Burden of All Cancers Along With Attributable Risk Factors in China From 1990 to 2019: Comparison With Japan, European Union, and USA.

Background: Understanding the epidemiological characteristics of various cancers can optimize the prevention and control strategies in the national cancer control plan. This study aimed to report the burden differences, pattern trend, and potential risk factors of all neoplasm types in China in recent 30 years, and further compared with top economies in the world. Methods: The disability-adjusted life-years (DALYs) and age-standardized DALY rate (ASDR) of all neoplasms with the attributable risk factors from 1990 to 2019 in China, Japan, European Union, USA, and the world were extracted from the Global Burden of Disease Study 2019. The temporal trend analysis was estimated using the joinpoint regression model. Results: In 2019, about 251.4 million DALYs worldwide were caused by all neoplasms, and nearly 26.9% (67.5 million DALYs) occurred in China with the ASDR in 2019 of 342.09/10 000, which was higher than European Union (334.25/10 000), USA (322.94/10 000), and Japan (250.36/10 000). Although the cancer burden of the colorectum, non-Hodgkin lymphoma, oral cavity, ovary, and kidney in China was lower than in Japan, European Union and USA, the corresponding ASDR gradually increased in China over the past 30 years, but declined in the three developed areas. Around 46.29% of overall neoplasms DALYs in China in 2019 were attributed to 22 identified risk factors, and the specific risk attributable-fraction for several neoplasm types varied greatly in these regions. Conclusion: The ASDR of cancers of the lung, colorectum, pancreas, non-Hodgkin lymphoma, oral cavity, ovary, kidney, and chronic lymphoid leukemia increased in China compared to 30 years ago. With the population aging and the social transformation in China, the increasing burden of neoplasms and the changing spectrum of neoplasms suggest that effective comprehensive prevention and treatment measures should be adopted to reduce the burden, including public health education, strict tobacco-control policy, healthier lifestyles, along with expanding vaccination programs and early cancer screening.

Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion.

BACKGROUND: Motion sickness (MS) is a disease that occurs during unbalanced movement, characterized by gastrointestinal symptoms and autonomic nervous system activation. Current clinical treatments for MS are limited. Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance. In the present study, mesenchymal stem cells (MSCs) have been shown to exert strong immuno-suppressive effects. AIM: To explore whether umbilical cord-derived mesenchymal stem cells (UC-MSCs) can prevent the occurrence of MS, and the underlying mechanism regulated by MSCs in a mouse model of MS. METHODS: A total of 144 (equal numbers of males and females) 5wkold BALB/c mice were randomly divided into five groups: Normal group (n = 16), MS group (n = 32), MSCs group (n = 32), MS + MSCs group (n = 32), and MS + AS101/MSCs group (n = 32). The MSCs group (n = 32), MS + MSCs group (n = 32), and MS + AS101/MSCs group (n = 32) were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs (1 × 106 cells/mouse). Mice in the MS (n = 32), MS + MSCs, and MS + AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8 × g/min for MS model establishment on days 3, 5, 8, and 10 after UC-MSCs injection. The Morris water maze (MWM) test was used to observe the symptom of dizziness. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples. Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues. Histological examination was performed by hematoxylin and eosin (HE) staining for conventional morphological evaluation in the petrous part of temporal bone samples. RESULTS: The MWM test demonstrated that UC-MSCs improved the symptoms of MS. The MS + MSCs group was faster than the MS group on days 3 and 5 (P = 0.036 and P = 0.002, respectively). ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10 (IL-10) in the cochlear tissues were increased after transplantation with UC-MSCs (MS + MSCs group vs MS group at 3 and 5 d, P = 0.002 and c P < 0.001, respectively). RT-qPCR results confirmed a significant increase in IL-10 levels at four time points (MS + MSCs group vs MS group, P = 0.009, P = 0.009, P = 0.048, and P = 0.049, respectively). This suggested that UC-MSCs reduced the sensitivity of the vestibular microenvironment by secreting IL-10. Moreover, Western blot analysis showed that the MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues. The levels of IL-10, IL-10RA, JAK2, STAT3, and phosphorylated JAK2 and STAT3 in the MS + MSCs group were increased compared to those of the MS group (P < 0.05). The morphological changes in the four groups showed no significant differences. The role of IL-10 secretion on the ability of UC-MSCs to successfully improve the symptoms of MS was confirmed by the diminished therapeutic effects associated with treatment with the IL-10 inhibitor ammonium trichloro (dioxoethylene-o,o') tellurate (AS101). CONCLUSION: Prophylactic transplantation of UC-MSCs can alleviate the clinical symptoms of MS in mice, particularly at 3-5 d after preventive transplantation. The mechanism for UC-MSCs to reduce the sensitivity of vestibular cortex imbalance may be the secretion of IL-10. The next step is to demonstrate the possibility of curing MS in the vestibular environment by intermittent transplantation of MSCs. Above all, MSCs are expected to become a new method for the clinical prevention and treatment of MS.

Validation of laser scanning confocal microscopy as a diagnostic method for lymphedema using a rat model.

