Huina Zhang

Abstract Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8 + T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC that has HER2 immunohistochemical (IHC) score of 1+ or score of 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating this group of tumors. Trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC was recently approved by the U.S. Food and Drug Administration as the first targeted therapy to treat HER2-low BC. However, HER2-low BC is still not well characterized clinically and pathologically. This review aims to update the current biological, pathological and clinical landscape of HER2-low BC based on the English literature published in the past two years and to propose the future directions on clinical management, pathology practice, and translational research in this subset of BC. We hope it would help better understand the tumor biology of HER2-low BC and the current efforts for identifying and treating this newly recognized targetable group of BC.

Abstract Background Ganoderma lucidum , a double-walled basidiospore produced by porous basidiomycete fungi, has been used as a traditional medicine for thousands of years. It is considered a valuable Chinese medicine for strengthening body resistance, invigorating the spleen, and replenishing Qi. G. lucidum contains a variety of active ingredients, such as polysaccharides, triterpenoids, nucleosides, sterols, alkaloids, polypeptides, fatty acids, steroids, and inorganic elements, and has anticancer, anti-inflammatory, hepatoprotection, hypoglycemic, anti-melanogenesis, anti-aging, and skin barrier-repairing activity. Conclusions The review summarizes the traditional usages, distribution, active constituents, structure, and biological effects of G. lucidum , with an aim to offer directions for further research and better usage of G. lucidum as a medicinal raw material.

Mesenchymal stem cells (MSCs) are one of the most widely clinically trialed stem cells, due to their abilities to differentiate into multiple cell lineages, to secrete regenerative/rejuvenative factors, and to modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSCs from 32 donors and revealed donor-dependent variations in two non-correlated properties, (1) cell proliferation, and (2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSCs. Through unbiased transcriptomic analyses, we discovered that IFN-γ and NF-κB signaling were positively associated with immune modulatory function of MSCs. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while having abolished donor-dependent variations in immune modulatory function, did not overall make different donor-derived MSCs the same at whole transcriptomic levels, demonstrating that the cells were still different in many other biological perspectives, and may not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to ensure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSCs to treat inflammation-related clinical conditions and/or autoimmune diseases.