Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide and is characterized by lymphocytic infiltration, elevated circulating autoantibodies, and proinflammatory cytokines. The key immune cell subset changes and the TCR/BCR repertoire alterations in pSS patients remain unclear. In this study, we sought to comprehensively characterize the transcriptional changes in PBMCs of pSS patients by single-cell RNA sequencing and single-cell V(D)J sequencing. Naive CD8⁺ T cells and mucosal-associated invariant T cells were markedly decreased but regulatory T cells were increased in pSS patients. There were a large number of differentially expressed genes shared by multiple subpopulations of T cells and B cells. Abnormal signaling pathways, including Ag processing and presentation, the BCR signaling pathway, the TCR signaling pathway, and Epstein–Barr virus infection, were highly enriched in pSS patients. Moreover, there were obvious differences in the CD30, FLT3, IFN-II, IL-1, IL-2, IL-6, IL-10, RESISTIN, TGF-β, TNF, and VEGF signaling networks between pSS patients and healthy controls. Single-cell TCR and BCR repertoire analysis showed that there was a lower diversity of T cells in pSS patients than in healthy controls; however, there was no significant difference in the degree of clonal expansion, CDR3 length distribution, or degree of sequence sharing. Notably, our results further emphasize the functional importance of αβ pairing in determining Ag specificity. In conclusion, our analysis provides a comprehensive single-cell map of gene expression and TCR/BCR profiles in pSS patients for a better understanding of the pathogenesis, diagnosis, and treatment of pSS. Key Points The proportions of immune cells and autoimmune and virus-related genes change in pSS. Cell communication of TGF-β and CD30 among immune cells was abnormal in pSS patients. Single-cell TCR and BCR repertoires do not change much in pSS patients.

The liver is one of vital organs of the human body, and it plays an important role in the metabolism and detoxification. Moreover, fetal liver is one of the hematopoietic places during ontogeny. Understanding how this complex organ develops during embryogenesis will yield insights into how functional liver replacement tissue can be engineered and how liver regeneration can be promoted. Here, we combine the advantages of single-cell RNA sequencing and Spatial Transcriptomics (ST) technology for unbiased analysis of fetal livers over developmental time from 8 post-conception weeks (PCW) and 17 PCW in humans. We systematically identified nine cell types, and defined the developmental pathways of the major cell types. The results showed that human fetal livers experienced blood rapid growth and immigration during the period studied in our experiments, and identified the differentially expressed genes, and metabolic changes in the developmental process of erythroid cells. In addition, we focus on the expression of liver disease related genes, and found that 17 genes published and linked to liver disease mainly expressed in megakaryocyte and endothelial, hardly expressed in any other cell types. Together, our findings provide a comprehensive and clear understanding of the differentiation processes of all main cell types in the human fetal livers, which may provide reference data and information for liver disease treatment and liver regeneration.

Background: The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China. Methods: Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results. Results: A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P < 0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+. Conclusion: The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.

Tumorigenesis and treatment are closely associated with various programmed cell death (PCD) patterns. However, the coregulatory role of multiple PCD patterns in colorectal cancer (CRC) remains unknown. In this study, we developed a multiple PCD index (MPCDI) based on 19 PCD patterns using two machine learning algorithms for risk stratification, prognostic prediction, construction of nomograms, immune cell infiltration analysis, and chemotherapeutic drug sensitivity analysis. As a result, in the TCGA-COAD, GSE17536, and GSE29621 cohorts, the MPCDI can effectively distinguished survival outcomes in CRC patients and served as an independent factor for CRC patients. We then explored the immune infiltration landscape in two groups using the nine algorithms and found more overall immune infiltration in the high-MPCDI group. TIDE scores suggested that the increased immune evasion potential and immune checkpoint inhibition therapy may be less effective in the high-MPCDI group. Immunophenoscores indicated that anti-PD1, anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4), and anti-PD1-CTLA4 combination therapies are less effective in the high-MPCDI group. In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.