Most previous diagnostic methods for lymphedema are invasive. Laser scanning confocal microscopy (LSCM) combines laser and computer image processing technology, is capable of increasing the resolution of optical microscopy by 30-40%, and boasts a comparable resolution to that of histological examination. We constructed the rat tail lymphedema model to simulate secondary lymphedema and to validate the noninvasive technique of in vivo reflectance LSCM for the diagnosis of lymphedema. The rat tail lymphedema model was constructed by cutting and ligating the lymphatic vessels in the rat tail. Lymphedema in the postoperative rat tail was assessed by a comprehensive range of methods including the change of rat tail diameter, lymphocytic radionuclide imaging, LSCM, and immunohistochemistry using a specific lymphatic vessel marker, prospero homeobox protein 1 (PROX1). The noninvasive LSCM method along with other techniques validated the rat tail lymphedema model. LSCM was used to perform qualitative and quantitative evaluation of the state and extent of lymphedema in the rat tail model. Receiver operating characteristic (ROC) curve analysis, which provided an area under the curve (AUC) value of 0.861, supported the feasibility of using LSCM as a reliable diagnostic technique for lymphedema. The rat tail lymphedema model can be successfully constructed by cutting and ligating the lymphatic vessels in the rat tail. Although LSCM cannot replace the method of skin biopsy examination, it offers a painless and noninvasive alternative for diagnosing lymphedema. Thus, LSCM can potentially be adopted in clinical practice as a supporting method to be used in combination with other techniques.

N6-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN/TMEM127 and promotes sensitivity to everolimus in gastric cancer.

N6-methyladenosine (m6A) is the most common epigenetic RNA modification with essential roles in cancer progression. However, roles of m6A and its regulator METTL3 on non-coding RNA in gastric cancer are unknown. In this study, we found elevated levels of m6A and METTL3 in gastric cancer. Increased METTL3 expression indicated poor outcomes of patients and high malignancy in vitro and in vivo. Mechanically, m6A facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an m6A/DGCR8-dependent mechanism. The m6A modification that mediated this process occurred on the A879 locus of pri-miR-17-92. The miR-17-92 cluster activated the AKT/mTOR pathway by targeting PTEN or TMEM127. Compared with those with low levels of METTL3, METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus. These results reveal a perspective on epigenetic regulations of non-coding RNA in gastric cancer progression and provide a theoretical rationale for use of everolimus in the treatment of m6A/METTL3-high gastric cancer.

The Effects of High-Salt Gastric Intake on the Composition of the Intestinal Microbiota in Wistar Rats.

BACKGROUND A high-salt diet may result in chronic disease and changes in the intestinal microbiota. This pilot study aimed to investigate the microbial composition of the intestine in Wistar rats given intragastric high-salt infusions for four weeks. MATERIAL AND METHODS Six 4-week-old male Wistar rats were fed standard chow and divided into the high-salt group (n=3) and the control study group (n=3). Rats in the high-salt group were given 1 ml of 10% NaCl solution intragastrically three times per week for four weeks. The fecal pellets were collected, and the microbiota was characterized using 16S rRNA gene sequencing that targeted the V4 region. The relative abundance of microbial populations was compared using linear discriminant analysis effect size (LEfSe) statistical analysis for the identification of biomarkers between two or more groups, principal component analysis (PCA), and linear discriminant analysis (LDA). Microbial genome prediction was performed using the phylogenetic investigation of communities by reconstructing the unobserved states (PICRUSt) bioinformatics software. RESULTS There was no significant difference in the alpha diversity of the fecal microbiota between the high-salt group and the control group. However, PCA showed structural segregation between the two groups. Further analysis using LEfSe showed that the intestinal contents in the high-salt group had significantly reduced populations of Lactobacillus and Prevotella NK3B31, and a significant increase in Alloprevotella and Prevotella 9, without physiological or pathological changes. CONCLUSIONS A pilot study in Wistar rats showed that high-salt intake was associated with a change in the composition of the intestinal microbiota.

CD148 Serves as a Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Dephosphorylating EGFR.

CD148 is a member of the receptor-type protein tyrosine phosphatase family encoded by the PTPRJ gene and has controversial impacts on cancers. In this study, we investigated the clinical significance of CD148 in gastric cancer and the possible mechanisms. Suppressed CD148 expression indicated adverse pathological features and poor outcomes in gastric cancer patients. CD148 overexpression impeded tumor proliferation, motility, and invasiveness, while CD148 knock-down or knockout promoted the ability of gastric cancer cells to grow and metastasize in vitro and in vivo. Mechanistically, CD148 negatively regulated EGFR phosphorylation of multiple tyrosine residues, including Y1173, Y1068, and Y1092, and remarkably inhibited downstream PI3K/AKT and MEK/ERK pathways. In silico analysis revealed that gene deletions or missense/truncated mutations of PTPRJ gene rarely occurred in gastric cancers. Instead, a 3' UTR-specific methylation might regulate CD148 expression, and the potential regulators were TET2 and TET3. Collectively, our results suggest that CD148 is a convincing prognostic marker as well as a potential therapeutic target for gastric cancer.

Identification of Wohlfahrtiimonas chitiniclastica isolated from an infected cow with hoof fetlow, China.

Wohlfahrtiimonas chitiniclastica is a rare but an emerging zoonotic pathogen. Here, we report the isolation and identification of W. chitiniclastica strain DZ2015 from hoof pus of an infected cow with hoof fetlow in Shandong, China by 16S rRNA gene sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing and mouse infection experiments showed that the strain of W. chitiniclastica had broad susceptibility and was pathogenic to mice. This is the first report of the W. chitiniclastica isolated from an infected domestic animal in China.