Background: Primary liver cancer, of which around 75–85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the “Health China 2030 Blueprint.”

During dermal injury and the associated trauma a number of compounds are released that can mediate the inflammatory response. Determining the cellular mechanisms that initiate the inflammatory responses to acute keratinocyte damage is important for understanding the regulation of epidermal inflammation. The recently cloned vanilloid receptor-1 (VR1) is a polymodal receptor, responding to thermal, pH, or vanilloids such as capsaicin stimulation. Although VR1 has been localized only on sensory neurons and within the central nervous system, recent evidence suggests a functional VR1 is expressed in human skin and epidermal cells. Using reverse transcription-polymerase chain reaction and immunoblotting we report that human keratinocytes and the human keratinocyte cell line HaCaT express VR1. Consistent with neuronal VR1, activation of epidermal VR1 by capsaicin induced a calcium influx. Treating HaCaT cells with capsaicin resulted in a dose-dependent expression of cyclooxygenase-2 (COX-2), whereas pretreatment with the VR1 receptor antagonist capsazepine abolished the capsaicin-stimulated increase in COX-2 expression. Furthermore, the capsaicin-induced expression of COX-2 was dependent on extracellular calcium. Activation of the epidermal VR1 by capsaicin also resulted in an increased release of interleukin-8 and prostaglandin E₂, and the stimulated release was attenuated by capsazepine. The finding that VR1 is expressed by keratinocytes is of great importance because it expands the putative role of VR1 beyond that of pain perception. Our results suggest that VR1 expression in keratinocytes may have a role in the inflammation that occurs secondary to epidermal damage or insult, and thus may function as a sensor for noxious cutaneous stimulation.

T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database. We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualization and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD. PIRD can be freely accessed at https://db.cngb.org/pird.

Objective: This meta-analysis was designed to explore the association between the systemic immune–inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & me... Plain language summary Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of many patients with advanced cancer. However, some patients still do not benefit from ICIs. Th...

William Isaacs and colleagues report evidence for a second prostate cancer risk locus in the HNF1B gene at 17q12, ∼26 kb from the previously reported risk locus in this region. The two loci are separated by a recombination hot spot and contribute independently to prostate cancer risk. We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, ∼26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 × 10−9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.

Objective T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations. Methods Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases. Results Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases. Conclusions These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.