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Liver metastasis is a major cause of death in gastric cancer patients, but the underlying mechanisms are poorly understood. Through a combination of in vivo screening and transcriptome profiling followed by quantitative RT-PCR and tissue array analyses, we found that mitogen-activated protein kinase 4 (MAPK4) downregulation in gastric cancer tissues from patients is significantly associated with liver metastasis and poor prognosis. The knockdown of MAPK4 in gastric cancer cells promotes liver metastasis in orthotopic mouse models. MAPK4 depletion in gastric cancer cells induces the secretion of macrophage migration inhibitory factor (MIF) to polarize tumor-associated macrophages (TAMs) in orthotopic xenograft tumors. Moreover, TAMs activate epithelial–mesenchymal transition of gastric cancer cells to suppress MAPK4 expression, which further increases MIF secretion to polarize TAMs. Taken together, our results suggest a previously undescribed positive feedback loop between cancer cells and macrophages mediated by MAPK4 silencing that facilitates gastric cancer liver metastasis.

Purpose This study described a case with carbohydrate sulfotransferase 3 (CHST3) spondyloepiphyseal dysplasia and summarized all previously reported cases with CHST3-related skeletal dysplasia. Methods A 14.8-year-old boy underwent clinical and radiological evaluations, including high-resolution peripheral quantitative computed tomography. The patient and the family members underwent genetic tests. All CHST3-related skeletal dysplasia cases from PubMed and Embase were collected and analysed. Results The proband was found to have short lower limbs during a prenatal examination. At 11 years old, he had a compression fracture of L2. Since 13 years of age, he has complained of aggravated pain in the large joints. Physical examination showed a height Z score of -4.94, short limbs, and restricted movement of the elbows and knees. X-rays showed epiphyseal dysplasia of the carpal bones, enlargement of the left elbow and knee joints, and subluxation of the left hip. Echocardiography showed abnormal cardiac valves. Compared with the norm, his total and trabecular volumetric bone mineral density (vBMD) were significantly lower, and the microarchitecture of the trabecular bone was poor at the distal radius and tibia. Two novel missense variants of c.1343T > G and c.761C > G in CHST3 were inherited from his father and mother, respectively. In the systematic review, short stature, limited joint extension, joint pain, and joint dislocation were the most common characteristics associated with mutations of CHST3. Over 90% of pathogenic variants are located in the sulfotransferase domain. Conclusion This patient with CHST3-related skeletal dysplasia has progressive joint pain and movement restriction, poor vBMD, and abnormalities of the microarchitecture of the trabecular bone. There is no apparent genotype-phenotype correlation in this disorder.

Objective This study aimed to explore the effects of tea polyphenols (TP) on inflammation of orbital fibroblasts in Graves’ ophthalmopathy (GO) and to provide new ideas for GO treatment. Methods Primary orbital fibroblasts were extracted from orbital adipose/connective tissues of patients with and without GO. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of interleukin (IL)-6, IL-1β, and monocyte chemotactic protein (MCP)-1 in non-GO and GO orbital fibroblasts. The CCK-8 assay was used to determine the appropriate concentration of TP for subsequent experiments. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the effects of TP on lipopolysaccharide (LPS)-induced production of inflammatory cytokines. Nuclear factor-κB (NF-κB) expression was measured using Western blotting analysis. NOD-like receptor 3 (NLRP3) expression was detected using both Western blotting analysis and immunofluorescence staining. Results The mRNA levels of IL-6, IL-1β, and MCP-1 in GO orbital fibroblasts were significantly higher than those in non-GO cells. TP treatment significantly inhibited LPS-induced production of inflammatory factors, including IL-6, IL-1β, and MCP-1. TP also inhibited the expression levels of NF-κB and NLRP3. Inflammation in the GO orbital fibroblasts was higher than that in non-GO cells. TP inhibited the production of inflammatory cytokines in GO orbital fibroblasts in vitro through the NF-κB/NLRP3 pathway. Conclusion These findings suggest that TP may have a potential role in GO treatment.

Retrospective epidemiological study.To determine the characteristics of sports-related spinal cord injury (SCI) in China and assess changes in the trend of these injuries that may impact policy making.China Rehabilitation Research Center (CRRC), Beijing.Of the 2448 SCI cases reviewed, 6.7% (n = 164) were caused by sport- and recreation-related accidents. They were admitted to the CRRC between January 1, 2013 and December 31, 2019. We collected data on age, sex, etiology, the neurological level of injury, the American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores on admission, and the neurological recovery results at discharge.Dancing (58.6%), followed by water sports (14.7%) and taekwondo (4.2%) were the leading etiologies. Of the SCIs caused by dancing, 27.1% of the individuals had incomplete injury, and of these, 57.7% showed improved neurological function. However, 72.9% had complete injury, and these individuals did not show any improvement in neurological function. Individuals with dance-related SCIs graded as A and D according to the AIS, showed no significant improvement in their motor function scores at the time of discharge. While the scores of those graded B and C increased significantly, there were no significant differences in the light touch and pin touch scores.The etiology of sports-related SCI in China has changed dramatically, with dancing replacing water sports as the primary cause of SCIs. Individuals with dance-related SCIs have a poor prognosis. In China, prevention of dance-related SCIs has become a priority.