BackgroundSystemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states.MethodsWe reviewed 160 patients with HCC treated with TKIs and ICIs. The patients’ psoas muscle size was measured on axial computed tomography scans and normalized for the patients’ height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients’ clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated.ResultsSarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group.ConclusionSarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

BackgroundBeta-2-microglobulin (B2M), a light chain subunit of the major histocompatibility complex (MHC) class I complex, has been implicated in tumorigenesis. However, whether it is expressed in different epithelial-type ovarian tumours remains unknown. This study was performed to examine the expression of B2M in different histopathological types of ovarian tumours, to explore the function of B2M in ovarian cancer (OC) cells and to investigate the mechanisms underlying the regulation of B2M by the TGF-β signaling pathway.MethodsB2M expression in normal ovarian tissues and epithelia-type ovarian tumours was detected by immunohistochemistry and Western blot, followed by the analysis of association with clinical features. OC cells were transfected with B2M-siRNA and cell proliferation, migration and invasion were determined by WST-1 assay, wound healing assay and Transwell invasion assay, respectively. The regulation of B2M by the TGF-β signaling pathway in OC cells was examined by Western blot, ELISA and qRT-PCR.ResultsWe found that B2M was overexpressed in ovarian borderline and malignant tumours compared with benign tumours and normal controls, but was not associated with age, tumour size, lymph node metastasis and clinical stage. Knocking down of B2M led to a decrease in OC cell proliferation, migration and invasion. The expression of B2M was downregulated by TGF-β1 in OC cells, which was abolished in the presence of the inhibitor of TGF-β type I receptor.ConclusionOur findings suggest that B2M is a potential tissue biomarker and therapeutic target of borderline and malignant ovarian tumours and the dysregulation of B2M in these tumours may be mediated by the TGF-β signaling pathway.

As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.

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Parkinson’s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in PD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70 PINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression remains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using switching mechanism at 5’end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of the translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion analysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-binding sites within the PINK1 promoter were identified. NFκB overexpression led to the up-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a strong activator of NFκB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly suggested that PINK1 expression is tightly regulated at its transcription level and NFκB is a positive regulator for PINK1 expression.