Background: The incidence of colorectal cancer is high and on the rise. The genetic and protein expressions of RUNT-associated transcription factor 3 (RUNX3) and human epidermal growth factor receptor 2 (HER2) in colorectal cancer (CRC) and adjacent normal tissues were detected to preliminarily explore their correlation and clinical significance.Methods: CRC specimens excised during general surgery were selected for localization and quantitative analysis of protein and gene expression by SP (Streptavidin-peroxidase conjugated method) immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. Combined with the patients' data, the relationship between the expression of the two genes and tumor characteristics was analyzed. Log-rank test was used to analyze the correlation between the two proteins and survival prognosis of CRC patients. The expression of RUNX3 in RKO and HCT-116 was knocked down, and the relative expression of HER2 in the two cell lines was detected.Results: Immunohistochemical, RT-qPCR and Western blot results showed that the positive expression rate of RUNX3 in CRC was lower than in the normal group, and HER2 in CRC was higher than in the normal group. The positive expression of the two proteins correlated with the pT and pN stages of CRC. A significant negative correlation between the expression of the two genes in CRC. Follow-up results showed that the number of Runx3-positive patients was higher than negative ones, while HER2 positive were fewer than negative ones. In vitro experiments showed that RUNX3 protein and gene expression decreased, HER2 protein and gene expression increased in RUNX3 knockdown RKO and HCT-116 cells, respectively (P<0.05). Conclusions:The expression of RUNX3 and HER2 in CRC is related to the occurrence and development of CRC, and the two genes have a negative regulating effect.

Background: This study sought to review colorectal cancer liver metastasis (CRLM) patients at multiple centers to analyze the factors affecting the success of conversion therapy in patients whose CRLM was initially evaluated as potentially resectable, to explore the effect of different treatment approaches on patient survival, and to provide a scientific reference for clinical treatment of CRLM.Methods: Fifty patients whose CRLM was initially evaluated as potentially resectable at 3 large Chinese general hospitals were enrolled in this retrospective study. Statistical analyses were carried out on the general data and pathological characteristic data to examine the clinical efficacy of the treatment approaches. The factors affecting the success of conversion therapy were analyzed by logistic regression. Additionally, followup appointments were conducted to examine survival, and survival curves were plotted using the Kaplan-Meier estimator. The effect of different clinical and pathological characteristics on CRLM patients was analyzed.Results: Seventeen patients achieved no evidence of disease (NED) status through surgical resection/ ablation after undergoing conversion therapy. The multifactor analysis demonstrated that the number of liver metastases was the primary risk factor affecting the efficacy of conversion therapy (P<0.05). Survival analysis results showed statistically significant difference in overall survival (OS) between the NED group and the inconspicuous/progressive group (P<0.0001). Also, there was a statistically significant difference in the progression-free survival (PFS) between the NED group and the inconspicuous/progressive group (P<0.0001). Patients in the surgical resection group had better OS and PFS than those in the ablation group (P<0.0001 and P<0.01, respectively). The monofactor analysis demonstrated that the number and maximum diameter of liver metastases, serum Carcino-Embryonic Antigen (CEA) level, and BRAF V600E mutation status were factors affecting the OS of CRLM patients (P<0.05), of which BRAF V600E mutation was the primary determinant (P<0.05).Conclusions: Among the patients whose CRLM was initially evaluated as unresectable, those who underwent surgical resection of the primary lesions and liver metastases after receiving conversion therapy had the best prognosis. Thus, a thorough evaluation should be conducted to determine the effect of and survival factors affecting conversion therapy in the treatment of liver metastases.

Hennekam Lymphangiectasia–Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.

The COVID-19 rapidly evolved into a global pandemic. Countries have taken measures widely to prevent and control the epidemic. China for example, has control the spread effectively, while many countries are still striving to cope with the increasing COVID-19 confirmed cases. The epidemic revealed serious problems of public health governance in many countries with long lasting social and economic consequences. This commentary reviews the pandemic response measures in five selected countries: China, Italy, the United States, Brazil and India. Building on critical reflections on the problems incurred in each country's pandemic responses, we provide a theoretical framework to reconceptualize public health as multiple types of economic goods. We further couple this reconceptualization with a systems approach to public health and wellbeing to offer new thinking on health governance. Finally, we propose suggestions for better, preventative and comprehensive epidemic prevention and health governance in an increasing urban future.