniform cells that had distinct borders and grew in strands, ribbons and nests; its appearance resembled that of a carcinoid. Electron microscopy and special staining of the neoplastic cells confirmed the neuroendocrine nature of the tumor, and the cells showed immunoreactivity for gastrin and pancreatic polypeptide by the PAP. The recent literature is reviewed, and the possible histogenesis of hepatic neuroendocrine carcinoma is discussed.

Ultraviolet-induced unscheduled DNA synthesis (i.e. repair synthesis) in human epidermal cells was measured as a function of age. Normal mammary skin specimens were obtained at surgery from 36 female patients, ranging in age from 17 to 77 years. The enzymatically isolated epidermal cells were analyzed for two parameters: (1) the number and percentage of cells carrying out repair synthesis, and (2) the rate of ultraviolet-induced unscheduled thymidine incorporation in individual cells. The results show that the percentage of epidermal cells capable of DNA excision repair synthesis does not decrease significantly with age, but that the rate of unscheduled DNA synthesis in individual cells decreases to a highly significant degree with advancing age.

Histologic and ultrastructural changes of the liver in old and non-old Wistar rats and the effects due to persistent restriction of food and exposure to noise were studied. There was increase of hepatocytes with enlarged or double nuclei, and apoptosis as well as fatty change of the liver in the old rats. The incidence of apoptosis and fatty change was lower in those rats with persistent food restriction, but no significant change of the liver was seen in those animals persistently exposed to noisy, environment.

Basement membranes were studied in the seminiferous tubules of the male, and capillaries of the pectoralis muscles in "normal" males and females. Age-related changes in basement membrane thickness were investigated on electromicrographs by quantitative morphometry. Specimens obtained from either autopsies or surgical procedures were divided into four different age groups ranging from age 16 to age 87 years. The results show a statistically significant increase in the basement membrane thickness correlated with age, in basement membranes associated with both mesenchymal (capillaries) and epithelial (testes) tissue. A comparison of capillary basement membrane in the pectoralis muscle and seminiferous tubule basement membrane in the male show a constant increase in thickness until the age of 60 years, following which only slight increases were noted. The basement membrane thickness in capillaries of the pectoralis muscle in females showed linear increases throughout the lifespan, although at a lower rate than in the male; at age 80 years, it had the same thickness as the male. A comparison of basement membrane thickness between the youngest and oldest groups showed an increase of approximately 50% in all tissues studied.